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In rats and primates, the central nucleus of the amygdala (CeN) is most known for its role in responses to fear stimuli. Recent evidence also shows that the CeN is required for directing attention and behaviors when the salience of competing stimuli is in flux. To examine how information flows through this key output region of the primate amygdala, we first placed small injections of retrograde tracers into the subdivisions of the central nucleus in Old world primates, and examined inputs from specific amygdaloid nuclei. The amygdalostriatal area and interstitial nucleus of the posterior limb of the anterior commissure (IPAC) were distinguished from the CeN using histochemical markers, and projections to these regions were also described. As expected, the basal nucleus and accessory basal nucleus are the main afferent connections of the central nucleus and transition zones. The medial subdivision of the central nucleus (CeM) receives a significantly stronger input from all regions compared to the lateral core subdivision (CeLcn). The corticoamygdaloid transition zone (a zone of confluence of the medial parvicellular basal nucleus, paralaminar nucleus, and the sulcal periamygdaloid cortex) provides the main input to the CeLcn. The IPAC and amygdalostriatal area can be divided in medial and lateral subregions, and receive input from the basal and accessory basal nucleus, with differential inputs according to subdivision. The piriform cortex and lateral nucleus, two important sensory interfaces, send projections to the transition zones. In sum, the CeM receives broad inputs from the entire amygdala, whereas the CeLcn receives more restricted inputs from the relatively undifferentiated corticoamygdaloid transition region. Like the CeN, the transition zones receive most of their input from the basal nucleus and accessory basal nucleus, however, inputs from the piriform cortex and lateral nucleus, and a lack of input from the parvicellular accessory basal nucleus, are distinguishing afferent features.

Though both the amygdala and the serotonin system appear to play critical roles in regulating fear and anxiety, little is known regarding the organization of serotonergic inputs to the primate amygdala. The present study employed immunohistochemistry to determine the distribution of serotonin fibers in the macaque amygdala. The brains of three adult male Macaca fascicularis monkeys were prepared for histological analysis using a polyclonal antibody to serotonin. The macaque amygdala is densely innervated by serotonergic fibers and demonstrates a distinctive pattern of fiber distribution and density among the 13 nuclei and cortical areas. The highest density of 5-hydroxytryptamine immunoreactive fibers is observed in the central nucleus, the nucleus of the lateral olfactory tract, the paralaminar nucleus, the anterior amygdaloid area and a small region of the amygdalohippocampal area. Moderate fiber densities are found in portions of the basal, lateral, and intercalated nuclei. The lowest fiber densities are observed in the accessory basal, posterior cortical, anterior cortical and medial nuclei, and in subregions of the periamygdaloid cortex. The present study provides evidence that the serotonergic system can have substantial influence on the ongoing activity of the amygdaloid complex.

Projections from the amygdala to the piriform cortex are proposed to provide a pathway via which the emotional system can modulate the processing of olfactory information as well as mediate the spread of seizure activity in epilepsy. To understand the details of the distribution and topography of these projections, we injected the anterograde tracer Phaseolus vulgaris-leucoagglutinin into different nuclear divisions of the amygdaloid complex in 101 rats and analyzed the distribution and density of projections in immunohistochemically processed preparations. The heaviest projections from the amygdala to the piriform cortex originated in the medial division of the lateral nucleus, the periamygdaloid and sulcal subfields of the periamygdaloid cortex, and the posterior cortical nucleus. The heaviest terminal labeling was observed in layers Ib and III of the medial aspect of the posterior piriform cortex. Lighter projections to the posterior piriform cortex originated in the dorsolateral division of the lateral nucleus, the magnocellular and parvicellular divisions of the basal and accessory basal nuclei, and the anterior cortical nucleus. The projections to the anterior piriform cortex were light and originated in the dorsolateral and medial divisions of the lateral nucleus, the magnocellular division of the basal and accessory basal nuclei, the anterior and posterior cortical nuclei, and the periamygdaloid subfield of the periamygdaloid cortex. The results indicate that only selective amygdaloid nuclei or their subdivisions project to the piriform cortex. In addition, substantial projections from several amygdaloid nuclei converge in the medial aspect of the posterior piriform cortex. Via these projections, the amygdaloid complex can modulate the processing of olfactory information in the piriform cortex. In pathologic conditions such as epilepsy, these connections might provide pathways for the spread of seizure activity from the amygdala to extra-amygdaloid regions. J. Comp. Neurol. 476:414–428, 2004. © 2004 Wiley-Liss, Inc.

We have previously described the origins of neocortical inputs to the lateral nucleus of the macaque monkey amygdala based on retrograde tracing studies. Here we report results from studies that have attempted to confirm the projections from several candidate afferent regions using (3)H-amino acid autoradiography as an anterograde tracer. We have charted, based on the results of 33 separate injections, the topographic distribution of cortical projections throughout the amygdala. Areas TE and TEO of the inferotemporal cortex, portions of the superior temporal gyrus, and the granular region of the insula project primarily to the lateral nucleus, with little or no innervation of other amygdaloid nuclei. In contrast, orbitofrontal, medial prefrontal, and anterior cingulate regions project primarily to the basal and accessory basal nuclei and provide little innervation to the lateral nucleus. The orbitofrontal and medial prefrontal cortices, but not the anterior cingulate cortex, project to medially situated amygdaloid areas such as the cortical and medial nuclei and to the periamygdaloid cortex. The agranular and dysgranular insula, the parainsula, and rostral portions of the superior temporal gyrus project both to the lateral, basal, and accessory basal nuclei and to the medially situated nuclei. Projections to the central nucleus are particularly prominent from these regions. These data are discussed in relation to the hierarchical processing of sensory information that occurs within the amygdaloid complex.

The claustrum and the endopiriform nucleus contribute to the spread of epileptiform activity from the amygdala to other brain areas. Data of the distribution of pathways underlying the information flow between these regions are, however, incomplete and controversial. To investigate the projections from the amygdala to the claustrum and the endopiriform nucleus, we injected the anterograde tracer Phaseolus vulgaris leucoagglutinin into various divisions of the amygdaloid complex, including the lateral, basal, accessory basal, central, anterior cortical and posterior cortical nuclei, the periamygdaloid cortex, and the amygdalohippocampal area in the rat. Analysis of immunohistochemically processed sections reveal that the heaviest projections to the claustrum originate in the magnocellular division of the basal nucleus. The projection is moderate in density and mainly terminates in the dorsal aspect of the anterior part of the claustrum. Light projections from the parvicellular and intermediate divisions of the basal nucleus terminate in the same region, whereas light projections from the accessory basal nucleus and the lateral division of the amygdalohippocampal area innervate the caudal part of the claustrum. The most substantial projections from the amygdala to the endopiriform nucleus originate in the lateral division of the amygdalohippocampal area. These projections terminate in the central and caudal parts of the endopiriform nucleus. Lighter projections originate in the anterior and posterior cortical nuclei, the periamygdaloid cortex, the medial division of the amygdalohippocampal area, and the accessory basal nucleus. These data provide an anatomic basis for recent functional studies demonstrating that the claustrum and the endopiriform nucleus are strategically located to synchronize and spread epileptiform activity from the amygdala to the other brain regions. These topographically organized pathways also provide a route by means of which the claustrum and the endopiriform nucleus have access to inputs from the amygdaloid networks that process emotionally significant information.

We have used the anterograde tracer, Phaseolus vulgaris-leucoagglutinin (PHA-L) to study the intrinsic projections of the lateral nucleus of the Macaca fascicularis monkey amygdaloid complex. A reanalysis of the monkey lateral nucleus indicated that there are at least four distinct cytoarchitectonic divisions: dorsal, dorsal intermediate, ventral intermediate, and ventral. The major projections within the lateral nucleus originate in the dorsal, dorsal intermediate, and ventral intermediate divisions and terminate in the ventral division. The ventral division also projects to itself but does not project significantly to the other divisions of the lateral nucleus. Thus, the ventral division appears to be a site of convergence for information entering all other portions of the lateral nucleus. There are substantial regional and topographic differences in the projections from each of the lateral nucleus divisions to other amygdaloid nuclei. The dorsal division projects to all divisions of the basal and accessory basal nuclei, to the periamygdaloid cortex, the nucleus of the lateral olfactory tract, the dorsal division of the amygdalohippocampal area, and the lateral capsular nuclei. The dorsal intermediate division projects to the intermediate and parvicellular divisions of the basal nucleus, to the parvicellular division of the accessory basal nucleus, and to the periamygdaloid cortex. The ventral intermediate division projects to the magnocellular division of the accessory basal nucleus and to the parvicellular division of the basal nucleus. The major projections from the ventral division are directed to the parvicellular division of the basal nucleus, the parvicellular division of the accessory basal nucleus, the medial nucleus, and the periamygdaloid cortex. Projections from all portions of the lateral nucleus to the central nucleus are generally very light. It appears, therefore, that each division of the lateral nucleus originates topographically organized projections to the other amygdaloid areas that terminate in distinct portions of the target regions. The topographic organization of intrinsic amygdaloid projections raises the possibility that serial and parallel sensory processing may take place within the amygdaloid complex. J. Comp. Neurol. 398:431–458, 1998. © 1998 Wiley-Liss, Inc.

Information from most of the sensory modalities enters the amygdala via the lateral nucleus. The olfactory information, however, arrives at the amygdala through the superficial nuclei, including the periamygdaloid cortex. To find out whether the olfactory information can modulate the processing of sensory information in the lateral nucleus we injected Phaseolus vulgaris leucoagglutinin, an anterograde axonal tracer, into the different divisions of the periamygdaloid cortex. We found that the PAC division of the periamygdaloid cortex projects to the ventrolateral and medial divisions, but not the dorsolateral division, of the lateral amygdaloid nucleus. Therefore, the projection from the PAC to the lateral nucleus provides a route, by which the olfactory information may become associated with other sensory modalities. Also, together with our previous finding that the lateral nucleus projects to the periamygdaloid cortex, the present data demonstrate that the lateral nucleus and the PAC are reciprocally connected.

Previous studies have shown that the orbital and medial prefrontal cortex (OMPFC) is extensively connected with medial temporal and cingulate limbic structures. In this study, the organization of these projections was defined in relation to architectonic areas within the OMPFC. All of the limbic structures were substantially connected with the following posterior and medial orbital areas: the posteromedial, medial, intermediate, and lateral agranular insular areas (Iapm, Iam, Iai, and Ial, respectively) and areas 11m, 13a, 13b, 14c and 14r. In contrast, lateral orbital areas 12o, 12m, and 12l and medial wall areas 24a,b and 32 were primarily connected with the amygdala, the temporal pole, and the cingulate cortex. Data were not obtained on the posteroventral medial wall. Three distinct projections were recognized from the basal amygdaloid nucleus: 1) The dorsal part projected to area 12l; 2) the ventromedial part projected to most areas in the posterior and medial orbital cortex except for area Iai, 12o, 13a, and 14c; and 3) the ventrolateral part projected to orbital areas 12o, Iai, 13a, 14c, and to the medial wall areas. The accessory basal and lateral amygdaloid nuclei projected most strongly to areas in the posterior and medial orbital cortex. The medial, anterior cortical, and central amygdaloid nuclei and the periamygdaloid cortex were connected with the posterior orbital areas. The projection from the hippocampus originated from the rostral subiculum and terminated in the medial orbital areas. The same region was reciprocally connected with the anteromedial nucleus of the thalamus, which received input from the rostral subiculum. The parahippocampal cortical areas (including the temporal polar, entorhinal, perirhinal, and posterior parahippocampal cortices) were primarily connected with posterior and medial orbital areas, with some projections to the dorsal part of the medial wall. The rostral cingulate cortex sent fibers to the medial wall, to the medial orbital areas, and to lateral areas 12o, 12r, and Iai. The posterior cingulate gyrus, including the caudomedial lobule, was especially strongly connected with area 11m.

The amygdaloid complex plays an essential role in auditory fear conditioning of the Pavlovian type. The available evidence suggests that the lateral nucleus is the input station of the amygdala for auditory conditioned stimuli, whereas the central medial nucleus is the output for conditioned fear responses. However, the intrinsic pathway transmitting auditory information about the conditioned stimulus from the lateral to the central medial nuclei is unknown as there are no direct projections between these nuclei. The present study was undertaken to determine if the main intra-amygdaloid targets of the lateral nucleus, namely the basomedial and basolateral nuclei, project to the central medial nucleus. To this end, iontophoretic injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin were performed in these nuclei. To rule out the possibility that the anterograde labeling reflected passing fibers merging with the major fiber bundles that course in and around the central medial nucleus, labeled terminals and varicosities were observed in the electron microscope. It was determined that the basolateral and basomedial nuclei have partially overlapping intraamygdaloid targets. They both project to the central medial nucleus, nucleus of the lateral olfactory tract and peri-amygdaloid cortex, but have limited projections to each other. Small Phaseolus vulgaris-leucoagglutinin injections in both nuclei gave rise to prominent intranuclear projections but only the basomedial nucleus was found to project to the lateral and anterior cortical nuclei. At the electron microscopic level, all labeled axon terminals and varicosities formed asymmetric synapses (n = 245) with dendritic spines (83%) or with dendritic shafts (17%). This is the first unambiguous demonstration that the basolateral and basomedial nuclei project to the central medial nucleus. Since these nuclei constitute the main intra-amygdaloid targets of the lateral nucleus, they represent likely candidates for the transmission of auditory conditioned stimuli to the central medial nucleus in auditory fear conditioning.

We addressed the question whether the projection neurons of the olfactory bulb, i.e. the mitral and tufted cells, are immunoreactive for the calcium-binding protein, calretinin. The following approaches were adopted: (1) light and electron microscopic calretinin-immunocytochemistry; (2) neuroanatomical tracing combined with calretinin-immunocytochemistry according to double-peroxidase and double-fluorescence protocols; (3) unilateral lesion of the olfactory bulb combined with calretinin-immunocytochemistry. The experiments were carried out in rats. Immunostaining of brain sections revealed weakly calretinin-immunopositive mitral cell bodies. Tufted cells were immunonegative. In contrast, fibers in the lateral olfactory tract were strongly immunopositive. Dense immunostaining was also present in a superficial band in layer I of the olfactory tubercle, piriform cortex, periamygdaloid cortex, and in the lateral entorhinal cortex. In electron microscopic preparations of these target areas we observed immunoreaction product in axons and axon terminals. The latter invariably formed asymmetrical synapses, mostly with dendritic spines. Injections of the neuroanatomical tracer biotinylated dextran amine (BDA) into the olfactory bulb produced labeled fibers which remained completely restricted to the superficial, calretinin-immunopositive band in layer I in the above-mentioned cortical forebrain areas. We noted colocalization of transported BDA and calretinin-immunoreactivity in mitral cells, in fibers in the lateral olfactory tract and in fibers in the piriform cortex. Olfactory bulb lesions produced depletion of calretinin-immunoreactivity in the lateral olfactory tract and the superficial band in the olfactory cortex-related areas. Together these data firmly indicate that mitral cells and their axons are calretinin-immunoreactive.(ABSTRACT TRUNCATED AT 250 WORDS)

Calbindin-D28k is a calcium-binding protein located in a variety of neuronal cell types in many regions of the central nervous system. In the present study, we describe the distribution of calbindin-D28k-immunoreactive cells, fibers, and terminals in the monkey amygdaloid complex. Calbindin-D28k-immunoreactive neurons could be divided into four major cell types. Neurons of the first three cell types demonstrated clearly stained dendrites that were either aspiny or had a few spines on their distal portions. Type 1 cells were small, stellate, or multipolar and found throughout the amygdala. Type 2 cells were large, multipolar and were most commonly found in the deep nuclei, particularly in the lateral nucleus, intermediate division of the basal nucleus, accessory basal nucleus and in the periamygdaloid cortex. Type 3 cells were fusiform, of various sizes, and were found throughout the amygdala. Type 4 cells were quite large and lightly stained; the dendrites of these cells were usually unstained. The size, shape, and location of Type 4 labeled cell bodies suggested that they might be the large, modified pyramidal cells that constitute the projection neurons of the amygdala. Type 4 cells were observed primarily in the lateral, basal, and accessory basal nuclei and in the periamygdaloid cortex. Calbindin-D28k-immunoreactive fibers and terminals were difficult to observe in the amygdala partly because of a diffuse, finely granular neuropil labeling that was particularly dense in the anterior cortical and medial nuclei, in the central nucleus, and in the periamygdaloid cortex. The neuropil labeling was substantially lighter in the lateral, basal, and accessory basal nuclei. Conspicuous linear profiles resembling the “calbindin bundles” of the neocortex were evident in large numbers in the accessory basal nucleus, the medial portion of the parvicellular division of the basal nucleus, in the amygdalohippocampal area, and in the periamygdaloid cortex. There were calbindin-D28k-positive fibers in the stria terminalis and in the ventral amygdalofugal pathway. When the distributions of calbindin-D28k and parvalbumin immunoreactivity in the monkey amygdaloid complex were compared, it appeared that the overall distribution of these two calcium-binding proteins was generally complementary rather than overlapping. © 1993 Wiley-Liss, Inc.

Our earlier electrophysiological work provided evidence of a direct input to the supraoptic nucleus (SON) from the olfactory bulbs; however, these experiments could not determine if the input originated in the main and/or accessory portions of the olfactory bulb. Here, a connection between the accessory olfactory bulb (AOB) and the SON of the rat was examined using a combination of anatomic techniques. We employed neurophysin immunocytochemistry to delineate the morphological boundaries of the SON and the proximal arborizations of supraoptic dendrites. Accessory olfactory bulb efferents to the SON were studied by injection of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into the AOB. The distribution of retrogradely labeled cells within the AOB was also determined after injection of either rhodamine-labeled latex microspheres (rhodamine beads) or Fluoro-Gold (FG) into the SON. Neurophysin immunocytochemistry revealed that SON dendrites extended beyond the generally accepted boundaries of the nucleus, coursing ventrolaterally along the surface of the periamygdaloid cortex. Anterograde tract tracing with WGA-HRP labeled AOB efferents including a dense plexus of terminals and fibers around the ipsilateral SON along the path of the ventrally projecting dendrites. Injections of retrograde tracers into the SON resulted in rhodamine bead or FG labeling of mitral cells throughout the ipsilateral AOB. Taken together, these anatomic studies suggest a direct projection from the accessory olfactory bulb to the SON of the rat and thus a vomeronasal organ to SON pathway.

The ventral striatum is the part of the striatum associated with reward and goal-directed behaviors, which are mediated in part by inputs from the amygdala. The ventral striatum is divided into 'shell' and 'core' subterritories which have different connectional, histochemical and pharmacological properties. Behavioral studies also indicate that subterritories of the ventral striatum are differentially involved in specific goal-directed behaviors. The amygdala is a heterogeneous structure which has multiple nuclei involved in processing emotional information. While the existence of an amygdalostriatal pathway has long been established, the relationship between amygdaloid afferents and specific subterritories of the ventral striatum is not known. In this study we operationally defined the ventromedial striatum as the region receiving cortical inputs primarily from the orbital and medial prefrontal cortex. We placed retrograde tracer injections into subregions of the ventromedial striatum of macaques monkeys to determine the relative contribution of specific amygdaloid inputs to each region. Calbindin-D28k immunostaining was used to further define the shell subterritory of the ventromedial striatum. Based on these definitions, the amygdala innervates the entire ventromedial striatum, and has few to no inputs to the central striatum. The basal and accessory basal nuclei are the major source of input to the ventromedial striatum, innervating both the shell and ventromedial striatum outside the shell. However, a restricted portion of the dorsomedial shell receives few basal nucleus inputs. Afferent inputs from the basal nucleus subdivisions are arranged such that the parvicellular subdivision projects mainly to the ventral shell and core, and the magnocellular subdivision targets the ventral shell and ventromedial putamen. In contrast, the intermediate subdivision of the basal nucleus projects broadly across the ventromedial striatum avoiding only the dorsomedial shell. The shell has a specific set of connections derived from the medial part of the central nucleus and periamygdaloid cortex. Within the shell, the dorsomedial region is distinguished by additional inputs from the medial nucleus. The ventromedial caudate nucleus forms a unique transition zone with the shell, based on inputs from the periamygdaloid cortex. Together, these results indicate that subterritories of the ventromedial striatum are differentially modulated by amygdaloid nuclei which play roles in processing olfactory, visual/gustatory, multimodal sensory, and 'drive'-related stimuli.

The distribution of calbindin-D28k-immunoreactive cells and fibres in five human amygdalae was analysed from sections that had been stained immunohistochemically with a monoclonal antibody raised against calbindin-D28k. The highest density of calbindin-D28k-positive neurons were found in the anterior cortical, medial, posterior cortical and accessory basal nuclei, in the parvicellular division of the basal nucleus and in the amygdalohippocampal area. The lowest densities of immunopositive neurons were found in the paralaminar nucleus, in the periamygdaloid cortex (PAC1 and PACo) and in some of the intercalated nuclei. The deep nuclei (lateral, basal and accessory basal nuclei) contained a high density of calbindin-D28k-immunoreactive fibres and terminals. The cortical nuclei and the central nucleus were characterized by intense neuropil labelling. Morphologically, a large majority of the calbindin-D28k-immunoreactive neurons were aspiny or sparsely spiny and resembled inhibitory local circuit neurons. A small population of lightly-stained, pyramidal-shaped neurons was also observed. In most of the amygdaloid nuclei, calbindin-D28k-immunoreactive fibres travelled close to each other and formed bundles, which suggests that some of the immunostained neurons were double-bouquet cells. In the paralaminar nucleus, the calbindin-D28k-immunoreactive axons formed tortuous plexus (100–200 mm in diameter) that surrounded several unstained somata. This study provides baseline information on the morphology and distribution of calcium-binding protein-containing inhibitory cells and fibres immunoreactive for calbindin-D28k in the human amygdaloid complex. This information can be used in future studies on the pathogenesis of diseases known to damage the amygdala, such as Alzheimer's disease and temporal lobe epilepsy.

Retinal projections to the basal forebrain in male Syrian hamsters were examined at the ultrastructural level following bilateral intraocular injections of horseradish peroxidase conjugated to either cholera toxin (CT-HRP) or wheat germ agglutinin (WGA-HRP). Light level microscopic analysis confirmed retinal projections along basal telencephalon, and examination on the electron microscope of individual fibers from the peri-amygdaloid area revealed en passant synaptic profiles. Sections from animals treated with WGA-HRP showed evidence of transsynaptic communication in the form of labeled dendrites in the peri-amygdaloid area. Taken together, these data show that the retina communicates directly with the periamygdaloid area, where photic and chemosensory information may be integrated to modulate reproductive behavior.

Previous studies of the intrinsic connections of the amygdaloid complex in the rat, cat and monkey demonstrated that the lateral nucleus projects prominently to the accessory basal nucleus and periamygdaloid cortex and lightly to several other nuclei of the amygdala. Most previous studies have emphasized the lack of a connection between the lateral and basal nuclei. As part of ongoing studies of the intrinsic circuitry of the monkey amygdala, we have placed discrete, iontophoretic injections of the lectin anterograde tracer Phaseolus vulgaris leucoagglutinin into the lateral nucleus of the Macaca fascicularis monkey. In addition to confirming the well established intrinsic connections of the lateral nucleus, heavy fiber and terminal labeling was also observed in the adjacent basal nucleus. The projection innervated all divisions of the basal nucleus and tended to be somewhat denser rostral to the level of the injection site. This hitherto unreported intrinsic connection provides a means by which the lateral nucleus, which is the principal recipient of afferents from sensory neocortex, can influence cells of the basal nucleus, which originate the major amygdalofugal projection to the neocortex.

Using the autoradiographic tracing technique the retinal projections were studied in the tenrecs, Echinops telfairi and Setifer setosus (insectivora, tenrecidae). Bilateral projections were found to the n. suprachiasmaticus, the anterior hypothalamic area, the dorsal and ventral lateral geniculate bodies, the pretectal olivary nucleus and the superior colliculus. The contralateral projections were usually more intense than the ipsilateral ones except the retinohypothalamic connections. A partial segregation of the projection fields from both eyes was present in the dorsal and ventral lateral geniculate bodies. In the superior colliculus retinal fibers predominantly involved the stratum zonale and the upper portion of the stratum griseum superficiale on both sides. The projections to the deeper portion of the colliculi were rather faint, particularly on the ipsilateral side. Target areas receiving contralateral projections exclusively were the periamygdaloid area (labeled only in Setifer), the terminal accessory nuclei including the n. tractus optici and the inferior colliculus. The data are compared with other species. The most striking finding may concern the projection to the medial terminal nucleus being quite prominent in marsupials and most eutherian mammals (including the erinaceomorphous hedgehogs), but greatly reduced in tenrecs and primates.

The distribution of somatostatin-like immunoreactivity was studied in the macaque monkey (Macaca fascicularis) by using primary antisera that recognize somatostatin-28 (S309) or somatostatin-28(1-12) (S320). Somatostatin-immunoreactive neuronal cell bodies were observed in all amygdaloid nuclei and cortical regions. The density of labeled cells varied substantially, however, both within and across the various amygdaloid subdivisions. The highest densities of labeled neurons were observed in layer III of the periamygdaloid cortex, in layers II and III of the medial nucleus, in the magnocellular division of the accessory basal nucleus, and in the medial portion of the lateral nucleus. Many labeled cells were also consistently observed in the caudoventral portion of the lateral division of the central nucleus. Labeled cells were heterogeneous in size and shape ranging from small and spherical to large and multipolar. The density of somatostatin-immunoreactive fibers also varied greatly from region to region and was often inversely related to the density of immunoreactive cells. Highest densities of immunoreactive fibers were observed in the periamygdaloid cortex, medial nucleus, parvicellular division of the accessory basal nucleus, paralaminar nucleus, ventrolateral portion of the lateral nucleus, parvicellular division of the basal nucleus, and the lateral division of the central nucleus. Fibers and terminals in the central nucleus had a coarsely varicose appearance and this pattern of staining was continuous along the trajectory of the central nucleus projection to the bed nucleus of the stria terminalis. The large, immunoreactive varicosities located in this area often appeared to outline dendritic or vascular profiles within the substantia innominata. The lowest levels of somatostatin-immunoreactive fibers were observed in the magnocellular division of the basal nucleus and in the ventromedial portion of the accessory basal nucleus.

Injections of horseradish peroxidase were made into the basolateral nuclei of the amygdaloid complex in cats. It was shown that the periamygdaloid cortex immediately below the rhinal sulcus and extending medially to the amygdaloid fissure projects to the lateral nucleus. The rest of the periamygdaloid cortex medial to the amygdaloid fissure and including the cortical nucleus of the amygdala projects primarily to the basomedial nucleus. These cortico-amygdaloid projections originate in the deeper one-third of the cortex. No projections from the neocortex could be demonstrated.

The corticoamygdaloid and intraamygdaloid projections of the rat were studied by the use of retrograde transport of horseradish peroxidase (HRP). Observations based on anterograde transport of the enzyme were exploited to determine the course of the intrinsic connections. The HRP was injected stereotactically by means of iontophoresis. Most of the amygdaloid nuclei were selectively injected, and all but a few were reached by more than one approach. The vast majority of corticoamygdaloid fibers was found to originate in cortical areas defined as allocortical (Stephan, '75). From the medial frontal cortex the central amygdaloid nucleus (AC) receives a hitherto undescribed projection originating in the tenia tecta; and both the AC and the lateral amygdaloid nucleus (AL) receive fibers from the prelimbic and infralimbic areas. The anterior cingulate area entertains a weak connection with the basolateral amygdaloid nucleus (BL). As to the insular cortex, the posterior agranular insular area projects to all amygdaloid subdivisions; the BL, AC, and the anterior cortical nucleus (COa) receive, in addition, fibers from the ventral agranular area. The prepyriform cortex connects with the entire amygdala except the medial nucleus (Am). The amygdala receives afferents from a transitional area between the amygdala and the entorhinal area. The entorhinal area proper is related to the amygdala via projections from the ventral part of the lateral entorhinal area to the AL and from the dorsal part of the lateral entorhinal area to the BL. The former nucleus also receives fibers from the perirhinal region. Additional amygdalopetal connections from the hippocampal region include a previously undescribed projection from the temporal two-thirds of CA1 to the AL and BL and to the posterior cortical nucleus (COp) with the adjacent periamygdaloid cortex (PAC). The subiculum projections to the AL, and more modestly to other amygdaloid nuclei. There is an extensive network of intraamygdaloid connections, the Am and AC being the only nuclei not giving rise to the intrinsic fibers.

The interconnections between the amygdala and the hippocampal formation were investigated in the macaque monkey using anterograde tracers. The hippocampal inputs to the amygdala arose from the subicular and entorhinal cortices and passed through the angular bundle to terminate principally in the medial basal and lateral basal nuclei, with lighter termination in the lateral nucleus, the periamygdaloid cortex, and the cortical-transition area. The majority of these amygdaloid inputs arose from the rostral hippocampal formation although there was equivocal evidence of an additional projection from the caudal hippocampus to the central nucleus. Projections arose from many of the amygdaloid nuclei to terminate in the molecular layer of the amygdalo-hippocampal area and the adjacent stratum moleculare of the uncal portion of the hippocampus. The accessory basal, lateral basal, and medial basal nuclei also projected to the most rostral portions of the stratum moleculare of fields CA1-3, the heaviest termination occurring in field CA3. Additional projections from the basal nuclei terminated in the prosubiculum, presubiculum, and parasubiculum. The heaviest entorhinal inputs arose from the accessory basal and lateral nuclei and terminated in layers I, II, and III of areas 28b, 28i, and the prorhinal cortex. The major amygdaloid input to the perirhinal cortex arose from the lateral basal nucleus.

Projections are described from the basolateral, lateral and anterior cortical nuclei of the amygdaloid complex, and from the prepiriform cortex, to several discrete areas of the cerebral cortex in the rat and cat and to the mediodorsal thalamic nucleus in the rat. These projections are very well-defined in their origin, and in their area of laminar pattern of termination. The basolateral amygdaloid nucleus can be divided into anterior and posterior divisions, based on cytoarchitectonic and connectional distinctions. In both the rat and cat the posterior division projects to the prelimbic area (area 32) and the infralimbic area (area 25) on the medical surface of the hemisphere. The anterior division projects more lightly to these areas, but also sends fibers to the dorsal and posterior agranular insular areas and the perirhinal area on the lateral surface. Furthermore, in the cat the perirhinal area is divided into two areas (areas 35 and 36) and the anterior division projects to both of these and also to a ventral part of the granular insular area; this last area is adjacent to, but separate from the auditory insular area and the second cortical taste area. In most of these areas, the fibers from the basolateral nucleus terminate predominantly in two bands: one in the deep part of layer I and layer II, and a heavier band in layer V (in the rat) or layers V and VI (in the cat). The lateral amygdaloid nucleus projects heavily to the perirhinal area, and also to the posterior agranular insular area. These fibers terminate predominantly in the middle layers of the cortex, although the cellular lamination in these two areas is relatively indistinct. The anterior cortical amygdaloid nucleus and the prepiriform cortex both project to the infralimbic area and the ventral agranular insular area, and the anterior cortical nucleus also projects to the posterior agranular area and the perirhinal area. In all of these areas, the fibers from these olfactory-related structures terminate in the middle of layer I. In the rat, the two divisions of the basolateral nucleus also project to the medial segment of the mediodorsal thalamic nucleus, with the anterior division projecting mainly to the posterior part of this segment and the posterior division to the anterior part. The endopiriform nucleus, deep to the prepiriform cortex, projects to the central segment of the mediodorsal nucleus; this may constitute the major olfactory input into the mediodorsal nucleus, since little or no projection could be demonstrated from the prepiriform cortex itself. Projections to the mediodorsal nucleus have not been found in the cat.

The connections of the amygdala with the insular and temporal cortices were examined by injecting wheat germ agglutinin conjugated to HRP (WGA-HRP) into the rat cortex. Following injections into the posterior agranular insular area (AIp) or perirhinal cortex (PR), bands of labeled neurons extending across nuclear boundaries were observed in the amygdala. These neuronal bands involved cells in the lateral, basolateral, and basomedial nuclei as well as the periamygdaloid cortex. Other nuclei of the corticomedial amygdala and the ventral endopiriform nucleus also exhibited retrogradely labeled cells. Anterograde label was observed in nuclei containing labeled neurons and in the central nucleus. Injections into gustatory, somatosensory, and auditory neocortical areas located dorsal to AIp and PR labeled small numbers of cells in the lateral and basolateral nuclei. Injections into AIp, PR, and, to a lesser extent, dorsally adjacent neocortical areas produced both retrograde and anterograde labeling in the contralateral amygdala. The main nuclei with contralateral insular and temporal projections are the basomedial nucleus, ventral endopiriform nucleus, and nucleus of the lateral olfactory tract. The contralateral central nucleus and to a lesser extent the lateral nucleus exhibited anterograde labeling. The pattern of retrograde labeling seen with injections at different rostrocaudal levels of the AIp-PR continuum indicates that amygdalocortical projections to these areas exhibit an overlapping topographical organization. Comparison of the results of this study with findings on amygdaloprefrontal cortical efferents suggests that amygdaloid projections to the entire fronto-insulo-temporal mesocortical field are topographically organized.

Summary Through stimulation of the lateral amygdaloid nucleus (M of Volsch) we could produce remarkable changes upon respiratory movements, namely, diminution of amplitude and increase in the rate of respiration. The stimulation of the intermediate or medial nucleus of amygdala proper (T or T of Volsch, basal amygdaloid nucleus of Fox) may not bring about changes upon the respiratory movements; if effective, it is typified in the increase in the rate and amplitude of respiration, as it was previously recognized through stimulation of the periamygdaloid cortex. The motion of the diaphragm stands still at the moment of stimulation, regardless as to whether it stands in expiratory or in inspiratory position. The histological observation of the lungs revealed that changes such as hemorrhage, congestion, emphysematous and edematous change, were ext: aordinarily severe in the stimulated side, except in a few instances where much severe damage was shown in the contralateral side.

Summary Through bilateral destruction of the amygdaloid nuclear complex in infant and adult animals and through subsequent observations under careful feeding in sxne period of time, following results were obtained: 1) By bilateral amygdalectomy in infant animals, inhibition in the growth was induced in most cases. 2) Histological observations on the brain lesions of these cases reveal that the inhibitory effect upon the growth may be initiated seemingly by destruction of the medial amygdaloid complex such as nuclei B, D or T, or periamygdaloid cortex such as Pam2 and Pam3, or the anterior amygdaloid region, especially at the level of the nucleus of the lateral olfactory trac:. 3) The inhibitory effect upon the growth was exceedingly obvious in those cases, in which the amygdaloid regions or surrounding structures of these most effective parts of the amygdala were extensively damaged on both sides. 4) Somewhat accelerating effect upon the growth was found in some cases, however, no positive evidence could be gained by any means in this series of observation. 5) Unilateral arnygdalar or hypothalamic destruction cannot result in retardation of the growth, even in those highly convincing cases with tissie deterioration in the vicinity of the amygdala. 6) An example of remarkable obesity was found in an adult cat following bilateral destruction of the medial parts of the amygdala and a part of the entorhinal area. Histological alterations of the internal organs of this case were described and a functional relationship of the so-called feeding centre in the hypothalamus was discussed.

Summary The results of comparative-anatomical and experimental studies on amygdala disclosed the following facts: 1) The division of amygdaloid niiclei into two groups, basolateral and corticomedial seems to be not fully adequate in regard to the functional differences, because results of the stimulation experiments in our laboratory indicate for certain coincidence of effectiveness with autonomous function. From the view angle of fiber connection, this way of division ought also not to be highly evaluated. 2) The intermediate principal nucleus (nucleus T of Volsch large-celled lateral part of the basal nucleus of American authors) is generally divided into two parts, namely, dorsal and ventral portions. The ventral portion of that of the bat is particularly large and together with the large lateral principal nucleus nucleus M of Volsch, lateral nucleus of American authors) constitutes a characteristic of bat amygdala. The reason for its largeness was found, by means of destruction experiment of the amygdaln, in a close connection with the flight activity. Presumably intermediate prinripal nucleus participates in the extrapyramidal motor function; the lateral principal nucleus is generally large in most animals and functionally seems to inhibit motor activity. 3) The medial principal nucleus (nucleus T of Volsch, small-celled medial part of the basal nucleus of American authors) remains maldeveloped in some lower animals. In general, it grows distinctly larger in the caudal level. According to the result of the investigations undertaken in our laboratory, the said nucleus is chiefly related to autonomic nervous system. The above mentioned lateral and intermediate principal nuclei (T and T) also seem to have some relation, partially at least with autonomic nervous system. 4) The so-called medial nucleus in higher animals (D of Volsch) is generally maldeveloped. This nucleus, together with cortical nucleus (B of Volsch), participates partially also in autonomic nerve function. The central nuclei of higher animals (E and E of Volsch) are also underdeveloped 5) The periamygdaloid cortex (Pam1, Pam2 and Pam3 of Rose) receives the fibers from the lateral olfactory tract and evidently participates in olfactory function, but it also causes both extrapyramidal and autonomic reflexes probably by way of the amygdalar connection. Of the said cortical portions what are particularly closely related with amygdala are the portions Pam2 and Pam3. However, the portion Pam3 has not been differentiated yet in the lower animals. 6) When the bilateral amygdala of a young animal is destroyed early in life, growth gets markedly inhibited. In such an animal. atrophy of the parotid gland, thyroid gland, hypophysis, adrenal gland and pancreatic gland was observed. As the cause of this developmental disturbance there are two nervous routes assumable, namely, the route through amygdala hypothalamus anterior lobe of hypophysis general inner secretory glands and the route through amygdala salivary glands inner secretory disturbance of the latter. In the latter connection, the pituitary gland also may participate in the process. We should be particularly cautious about applying bilateral amygdalectomy to human subjects as there is a possibility of the occurrence of disturbances long after the operation. 7) That amygdala participates in salivation was verified by our experiments and the following facts also came to be clear as the result thereof: the portion Pam2 of periamygdaloid cortex has a particularly close connection with the secreting function of parasympathetic origin; of all the amygdaloid nuclei, the medial principal nucleus (T) has an especially close relation with saliva secretion of sympathetic origin, while the intermediate principal nucleus (T), cortical nucleus (B), medial nucleus (D) and hippocampus secret saliva of a parasympathetic origin. Unilateral stimulation produces secretion of bilateral salivary glands. The fibers starting from such portions seem to be led directly toward hypothalamus further to reach the lower part of the brain.

Characteristic bulbar potentials were evoked by retrograde stimulation of the lateral olfactory tract. Its projection was thereby traced into the prepiriform areas, the lateral part of the olfactory tubercle, the periamygdaloid area, cortical amygdaloid nucleus, anterior part of the medial nucleus, and throughout the parahippocampal area. This latter connection has not been described previously. By our definition the parahippocampal area lies immediately behind the periamygdaloid area and extends caudally alongside the posterior prepiriform area, being bounded caudomedially by the true entorhinal area which thus occupies only the most posterior part of the piriform lobe. Negative bulbar potentials were evoked when centrifugal systems were stimulated, crossed potentials being mediated by the anterior commissure. However, the commissure is not the only efferent pathway to the ipsilateral bulb. Centrifugal systems were demonstrated in relation to all regions receiving lateral olfactory tract afferents. Stimulation of these areas, both superficially and deeper in the cortex, evoked bulbar negativities even after interruption of the ipsilateral anterior limb of the anterior commissure, or section of the lateral olfactory tract in the peduncle. The close association of centripetal and centrifugal systems suggests that bulbar activity is under the influence of sensory feedback systems, as well as more central control.

The amygdaloid complex in the cat was studied in a series of Golgi preparations. Both the lateral and the basal nucleus are composed of the same two cell types, one of which (type P) resembles the pyramidal and the other (type S) the stellate neuron of the cortex. The cortical nucleus can be divided into three layers (I, II, and III–IV) which are made up of cells similar to those in the periamygdaloid cortex. In addition, there are sufficient differences in the organization of these layers to justify a subdivision of the cortical nucleus into lateral and medial parts. The dendrites of neurons in the medial part of the central nucleus, the medial nucleus and the anterior amygdaloid area undergo less branching and carry fewer spines than those of the type P cell. The neurons in the nucleus of the lateral olfactory tract are all of the pyramidal or modified pyramidal type. These findings are discussed in relation to those of previous investigators who employed the Nissl and Golgi methods.

Previous studies have shown that the amygdala projects to both the mediodorsal thalamic nucleus (MD) and its cortical projection area, the prefrontal cortex (PFC). In this investigation rats received injections of different fluorescent retrograde tracers (true blue and diamidino yellow) into MD and either the lateral, polar, or medial PFC in order to examine the relationship of amygdaloid neurons with cortical and/or thalamic projections. PFC injections labeled neurons in the basolateral (BL), basomedial (BM), ventral endopiriform (Env), and rostral lateral nuclei as well as the periamygdaloid cortex (PAC) and the medial part of the amygdalohippocampal area (AHA). In BL, which contained the great majority of neurons projecting to PFC, most labeled cells were concentrated in particular parts of the nucleus and were topographically organized. The overwhelming majority of labeled neurons in BL were large pyramidal or piriform cells that correspond to class I neurons described in Golgi studies. Occasional small neurons with thin dendrites were also observed; these cells may be class II neurons. MD injections labeled numerous cells in the anterior division of the cortical nucleus, medial nucleus, and caudomedial part of the central nucleus. Moderate numbers of labeled cells were found in caudal portions of BM and PAC, whereas scattered cells were observed throughout the rest of the amygdala with the exception of the lateral nucleus. In BL and AHA many MD-projecting neurons were observed along nuclear boundaries and in the adjacent white matter. Neurons in BL, BM, and AHA usually had large elongated or irregular somata and two to four primary dendrites that branched sparingly. Other cells had smaller ovoid somata. The morphology and distribution of MD-projection cells in the basolateral amygdala indicate that they are primarily large class II neurons. Double-labeled amygdaloid neurons, labeled by both cortical and thalamic injections, were observed only in a small number of animals. Control experiments suggest that most of the double-labeled cells in these cases were artifacts caused by spread of the thalamic injectate into the third ventricle with subsequent uptake by fibers in the anterior commissure. Thus the findings of this study suggest that different neuronal populations in the amygdala project to the two poles of the MD-PFC system. In the basolateral amygdala class I neurons are the predominant cell type involved in PFC projections, whereas a subpopulation of class II neurons, hitherto thought to be primarily local-circuit neurons, project to MD.

The projections of the hypothalamus to the amygdala have been studied autoradiographically in a series of eleven cynomolgus monkeys (Macaca fascicularis) in which injections of [3H]amino acids had been made in different regions of the caudal two-thirds of the hypothalamus. The most prominent projection arises from the ventromedial nucleus of the hypothalamus and terminates most heavily in the medial, magnocellular division of the central nucleus. Injections confined to the ventromedial nucleus also result in labeling of the piriform cortex, the periamygdaloid cortex, the anterior amygdaloid area, the medial amygdaloid nucleus and the parvocellular divisions of both the basal and basal accessory nuclei. All these projections are bilateral (although the contralateral component is much smaller) and show evidence of a rostro-caudal topographic organization. Isotope injections that involve the caudal part of the lateral hypothalamic area label projections to the medial division of the central amygdaloid nucleus, to the medial and cortical nuclei and to the anterior amygdaloid area. When such caudally placed injections also involved the lateral mamillary nucleus, the lateral division of the central amygdaloid nucleus was additionally labeled. Although the medial mamillary nucleus does not project to the amygdala, there is evidence for a minor projection from the supramamillary region to the medial amygdaloid nucleus. The ventral tegmental area appears to project to the lateral division of the central nucleus and the medial portion of the substantia nigra has a small projection to both divisions of the central nucleus. All of these projections reach the amygdala by way of the so-called ventral amygdalofugal pathway, but at least some of the fibers that arise in the ventromedial nucleus run in the stria terminalis.

The temporal neocortical afferent connections to the amygdala were investigated in the rhesus monkey using the silver impregnation and autoradiographic tracing methods. A large topographically organized projection to the amygdala was found to originate from the anterior superior temporal gyrus (area TA), the anterior middle and inferior temporal gyri (area TE), and the medial and lateral aspects of the temporal pole (area TG). These projections terminate in discrete adjacent regions of the lateral and basal amygdaloid nuclei. The temporal pole projection terminates in the ventral two thirds of the medial one half of the lateral nucleus and in the accessory basal nucleus, the anterior superior temporal gyrus projection terminates in the ventral two thirds of the lateral one half of the lateral nucleus, and the anterior middle and inferior temporal gyri projection terminates in the dorsal parts of the lateral and lateral basal nuclei. A projection from the perirhinal cortex to the medial basal nucleus of the amygdala is also discussed. Our findings reveal that a far greater proportion of the temporal neocortex than previously described contributes afferents to the amygdala, further strengthening the view that the amygdala occupies a key anatomical position linking the neocortex with diencephalic structures.

The intrinsic amygdaloid connections of the cynomolgus monkey were investigated using the autoradiographic method. Additional evidence concerning the origin of some intra-amygdaloid connections was provided by a series of rhesus monkeys with injections of horseradish peroxidase (HRP) in the amygdaloid complex. The experiments indicated that each of the major amygdaloid nuclei possesses a unique, organized set of intrinsic projections. Furthermore, there were large differences in the magnitude of the internal connections arising from or terminating in the various nuclei. The heaviest intrinsic projections arose from the lateral and basal nuclei while the central, medial, cortical, and accessory basal nuclei received the greatest number of these afferents. Thus, there was a clear trend for the bulk of these connections to run dorsally and medially within the amygdala. One important function of these intrinsic connections may be the integration of afferent sensory information from the various association areas which project to the amygdala.

The afferent projections to the primate amygdala were studied using horseradish peroxidase. The potential advantages of this technique are discussed compared with those previously used to determine amygdaloid afferents. The findings indicate that certain agranular or dysgranular cortical regions may project directly to the amygdala: in particular, the orbital frontal cortex, anterior cingulate gyrus, subcallosal gyrus, temporal pole and anterior insula. These projections probably terminate predominantly in either the lateral or accessory basal nuclei. Other cortical projections from the inferotemporal and superior temporal gyri are described. Evidence was found for a heavy projection from the superior temporal sulcus to the lateral nucleus. Subcortical afferents were found from the hypothalamus, substantia innominata, diagonal band, thalamus, periaqueductal central gray, peripeduncular nucleus and from a band of cells extending medially from the peripeduncular nucleus to the midline, just ventral to the thalamus. In the thalamus, labelled cells were restricted to the non-specific nuclei, and were common in the rostral midline nuclei. No projection was observed from the dorsomedial nucleus of the thalamus. We discuss the implications of these results for interpreting the functions of the amygdala.

The cytoarchitectonic structure and divisions of the amygdaloid complex are described in the rat and cat, with special reference to the axonal connections of each of the amygdaloid nuclei, and to interspecies variations and similarities. Several intra-amygdaloid connections are also described, based on autoradiographic experiments with small injections of 3H-amino acids into the individual nuclei. Although it has probably not been possible to determine all of the intra-amygdaloid projections from these experiments, the connections which have been shown are very specific. The lateral nucleus projects to the basomedial nucleus, the lateral part of the central nucleus, and the periamygdaloid cortex, while the basolateral nucleus projects only to itself, the medial part of the central nucleus, and the nucleus of the lateral olfactory tract. The basomedial nucleus projects to the cellular layer of the medial nucleus and the amygdalo-hippocampal area, while the molecular layer of these structures and of the posterior cortical nucleus, receives projections from the periamygdaloid cortex or from the endopiriform cortex. There are also interconnections between the medial and posterior cortical nuclei, and commissural connections between the posterior cortical nuclei of the two sides.

The organization of the cholinergic innervation of the macaque monkey amygdaloid complex was investigated by means of immunohistochemical techniques and either a polyclonal antiserum or a monoclonal antibody directed against the specific synthetic enzyme choline acetyltransferase (ChAT). Adjacent series of sections were processed histochemically for the demonstration of the degradative enzyme acetylcholinesterase (AChE) or for cell bodies with thionin. The density of ChAT immunoreactivity differed substantially among the various nuclei and cortical regions of the amygdala. In general, the distribution of ChAT immunoreactivity paralleled the pattern of AChE staining. One notable exception was the presence of AChE containing cell bodies in addition to AChE positive fibers within nearly all of the nuclear and cortical regions. In contrast, ChAT immunoreactivity was associated only with fibers and terminals. The highest density of ChAT immunoreactive fibers and terminals was consistently observed in the magnocellular subdivision of the basal nucleus. Staining was substantially less dense in the more ventrally situated parvicellular subdivision. Medially, in the adjacent accessory basal nucleus, immunoreactive fibers and terminals were densest in the magnocellular and superficial subdivisions and least prominent in the parvicellular subdivision. Of the deep nuclei, the lateral nucleus generally contained the least ChAT immunoreactive terminals and processes. Only its more densely cellular ventrolateral portion contained appreciable fiber and terminal staining. One of the more distinctive patterns of ChAT immunoreactivity was seen in the nucleus of the lateral olfactory tract. Here, ChAT positive fibers formed pericellular basket plexuses around unstained cell bodies. This unique pattern of staining was used to delineate the boundaries of the nucleus and indicated that it is present for much of the rostrocaudal extent of the amygdala. Another region of conspicuous staining on the medial surface of the amygdala was the sulcal portion of the periamygdaloid cortex. This region, associated with the sulcus semiannularis and bordering the entorhinal cortex, consistently contained dense immunoreactivity. The central nucleus also presented a somewhat idiosyncratic pattern of ChAT staining. The lateral subdivision had a diffuse distribution of immunoreactivity in which focal patches of more densely stained terminals and occasional fine fibers were embedded. In contrast, the medial subdivision contained a larger number of thicker, stained fibers without diffuse background labeling. Of the remaining amygdaloid nuclei, the amygdalohippocampal area contained dense ChAT staining, whereas progressively lighter staining was seen in anterior amygdaloid, posterior cortical, anterior cortical, and medial nuclei.

Summary Surface potentials were recorded in olfactory cortex of the guinea pig in vitro following stimulation of the lateral olfactory tract. In agreement with other investigators, stimulation of slices incubated at 37 °C evoked a surface negative wave in prepyriform cortex, olfactory tubercle and periamygdaloid cortex, but the surface-positive wave seen in vivo was absent. Variations in slice thickness indicated that the surface-negative wave was generated superficially since it could be evoked in slices as thin as 0.28 mm and that the surface-positive wave was generated from deeper layers since it could not be seen in slices less than 0.46 mm thick. To provide adequate oxygenation, the thicker slices were incubated at ambient temperatures. At these temperatures, 0.46–0.78 mm thick slices exhibited surface negative waves over the entire olfactory cortex, including entorthinal cortex, as well as sequential surface-negative and surface-positive waves over the periamygdaloid cortex. Optimum conditions were obtained with slices 0.52 mm thick, incubated in Krebs solution containing2.5m M Ca 2+ at 23–27 °C. Under these conditions evoked potentials were well maintained up to 1–2 days. Such slices demonstrated intracellular Na + , K + and water contents similar to those of thinner slices incubated at 37 °C. The surface positivity was sensitive to changes in calcium, magnesium and stimulus-frequency in a manner suggesting a synaptic potential.

Publisher Summary The primate frontal lobe can be divided into three major parts: (1) the medial, defined by its projections from the anterior nuclear group; (2) the dorsolateral, defined by its projections from the microcellular portion of the medial thalamic nucleus; and (3) the posterior orbital, deriving projections from the midline of the thalamus and so heavily connected to the adjacent anterior insula, temporal pole, and periamygdaloid cortex. This chapter illustrates a model of inhibitory interactions that took place within the afferent channels. Collateral and recurrent afferent inhibitions were bucked against one another, forming a primary couplet of neural inhibition within afferent channels. Four forebrain mechanisms were assumed to provide efferent control on the primary couplet. Two of those—frontotemporal and sensory specific-intrinsic—influenced the couplet by regulating collateral inhibition whereas two others—hippocampal and polysensory motor—regulated recurrent inhibition. The frontal cortex appeared critically involved in implementing executive programs when those were necessary to maintain brain organization in the face of insufficient redundancy in input processing and in the outcomes of behavior.

Summary The amygdaloid complex of Ungulata is not so well developed in comparison with that of Carnivora, but a more or less high degree of differentiation than in Rodents, especially in the nucleus T, which likely comes out from the cortical element during the early embryonal period. Cells of this nucleus have a tendency in the adult to get segregated in small glomerulus-like groups, especially prominent in the cow. Another nuclei T' and M of amygdala proper are also well developed. But the central and medial nuclei E and D appear rather underdeveloped in comparison with those of Rodents. Although the small-celled nucleus K is generally well developed and separated in numerous groups, the correspondent to the nucleus intercalatus of Rodents can not be detected in Ungulata. The degree of differentiation of periamygdaloid cortex is rather advanced as it is divisible here into 3 parts, PA1, PAi and Pam, very likely corresponding to Pam1, Pam2 and Pam3 of Rose respectively. The nucleus B is here completely separated from the cortex Pam PAi of the horse is complicated in its cellular architecture as it is divisible into two subdivisions. In the cow the whole extept of periamygdaloid cortex is complicated as in the nucleus T, both showing glomerulus-like cell-islets. If these complicated features speak for the advanced degree of differentiation of this region with its functional significance parallel going, then the cow or bull might be most developed among the animals concerned, then follow the goat, horse and pig in developmental order downwards. In accordance with the classification in taxology in Ruminantia (cow and goat) and Non-Ruminantia (pig) of Archiodactyla and in Perissodactyla (horse), the cytoarchitectural patterns are each characteristic in these three groups. As to the fiber connection of the amygdaloid complex, the author has treated several fiber bundles of relatively well recognizable make-up. Their exact origin and termination have however to be determined by experimental investigation later on. In fact there must be numerous and complicated fibers hitherto untouched by the authors. Indication lies here in this study of Ungulata as it introduced several fiber bundles hitherto unkndwn, seemingly favored by larger form of brains studied. Concerning the islet-like groups of cells in the cow and goat, the author could not detect any specific fibrous characters even through application of certain axon-staining method, except that of compactly arranged capsule-like fibers. The assumption that the amygdala stands so intimately in relation with the cerebral cortex as the thalamus, or that it represents a vegetative centre or that it belongs to the extrapyramidal system, seems to be far from being entirely groundless as far as it concerns with the above mentioned anatomical investigation, but the lack of verification in experimental way leaves things to be entrusted to future researches.

Publisher Summary The central part of the mammalian olfactory system is made up by the olfactory bulb and those areas in the central nervous system that receive secondary olfactory fibers from the olfactory bulb. These structures are situated in the basal part of the telencephalon and show in the wide range of mammals, from macrosmatic opossum to microsmatic man, considerable variations in size and position. This chapter focuses on the cytoarchitectonics and fiber connections of the bulbar and retrobulbar areas. As to the structure of the other parts of the olfactory lobe, it is relevant to note that the cortical areas that receive secondary olfactory fibers—the prepyriform and periamygdaloid cortex and olfactory tubercle consist of three layers: (1) the plexiform or molecular layer, of which the superficial part is occupied by the fibers and collaterals of the lateral olfactory tract; (2) the pyramidal cell layer, consisting of small and medium-sized pyramidal cells; and (3) the polymorph cell layer, which contains fewer neurons than the preceding layer.

Summary A series of experiments was performed in an attempt to establish the anatomical localization of the effects upon uterine movements and ovulation due to the stimulation of the amygdaloid complex. A remarkable change in the uterine movements was recognized through electrical or chemical stimulation of delimitd parts of the amygdaloid nuclei in dogs, cats and rabbits. In pxtpartum and in non-pregnant matured animals, as well as in the latter half of pregnancy, an increase of tonus in uterine musculature and auginentation in frequency and amplitude of uterine motility can be evoked through unilateral stimulation of the medial principal amygdaloid nucleus (T of Volsch). These effects vary more or less according to the animal species and rather greatly by the stadium of sexual cycle at the time of experimentation. Stimulation of the lateral principal nucleus (M of VoZsch), the intermediate principal nucleus (T' of Vosch), the so-called cortical amygdaloid nucleus (B of Vosch), the medial amygdaloid nucleus (D of Vosch) and the central amygdaloid nucleus (E of Vosch) seems to be altogether ineffective. Stimulation of the periamygdaloid cortex gives an equally hardly effect upon the uterine motility. The impulse from the amygdala passes very likely through fibers corresponding to MV or MD fiber described by Fukuchi in Ungulata or through so-called medial forebrain bundle and is led to the viscero effective centre of the hypothalamus. The electrical stimulation of nuclei T and T' of the amygdala is capable of producing ovulation or hemorrhagic follicle in the ovary of the matured estrous rabbit. The impulse seems to go from the amygdala directly to the ventro medial nucleus of the hypothalamus leading further to the anterior pituitary lobe. The further effect to the ovary may be governed by the gonado tropic hormone released from the anterior pituitary lobe. In this latter case the estrous phase of the animals may also play an important role. (This work was aided in part by a grant from the Science Research Foundation of the Educational Department.

Summary 1) Through stimulation of the medial principal nucleus of amygdala proper (T of Volsch), most remarkable pupillary dilatation was called forth generally in both sides and in response to unilateral stimulation. Exophthalmus, abduction of eyeballs, retraction of the nictitating membranes, and nystagmus of small amplitude were also manifested. 2) Through stimulation of the lateral principal nucleus of amygdala proper (M of Volsch), there appeared in the most cases a slight degree of mydriasis. The movement of the nictitating membranes and nystagmus were also observed. 3) The stimulation of the intermediate principal nucleus of amygdala proper (T of Volsch prepared a causative also to the same phenomena, but owing to lesions in the neighboring nuclei, the results remained far from being eviding. Still, a small anterior part of nucleus T' seemed to stand in connection with pupillary constriction. 4) Functional bearing of the periamygdaloid cortex upon the pupillary dilatation was to be said quite weak, likely concerned with periamygdaloid area Pam2 of Rose. Unlike tremor of the eyelids which came out most remarkably and more frequently, nystagmus appeared upon periamygdaloid stimulation only in three cases out of 10 experiments and was of large amplitude, its quick component directed toward the operated side and making a good contrast to the excitatory case observable in cases of the nucleus T stimulation. The movement of eyes was not exactly recognizable. The nictitating membranes were protruded in about half of the cases, presumably to be concerned with fuxction of Pam1 of Rose. 5) Stimulation of Walker's ares 13 aroused a moderate till remarkable pupillary dilatation. The neuronal relationship of this area was to consider as definitely different from that of amygdala. It should be added that Brodmann's area 53 showed also dilatatory effect 6) Removal of the cervical sympathetic ganglion worked toward diminution of the dilatatory effect of amygdala. 8) The neuronal relationship of the dilatatory effect of amygdala was attacked through series of sectioning experiments and resulted in proving that the fiber path passed through the fibers correspondent to the M. V. and M. D. of Fukuchi in Ungulata.

The fields of origin of the amygdalofugal pathways in the albino rat were studied by using the Fink-Heimer technique to stain degenerating fibers and terminals in brains of animals sacrificed four and seven days after small unilateral lesions of the amygdale. A surprisingly restricted field of origin was found for the supracommissural stria terminalis — the component projecting to the ventromedial nucleus of the hypothalamus Only a lesion in the most posterior part of the cortical nucleus produced degeneration in this pathway. The postcommissural stria terminalis which apparently distributes to the bed nucleus of the stria terminalis and preoptic area originates in a more widespread area including parts of both the basolateral and corticomedial complexes. Although intense terminal degeneration could be seen within the amygdala following all lesions, long fibers projecting into the anterior amygdaloid area, lateral preoptic area and lateral hypothalamus were found only after lesions in which fibers of passage from periamygdaloid cortex could have been interrupted. Convincing evidence, therefore, of a long axon ventral amygdalofugal pathway of the rat was not found in this study.

Summary We can produce movements of ears and eyelids Iiy stimulation of the anterior part of the cortex of the pyriform lobe. In their neuronal relationship it is different from those evoked from the lateral surface of the hemisphere or from the masticatory movement made excitible from the pyriform lobe. The impulse may apparently be transmitted from that part of the cortex directly, yerhnps through the medial parts T and T (Volsch) of the amygdaloid nuclei leading into the subrortical gray matters; thereby cortical face-area and thalamus seem to play no part in it. Exact histological investigation concerning the effective area was done by the melhod of Marchi and Nissl. From these experiments it is likely that we may ascertain that the amygdaloid and periamygdaloid areas are concerned with the extrapyramidal motor system in certain respects.

After lesions of the olfactory bulb, coarse degenerating fibers were traced by the method of Nauta and Gygax through the lateral olfactory tract to superficial terminations in the prepiriform and periamygdaloid cortex and olfactory tubercle. Fine degenerated fibers were traced from the bulb through the anterior limb of the anterior commissure to terminations among the less superficial cells of the prepiriform cortex and olfactory tubercle. No fibers from the bulb reached the hippocampus or entorhinal area in these three species. After lesions in the olfactory tubercle, prepiriform cortex, or preoptic area, however, degenerated fibers were traced to the entorhinal area, subiculum, and hippocampus. There were some species differences in the distribution of these fibers, but a clear anatomical basis was found for the relay of olfactory impulses to the hippocampus. Rabbit and rat brains with lesions affecting the medial forebrain bundle at various levels were examined. Degenerated fibers were found to ascend through the bundle to the septum and fornix, and to be distributed from the fimbria throughout the extent of the ipsilateral hippocampus, passing right down to the ventral pole.

Summary The stimulation on cats amygdala, either electrical or chemical, sometimes causes cessation of movements both of the stomach and small intestine and the lowering of tension therein, though there are also cases with negative effect. In case of marked change it deals with stimulation chiefly on the medial principal nucleus (nucleus T of Volsch); in case of no change, with stimulation chiefly on the other subnuclei. No change took place in the small intestine when stimulation partook the periamygdaloid cortex exclusively. Judged from the resubs of both severing and destruction experiments, the fibers instrumental for such change concerning gastro-intestinal motility of amygdalar origir, are assumed directly to run downward through the ipsilateral hypothalamus Trigonum olfactorium, area 13, hippocampus, fornix, stria terminalis and capsula externa do not participate in the course There are a large number of pressor pints in periamygdaloid cortex (PA) and the most marked focus thereof is situated in Pam2. Both the electrical and chemical stimulation on amygdala proper (A) causes the same blood pressure elevation as that on PA. However, the effect of chemical stimulation is generally less marked than that of the electrical one. Among the subnuclei of “ A”, that is laden with the most marked pressure acceleration, is the nucleus T, next come nuclei M, T‘, B and D. It is quite likely that the neumn pnjected from “ PA ” gets renewed at “ A” With regard to the blood pressure there seems to exist no connection between area 13 and “A” nor trigonum olfactorium and “ A.” Also, fiber connection by the way of the posterior and medial part of piriform lobe must be denied. Althongh both sides of amygdala stand in a close connection with each other, the commissural and association fibers running in these do not seem to go propagating the function at least so far-as blood pressure is concerned. The result of stimulation, especially following dissection of stria terminalis, speaks for that the pressure effect brought about by either “PA” or “A” stimulation goes propagating by the way of the said fibers Judging from the result of the simultaneous observation of respiratory movement and blood pressure, the two seem to go propagating by the way of different fibers as they react in evidently different ways. In the case of stimulation experiment performed with the destruction of hypothalamus aforegoing, there was no stimulation effect displayed ipsilateral to the destruction. Presumably, the blood pressure change reaches hypothalamus of the stimulated side by the way of the ipsilateral stria terminalis to be transmitted therefrom to the lower center.

Publisher Summary This chapter discusses the connections of the olfactory bulb and the anterior olfactory nucleus in some mammals. In 13 young and 18 adult guinea pigs surgical and electrolytic lesions are made in the bulbus olfactorius and the nucleus olfactorius anterior. The lateral olfactory tract forms the only projection bundle of the olfactory bulb and accessory olfactory bulb. Fibers from this tract terminate in the pars externa and pars lateralis of the anterior olfactory nucleus, prepiriform cortex, lateral part of the olfactory tubercle, anterior amygdaloid area, nucleus of the lateral olfactory tract, and periamygdaloid cortex. The area of distribution of the lateral olfactory tract in the amygdaloid complex is limited to the antero-lateral part of the cortical nucleus. The lateral olfactory tract plausibly receives fibers from the pars lateralis of the anterior olfactory nucleus. The pars rostralis of the anterior olfactory nucleus projects via the anterior limb of the anterior commissure to the pars externa of the heterolateral anterior nucleus. The pars dorsalis of this nucleus projects to the heterolateral main and accessory olfactory bulbs. The pars medialis of the anterior olfactory nucleus contributes its fibers principally, if not exclusively, to the medial forebrain bundle.