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Contrast-enhanced cerebral blood volume-weighted (CBVw) fMRI response peaks are specific to the layer of evoked synaptic activity (Poplawsky et al., 2015), but the spatial resolution limit of CBVw fMRI is unknown. In this study, we measured the laminar spread of the CBVw fMRI evoked response in the external plexiform layer (EPL, 265 ± 65 μm anatomical thickness, mean ± SD, n = 30 locations from 5 rats) of the rat olfactory bulb during electrical stimulation of the lateral olfactory tract and examined its potential vascular source. First, we obtained the evoked CBVw fMRI responses with a 55 × 55 μm(2) in-plane resolution and a 500-μm thickness at 9.4 T, and found that the fMRI signal peaked predominantly in the inner half of EPL (136 ± 54 μm anatomical thickness). The mean full-width at half-maximum of these fMRI peaks was 347 ± 102 μm and the functional spread was approximately 100 or 200 μm when the effects of the laminar thicknesses of EPL or inner EPL were removed, respectively. Second, we visualized the vascular architecture of EPL from a different rat using a Clear Lipid-exchanged Anatomically Rigid Imaging/immunostaining-compatible Tissue hYdrogel (CLARITY)-based tissue preparation method and confocal microscopy. Microvascular segments with an outer diameter of

Both the lateral olfactory tract (LOT) and anterior limb of the anterior commissure (AC) carry olfactory information. The LOT forms the projection from the olfactory bulb to the ipsilateral olfactory cortices, while the AC carries odor information across the midline to the contralateral olfactory cortex and bulb. The LOT and AC differ on a number of dimensions, including early development and functional onset. The present work, examining their myelination in mice, reveals additional important differences. For example, the LOT initiates myelination 3–4 days earlier than the AC, evidenced by both an earlier increase in myelin basic protein staining seen with immunohistochemistry and an earlier appearance of myelinated fibers using electron microscopy. While both exhibit a period of rapid myelination, it occurs 4–5 days earlier in the LOT than the AC. The tracts also respond differently to early sensory restriction. Unilateral naris occlusion from the day after birth to postnatal day 30 had no consistent effects on the AC, but resulted in significantly thinner myelin sheaths relative to axon caliber in the LOT. Finally, the two tracts differ structurally (the LOT contains larger, more densely packed axons with significantly thicker myelin sheaths resulting in a conduction velocity that is more than twice as fast as the AC). The findings indicate that these two large, accessible tracts provide an important means for studying brain maturation due to basic differences in both the timing of their maturation and general organization.

It is well known that acetyl-L-carnitine (ALC) has various neuroprotective effects against neurodegenerative diseases. In addition, it has been reported that ALC facilitates myelination of regenerated axons after peripheral nerve injuries. We previously reported that spontaneous regeneration of the lateral olfactory tract (LOT), the main fiber tract of the central olfactory system, consistently occurred in newborn rats and a majority of these regenerated fibers were unmyelinated in neonatally LOT-transected young adult rats. To investigate the effects of ALC treatment on myelination in LOT, neonatal rats were treated with ALC after LOT transection. Immunohistochemistry for myelin basic protein showed more positive areas in ALC-treated rats than in control rats. Moreover, the number of myelinated axons of regenerated fibers was assessed using electron microscopy and was found to be statistically higher in ALC-treated rats compared to control rats. The study revealed that ALC accelerates myelination of regenerated fibers in neonatally LOT-injured young adult rats. (C) 2017 Elsevier B.V. All rights reserved., Article, NEUROSCIENCE LETTERS.653:215-219(2017)

It was revealed that regeneration of the lateral olfactory tract (LOT) occurred in developing rats and the regenerated olfactory system was functional 4 weeks after transection. The aim of this study was to determine the earliest onset of functional recovery in LOT-injured rats and to quantify regenerated nerve components with functional correlation. Neonatal rats on postnatal day (P) 2 were subjected to unilateral transection of the left LOT and underwent unilateral removal of the right olfactory bulb on P11. Functional recovery of the tract injury was assessed by the suckling capability, which can be achieved by olfaction. Suckling capability was observed on P12 in most neonatally LOT-transected pups. Rat pups were subjected to unilateral transection of the left LOT on P2, and received injections of biotinylated dextran amine (BDA) into the bilateral olfactory bulb on P5 to quantify normal and regenerated nerve components in the olfactory cortices at the level of the olfactory tubercle. BDA(+) areas and density indices of the olfactory cortices in the neonatally LOT-transected P12 pups were 11.05 × 10 5 μm 2 and 0.35 on the normal right side and 4.34 × 10 5 μm 2 and 0.21 on the transected left side. We concluded that functional recovery of the LOT-transected neonatal rats occurred as early as 10 days after tract transection and that areas and densities of regenerated nerve components essential for functional recovery were approximately 40% and 60% of the age-matched normal values in the olfactory cortices at the level of the olfactory tubercle.

信州大学博士（医学）・学位論文・平成24年3月31日授与（甲第915号）・関口泰之, The lateral olfactory tract (LOT) is a central olfactory pathway, and efferent projections from the olfactory bulb are conveyed to the olfactory-related cortical structures via the LOT. The purpose of the present study is to determine the exact site of the LOT causing functional impairment in animals. After ablation of the right olfactory bulb, rats received rostrocaudal transection injuries on the left LOT at different levels between the olfactory bulb and the middle cerebral artery. Olfactory function of LOT-transected rats was studied by examining their olfactory ability to discriminate between the smell of water and cycloheximide solution, a strong repellent for rodents. Rats were divided into two groups based on their olfactory discriminative abilities. The olfaction positive (+) group achieved 83% +/- 1% correct responses and the distances of the LOT-transected sites from the middle cerebral artery of this group ranged between 0.8 and 2.4 mm (n = 8). The olfaction negative (-) group achieved 48% +/- 1% correct responses and the distances of the LOT-transected sites from the middle cerebral artery ranged between 2.5 and 4.2 mm (n = 10). From these data, we concluded that the site of the LOT critical for olfactory function is located approximately 2.5 mm from the middle cerebral artery. (c) 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved., Article, NEUROSCIENCE RESEARCH. 73(1):17-23 (2012)

The Actinopterygii or ray-finned fishes comprise, in addition to the large superorder of teleosts, four other superorders, namely the cladistians, the chondrosteans, the ginglymodes, and the halecomorphs, each with a limited number of species. The telencephalon of actinopterygian fishes differs from that in all other vertebrates in that it consists of a pair of solid lobes. Lateral ventricles surrounded by nervous tissue are entirely lacking. At the end of the nineteenth century, the theory was advanced that the unusual configuration of the forebrain in actinopterygians results from an outward bending or eversion of its lateral walls. This theory was accepted by some authors, rejected or neglected by others, and modified by some other authors. The present paper is based on the data derived from the literature, complemented by new observations on a large collection of histological material comprising specimens of all five actinopterygian superorders. The paper consists of three parts. In the first, a survey of the development of the telencephalon in actinopterygian fishes is presented. The data collected show clearly that an outward bending or eversion of the pallial parts of the solid hemispheres is the principal morphogenetic event in all five actinopterygian superorders. In all of these superorders, except for the cladistians, eversion is coupled with a marked thickening of the pallial walls. In the second part, some aspects of the general morphology of the telencephalon in mature actinopterygians are highlighted. It is pointed out that (1) the degree of eversion varies considerably among the various actinopterygian groups; (2) eversion leads to the transformation of the telencephalic roof plate into a wide membrane or tela choroidea, which is bilaterally attached to the lateral or ventrolateral aspect of the solid hemispheres; (3) the lines of attachment or taeniae of the tela choroidea form the most important landmarks in the telencephalon of actinopterygians, indicating the sites where the greatly enlarged ventricular surface of the hemispheres ends and its reduced meningeal surface begins; (4) the meningeal surface of the telencephalon shows in most actinopterygians bilaterally a longitudinally oriented sulcus externus, the depth of which is generally positively correlated with the degree of eversion; (5) a distinct lateral olfactory tract, occupying a constant topological position close to the taenia, is present in all actinopterygians studied; and (6) this tract is not homologous to the tract of the same name in the evaginated and inverted forebrains of other groups of vertebrates. In the third and final section, the concept that the structural organization of the pallium in actinopterygians can be fully explained by a simple eversion of its walls, and the various theories, according to which the eversion is complicated by extensive shifts of its constituent cell groups, are discussed and evaluated. It is concluded that there are no reasons to doubt that the pallium of actinopterygian fishes is the product of a simple and complete eversion.

The arrangement of axons in a tract can have a specific effect on the organization of functional neuronal circuits. Here we describe olfactory bulb axons chronologically arranged in the lateral olfactory tract. Newly differentiated projection neurons over the whole olfactory bulb are similarly marked with transient expression of c-kit protein. Their axons are assembled together and project into the ventral superficial part of the tract, displacing the older axons. This special assembly of the axons explains the nontopographic relationships between the olfactory bulb and the lateral olfactory tract axons that have been described in previous studies and could possibly influence the subsequent selection of the olfactory target areas by these axons. J. Comp. Neurol. 475:247–260, 2004. © 2004 Wiley-Liss, Inc.

The nature of memory is a central issue in neuroscience. How does our representation of the world change with learning and experience? Here we use the transcription ofArcmRNA, which permits probing the neural representations of temporally separated events, to address this in a well characterized odor learning model. Rat pups readily associate odor with maternal care. In pups, the lateralized olfactory networks are independent, permitting separate training and within-subject control. We use multiday training to create an enduring memory of peppermint odor. Training stabilized rewarded, but not nonrewarded, odor representations in both mitral cells and associated granule cells of the olfactory bulb and in the pyramidal cells of the anterior piriform cortex. An enlarged core of stable, likely highly active neurons represent rewarded odor at both stages of the olfactory network.Odor representations in anterior piriform cortex were sparser than typical in adult rat and did not enlarge with learning. This sparser representation of odor is congruent with the maturation of lateral olfactory tract input in rat pups. Cortical representations elsewhere have been shown to be highly variable in electrophysiological experiments, suggesting brains operate normally using dynamic and network-modulated representations. The olfactory cortical representations here are consistent with the generalized associative model of sparse variable cortical representation, as normal responses to repeated odors were highly variable (∼70% of the cells change as indexed byArc). Learning and memory modified rewarded odor ensembles to increase stability in a core representational component.

Experiments were performed to investigate which bundle of the olfactory tract was essential for mediating feeding behaviour in crucian carp. Fish were divided in three groups: control fish, fish with only the lateral olfactory tracts (LOTs) intact and fish with the LOTs cut. The fish were maintained in physiological saline after surgery to preserve the remaining tracts and postoperative inspections revealed the functional status of the remaining tracts. With the injection of food odour into the aquaria the scores for various feeding behaviours--biting, snapping, mouth openings and vertical posture--were not significantly different between those of the control fish and the fish with the LOT intact. Those fish that had the LOT cut but the medial and lateral parts of the medial olfactory tract (mMOT, lMOT) intact had significantly lower feeding-related scores than the other two groups of fish. The results of the present study indicate that the LOT is necessary to maintain the full qualitative and quantitative extent of feeding behaviour in crucian carp.

During development, mitral cells, the major output neurons of the olfactory bulb, project their axons caudolaterally into the telencephalon and form the lateral olfactory tract (LOT). Two types of guidance cues have been suggested for this projection. First, a long-range factor Slit, which is secreted from the septum, repels mitral cell axons into a caudolateral direction. Second, the pathway of mitral cell axons contains a subset of neurons designated as lot cells, which guide the axons through short-range interactions. It is not clear how these two guidance cues relate to each other and how they share the physiological roles. Here we examined the behavior of mitral cell axons in organotypic culture on ectopic application of Slit and inhibition of endogenous Slit signaling. The results suggested that the short-range guidance cue in the LOT pathway functions independently from Slit. Furthermore, our results showed that removal of the septum and inhibition of Slit signaling did not affect the projection of mitral cell axons. Although the septum and exogenous Slit can repel olfactory bulb axons, our results cast doubts on the physiological relevance of the septum and endogenous Slit in guiding the projection of mitral cell axons.

The interaction between synaptic potentials generated by the activation of separate sets of associative fibres was investigated in the piriform cortex of an in vitro isolated guinea pig brain preparation. Restricted regions of the piriform cortex served by separate contingents of afferent fibres of the lateral olfactory tract were isolated surgically. The activity generated by these patches of cortex in response to afferent stimulation propagates to remote cortical regions along cortico-cortical associative fibres. Current source density (CSD) analysis of field potential laminar profiles evoked by lateral olfactory tract stimulation confirmed that the synaptic sinks induced by distinct associative fibre contingents converge on the apical dendrites of piriform cortex neurons in the superficial lb layer. Pairing between potentials evoked by activation of two separate sets of associative fibres resulted in an almost linear summation when the two responses coincided. For interstimulus intervals of

A perfusate collected from donor slices of the olfactory cortex of the brain of rats during tetanization of the lateral olfactory tract (100 imp/sec, 30 sec) induced prolonged changes in the amplitudes of various components of the focal potentials (FP) in recipient slices. When the perfusates are divided in relation to the reactions arising in the donor slices into three types, "potentiated," "depressive," and "nonpotentiated," the reactions of the recipient slices prove to be diverse. The potentiated perfusate induced the development of depression. The depressive induced potentiation. The reactions of the recipient slices to the nonpotentiated perfusate were indeterminate. The data obtained suggest the secretion of active substances during the electrical tetanization of donor slices. These factors are capable of inducing reactions in the recipient slices which the donor slices had "experienced."

Henry McIlwain is usually remembered for his major contributions to the discipline of neurochemistry. He also had a profound influence on electrophysiology by inventing and establishing the brain slice technique. This article describes some of his pioneering studies where he devised ways of preparing, both manually and mechanically (using the McIlwain tissue chopper), viable slices of mammalian cortical tissue and showed how these could be maintained in a brain slice chamber. His work with Choh-Luh Li (Li and McIlwain, 1957) on the first intracellular recording from brain slices and his work with Chosaburo Yamamoto (Yamamoto and McIlwain, 1966) describing the first study of synaptic transmission in brain slices are highlighted. In these studies, McIlwain started the use of brain slices to investigate functional anatomy, to study the effects of hypoxia and hypoglycaemia, to perform quantitative pharmacological analyses and to study synaptic plasticity: investigations which continue today to provide important insights into the functioning of the brain in health and disease.

The mammalian brain is the most complex organ in the body. It controls all aspects of our bodily functions and interprets the world around us through our senses. It defines us as human beings through our memories and our ability to plan for the future. Crucial to all these functions is how the brain is wired in order to perform these tasks. The basic map of brain wiring occurs during embryonic and postnatal development through a series of precisely orchestrated developmental events regulated by specific molecular mechanisms. Below we review the most important features of mammalian brain wiring derived from work in both mammals and in nonmammalian species. These mechanisms are highly conserved throughout evolution, simply becoming more complex in the mammalian brain. This fascinating area of biology is uncovering the essence of what makes the mammalian brain able to perform the everyday tasks we take for granted, as well as those which give us the ability for extraordinary achievement.

The structural features of calbindin-positive neurons were studied in the mouse main olfactory bulb (MOB). Calbindin-positive neurons were heterogeneous, including numerous periglomerular cells, a few granule cells, small to medium-sized interneurons in the external plexiform layer, and large short-axon cells located in the external plexiform layer, internal plexiform layer, granule cell layer and ependymal/subependymal layer. These large short-axon cells were also heterogeneous; some corresponded to classically identified short-axon cells such as Blanes cells, Golgi cells, horizontal cells and vertical cells, but some others appeared to be previously unidentified. A few faintly calbindin-positive presumed tufted cells were also encountered. Near the ependymal/subependymal layer of the MOB some calbindin-positive short-axon cells extended their dendritic processes more or less parallel to the sagittal plane, presumably corresponding to medullary cells named recently. In addition we encountered a few calbindin-positive horizontal cells in the internal plexiform layer extending their axons toward the lateral olfactory tract, one of which was confirmed to extend its axon into the lateral olfactory tract, indicating that they were presumed to be one of projection neurons. The present study revealed the diversity of calbindin-positive neurons in the mouse MOB and their particular structural properties hitherto unknown.

The spontaneous activity and impulse conduction velocities of mitral and tufted cells were compared in the entire main olfactory bulb of freely breathing, anesthetized rats. Single units in the mitral cell body layer (MCL) and external plexiform layer (EPL) were identified by antidromic activation from the lateral olfactory tract (LOT), electrode track reconstructions based on dye marking, and the waveform of LOT-evoked field potentials. Using the track reconstructions, EPL units were further subdivided into glomerular border (GB) and not at the glomerular border (notGB) cells. For conduction velocity, significant differences were only found between MCL and GB units and not between MCL and all EPL units or between MCL and notGB units. For spontaneous activity, no significant differences were found between the different unit groups regarding the mean, maximum, or relative maximum rate per 100-ms bin. By contrast, they showed a differential modulation of their firing activity by respiration. GB but not notGB units had a significantly higher mean rate during the respiratory cycle than MCL units with significantly more activity during inspiration. Thus, mitral and tufted cells are similar in their impulse conduction velocity and spontaneous activity, though the more superficially placed GB cells exhibit differences. A comparison of odor responses in these cell types in the companion paper also points to differences between mitral and superficial projection tufted cells.

Based on the results of recent electrophysiological and anatomical studies, we argue that the classical division of the entorhinal cortex (EC) into a superficial layer input station and deep layer output station is no longer tenable. We point out that the anatomical data suggest that the medial and lateral divisions of EC are separate, and recent studies of the propagation of signals originating in the lateral olfactory tract and perirhinal cortex to the EC [J. Neurophysiol. 83 (2000) 1924-1931; Biella and de Curtis, 2000) indicate that the lateral division is the input station, and the medial division the output station for information processed in the hippocampus and subiculum.

After amino acid discrimination training (Arg vs. Gln) in 5 groups of 2 fish the olfactory nerves and in 5 groups the lateral olfactory tracts were intracranially and bilaterally dissected. Immediately after this operation both groups of fish were unable to discriminate concentration differences and contaminated stimuli. Two weeks after the operation, following functional regeneration, both groups again were able to discriminate stimulus concentration differences and contaminations as they did before the operation. Therefore functional regeneration of the olfactory nerves (peripheral regeneration) and lateral olfactory subtracts (central regeneration) is highly specific.

The present study was aimed at determining the functionally essential size of the neuronal population in the central olfactory nervous system. Using conditioned rats who had learnt to avoid repellent (cycloheximide) solution by olfaction, varying degrees of injuries were made to the lateral olfactory tract, a major central olfactory pathway connecting the olfactory bulb to the olfactory cortex. After examining their olfactory ability to discriminate cycloheximide solution from water, intact bulbar projection neurons (mitral cells) with fiber connections to the olfactory cortex were quantified using a retrograde fiber tracing technique. The numbers of retrogradely labeled mitral cells from the rats with normal olfaction ranged between 20 and 92% of the control value, while those numbers from the anosmic rats ranged between 0 and 22%. We conclude that the functionally essential neuronal population is approximately one-fifth of the total in the central olfactory pathway, a presumed threshold value in terms of the ability to avoid cycloheximide solution by olfactory discrimination.

The early-generated neurons designated as lot cells specifically mark the future site of the lateral olfactory tract (LOT) and guide LOT axons. We investigated the mechanism of how lot cells develop and get localized in the LOT position. Lot cells differentiated from neuroepithelial cells in all regions of the neocortex but not from those in the ganglionic eminence in culture. Cell tracing analyses demonstrated that lot cells generated from the neocortex subsequently followed a tangential migration stream ventrally toward the LOT position. Mutant mouse embryos lacking the function of transcription factor Gli3 showed disturbances of the migration stream and translocation of lot cells in the dorsal telencephalon. These results reveal a new type of neuronal migration in the telencephalon and introduce an unexpected dramatic feature of the earliest regionalization of the telencephalon.

During development, mitral cell axons, the major efferents of the olfactory bulb, exhibit a protracted waiting period in the lateral olfactory tract (LOT) before giving off collateral branches and innervating the target olfactory cortex. To investigate the target invasion mechanism, a series of heterochronic and heterotopic cocultures of olfactory bulbs with various olfactory cortical strips were conducted. These experiments indicated that development of collateral branches is triggered by environmental cues but not by intrinsic mechanisms in mitral cells. The collateral-inducing cues are apparently different from the cues directing outgrowth of primary mitral cell axons. Coculture experiments also indicated that the target olfactory cortex undergoes a developmental change to become accessible to mitral cell fibers. Primary mitral cell axons, however, still preferred the LOT position over such accessible piriform cortex when encoutered both the locations. These results suggest that mitral cell projection comprises multiple steps which are controlled by various environmental cues. © 1999 John Wiley & Sons, Inc. J Neurobiol 38: 93–104, 1999

The role of the associative connections in the propagation of epileptiform discharges originating from an acute, localized epileptic focus in the anterior piriform cortex has been characterized recently in the in vitro isolated guinea-pig brain preparation. The present study demonstrates that the dorsal propagation of epileptiform synaptic potentials generated in APC is carried by long-projective associative fibres. Current source density analysis of the field potential profiles evoked by stimulation of the lateral olfactory tract has been utilized to describe the functional circuit activated in rostral and caudal regions of the piriform cortex, before and after the induction of a bicuculline epileptic focus in the anterior piriform cortex. Separate stimulation of the lateral olfactory tract at two sites, caudal and rostral to a tract incision, activates epileptiform potentials that are generated at the site of primary focus in the anterior piriform cortex and travel along associative fibres. Selective cutting of the long-projective associative fibres abolishes the epileptic associative potential in the cortical regions caudal to the section. The present study demonstrates directly that epileptiform potentials propagate along associative fibres to cortical regions that are synaptically related to the focus of origin. Such a pattern of propagation may sustain the generation of secondary foci in cortical regions remote from the primary epileptic focus.

Neurons, glia, and callosal axons operate as a “ménage à trois” in the development of the corpus callosum., The corpus callosum (CC) is the main pathway responsible for interhemispheric communication. CC agenesis is associated with numerous human pathologies, suggesting that a range of developmental defects can result in abnormalities in this structure. Midline glial cells are known to play a role in CC development, but we here show that two transient populations of midline neurons also make major contributions to the formation of this commissure. We report that these two neuronal populations enter the CC midline prior to the arrival of callosal pioneer axons. Using a combination of mutant analysis and in vitro assays, we demonstrate that CC neurons are necessary for normal callosal axon navigation. They exert an attractive influence on callosal axons, in part via Semaphorin 3C and its receptor Neuropilin-1. By revealing a novel and essential role for these neuronal populations in the pathfinding of a major cerebral commissure, our study brings new perspectives to pathophysiological mechanisms altering CC formation., Author Summary The largest commissural tract in the human brain is the corpus callosum, with over 200 million callosal axons that channel information between the two cerebral hemispheres. Failure of the corpus callosum to form appropriately is observed in several human pathologies and can result from defects during different steps of development, including cell proliferation, cell migration, or axonal guidance. Studies to date suggest that glial cells are critical for the formation of the corpus callosum. In this study, we show that during embryonic development, the corpus callosum, which was considered a neuron-poor structure, is in fact transiently populated by numerous glutamatergic and GABAergic neurons. With the use of in vitro graft experiments and of various transgenic mice, we demonstrate that neurons of the corpus callosum are essential for the accurate navigation of callosal axons. Moreover, we discovered that the guidance factor Semaphorin 3C, which is expressed by corpus callosum neurons, acts through the neuropilin 1 receptor to orient axons crossing through the corpus callosum. The present work therefore gives new insights into the mechanisms involved in axon guidance and implies that transient neurons work together with their glial partners in guiding callosal axons.

1. The reaction of neurons of a number of zones of the corticomedial grouping of structures of the AC has been identified in the time course of the estrous cycle. These may be combined into three groups on the basis of the features of structural-functional organization. The zones of the first group (the anterior amygdalar region, the nucleus of the lateral olfactory tract, zones of the anterior cortical nucleus, the basomedial nucleus) are found at the rostral pole of the AC, and are characterized by the presence of direct connections with the main olfactory bulb; the zones of the second group (the dorsomedial nucleus and the medial portion of the posterior cortical nucleus) are located in the posterior division of the AC and have direct connections with the accessory olfactory bulb; the zones of the third group (the central nucleus and the intercalated masses) are characterized by the presence of direct connections with the zones of the groups indicated above and with nuclei of the brain stem, and are located in the central zones of the AC. 2. A reaction of the neurons of the basolateral nucleus of the caudal level of the central division has been identified in the basolateral grouping of AC structures. 3. The results obtained demonstrate differences in the reactivity of neurons of the corticomedial and basolateral groupings of the AC in the time course of the estrous cycle.

The main afferent input to the olfactory cortex from the olfactory bulbs is via the lateral olfactory tract (LOT). The axons within the lateral olfactory tract are myelinated. On leaving the LOT, they lose their myelination as they fan out over the layer immediately beneath the pial surface to make en passant synaptic connections with dendrites from neurones within the olfactory cortex. Using the guinea-pig, a semiquantitative electron micrographical study was made of the density and dimensions of these unmyelinated axons and the varicosities they create. The unmyelinated axons were very fine (0.17 +/- 0.004 micron in diameter) and punctuated at 2 microns intervals by varicosities containing a single type of vesicle. The electrophysiological consequences of this close varicosity spacing is that axonal and varicosity membranes behave electrically as single units.

The origin of the centrifugal fibers to the olfactory bulb in the goldfish was examined by injecting a fluorescent dye, primuline, into the olfactory bulb by means of hydraulic pressure. Three to five days after the primuline injection, which was confined to the unilateral olfactory bulb, a large number of primuline-labeled perikarya appeared in two telencephalic areas on the ipsilateral side: the area ventralis telencephali pars dorsalis (Vd) and the ventral part of the area dorsalis telencephali pars lateralis (Dlv). No labeled cells were observed in the other olfactory bulb or in the contralateral telencephalic hemisphere or more posterior part of the brain. A combination of the primuline injection and the transection of either the medial or lateral olfactory tract showed that the main course of the centrifugal fibers was through the medial olfactory tract. These results may support Sheldon's opinion that the so-called tractus olfactorius ascendens, which corresponds to the medial part of the medial olfactory tract, is a centrifugal bundle originating from the cells in the nucleus medianus. The areas of the telencephalic hemisphere into which the olfactory bulbar fibers projected were also examined and compared with the originating areas of the centrifugal fibers. There was a considerable overlap between these two areas. This suggests a reciprocal connection between the olfactory bulb and the telencephalon.

A nutritional modulation of electrical mitral cell multiunit responses was studied in three groups of rats, with either a unilateral section of the olfactory peduncle (OP) or of the lateral olfactory tract (LOT), or with unilaterally damaged olfactory mucosa (zinc sulphate treatment). The control and lesion-side activity was chronically recorded in the bulbs of hungry and satiated animals receiving series of 10 identical stimulations with a food odor and odors non-associated to nutrition. Patterns of positive, negative and null responses were thus collected. In the control-side bulbs of the LOT and OP groups, as in intact animals, the percentage of positive responses was maximal in hungry rats receiving food odor, and minimal in satiated rats receiving isoamyl acetate, as a result of the nutritional modulation of responses. In the lesion-side bulbs of the LOT group, activation increased irrespective of the nutritional state of the animal and the nutritional meaning of the odorant. This shift was reproduced in the lesion-side bulbs of the OP group. In these animals, no nutritional modulation was observed, an effect ascribed to the disruption of activating fibers in the anterior limb of the anterior commissure (AAC). The zinc sulphate treated animals displayed a lack of olfactory responses in the treated-side bulbs, and no response modulation in the control-side bulbs, where the percentage of positive responses for non-alimentary odors was slightly increased, presumably as a consequence of the suppression of interbulbar inhibition. The results are discussed in terms of the quantity of olfactory information necessary for the centrifugal nutritional modulation to be released. The neuronal circuits subserving these various effects in the bulb are considered.

Olfactory bulb field potential and single unit responses to paired pulse stimulation of the lateral olfactory tract were observed in the rat. In agreement with previous reports, surgical levels of barbiturate anesthesia prolonged the period of diminution of the field potential responses to the test pulse relative to the effect seen under light anesthesia. Very deep barbiturate anesthesia (sufficient to depress the EEG) led to decreased responses to the primary pulse but augmented responses to the test pulse. Urethane and ether anesthesia produced augmented test responses without severely depressing the EEG and without producing a period of diminished test responses. Single unit recordings failed to show external plexiform layer units excited at the time of maximal augmentation of the field potential. Simultaneous single unit and field potential recordings showed that prolonged diminution of the field potential response was associated with prolonged suppression of unit responses to the test pulse, while augmented field potential responses were associated with decreased suppression of unit responses to the test pulse. These observations are most easily explained by the assumption of temporal facilitation in the synaptic output of mitral and tufted cells. This facilitation is masked by feedback inhibition under some conditions, particularly under barbiturate anesthesia.

Bilateral electrolytic lesions in the periamygdaloid piriform cortex of female albino rats produced marked disruptive effects on the acquisition of active avoidance responses in a 1-way as well as a 2-way test situation, significantly impaired passive avoidance behavior, and inhibited feeding in a novel environment. Lesions in each of the 6 major subdivisions of the amygdala (cortical, medial, central, intercalated, lateral, and basolateral nuclei) consistently produced facilitatory effects on active avoidance behavior in 1-way as 2-way situations. Passive avoidance behavior was impaired in animals with lesions in the central, intercalated, and basolateral nuclei. Damage to the anterior amygdaloid area or the the nuclei of the lateral olfactory tract did not reliably affect active or passive avoidance behavior.

Rats trained in an olfactometer were tested for retention of an odor detection and odor discrimination task after lesions of the olfactory peduncle. Large lesions of the peduncle, including transection of the lateral olfactory tract and anterior commissure resulted in severe deficits in retention and relearning but did not produce anosmia. Discrete lesions of the lateral olfactory tract had little or no effect on retention. The results indicate that the lateral and intermediate olfactory pathways are not essential for smell and suggest that significant olfactory function may be mediated by medial olfactory bulb projections.

Time of neuron origin in the anterior olfactory nucleus (AO) and nucleus of the lateral olfactory tract (NTOL) was determined autoradiographically in adult mice which received tritiated thymidine once during development. Each subdivision of AO has an individualized period and pattern of neuron origin. All subdivisions contain neurons which arise on E11; but the medial, dorsal, and external subdivisions complete their complement by E18 whereas posterior and lateral neurons continue to arise through P1. No gradients along the caudorostral axis were discerned. Neurons of NTOL arise early (E10-14), typical of large neurons and similar to those of the surrounding anterior amygdaloid area.

The effects of neuronal degeneration on benzodiazepine binding parameters were assessed following bilateral electrolytic lesions of rat brain lateral olfactory tracts. [3H]Flunitrazepam binding was measured in olfactory bulb homogenates 1, 7 and 14 days post-lesion. Specific [3H]flunitrazepam binding was significantly decreased two weeks after lesions. Diminution in binding was associated with a decreased population of sites (Bmax) rather than affinity alterations (KD). The time course for the loss of receptors is compatible with retrograde degeneration and suggests that specific benzodiazepine binding sites are in part located on mitral cell bodies.

Selective bilateral lesions of the lateral olfactory tract (LOT) and/or the anterior limb of the anterior commissure (AAC) were performed on male rats and their influence on performance of a simple task studied. Rats had to enter and run down an alley for water reward. Whatever the lesion, all the rats succeeded in learning the task but some differences appeared in comparison with intact and sham-operated rats. AAC rats acquired faster the task, whereas LOT rats and AAC + LOT rats took longer to reach the learning criterion.

The efferent projection fibers from the olfactory bulb have been studied using the Nauta-Gygax and the Fink-Heimer methods for degenerating axons after lesions were suitably placed by thermo-coagulation. From the olfactory bulb efferent fibers by way of the ipsilateral lateral olfactory tract end as preterminal and terminal fibers in the lateral, the external and the ventral segments of the anterior olfactory nucleus; the lateral two-thirds of the lateral olfactory tract, the cortical and the medial nuclei of the amygdaloid complex.

Resume The amygdaloid nuclei of the rat and mouse were studied, and the confusion in classification and nomenclature was revised and corrected. thereby certain new division and terminology being introduced. The main mass of the amygdala (AP) is divided into three parts. Fkh of them shows two subd visions, which seem to be genetically different. This is especially distinct in the intermedial part (Afi). The medial part (Apm) is small in dimension in rodents studied. The so-called ventromedial nuclear group, viz. the medial nucleus (D of Volsch, the cortical nucleus of Johnston, the nucleus B+D (basaler Spitzenkern) of Volsch. the nuclei B and D “of the same author. the nucleus of the lateral olfactory tract (D‘ of Volsch). were included all in the amygdala superficialis (Asf) in the present account, owing to its location and developmental aspect. Volsclt's nucleus B is not single mass of the same cytological character, as this is also the case with his nucleus D, the cell feature being pretty different from each other in the oral and caudal portions. In the house rat a fairly circumscribed mass of small cells, newly termed nucleus amygdalae parvocellularis corticalis. can be seen in the superficial amygdaloid area in the caudal half of it. In the mouse another type cells with fairly distinct arrangement were recognizable on the contrary in the anterior level of the amygdala direct caudal to the nucleus of the lateral olfactory tract, newly named ’nucleus arnygdalae magnocellularis corticalis' and likely homologous to the nucleus D” of Volsch. In comparison with another rodents these two nuclei can be regarded as specifically characteristic in the rat and mouse. The term ‘amygdala intercalata’ (Ain) has been given to those groups of small cells, which envelop the main mass of the amygdala especially in its oral half. In the anteromedial aspect of the amygdala it forms a large nucleus. nucleus intercalatus of Gurdjian. The central nucleus of Johnston and those found in the dorsal aspect of the main mass of the amygdala are summarized in supraamygdala (SA). Ln its oral portion and apart from the so-called central nucleus, which makes a prominent structure in rodents, a peculiar dense group of cells is found, to which the name nucleus supraamygdalae anterior is given. SA is evidently induced from the striatal matrix in an early embryonal period. Investigations on embryonal materials of the mouse show that both processes of pallial and non-pallial developments are intimately concerned with each other especially in the caudal part of the main amygdaloid mass, the anterior part of the latter being apparently formed by the forward growth of the posterior part. Through all embryonal stages it seems that non pallial elements, emerging from the ependymal layer of the ventricle, play a dominant role. This view is not in agreement to that of Holmgren and Johnston.

WE do not know whether two different types of secondary olfactory neurones exist. Classical anatomical studies have separated secondary olfactory neurones into two types: tufted cells and mitral cells1. Mitral cells form a discrete layer in the olfactory bulb and send their axons by way of the lateral olfactory tract (LOT) to ipsilateral cortical structures. Tufted cells are smaller than mitral cells and are scattered throughout the external plexiform layer. The efferent path of tufted cell axons is not clear. Previously, tufted cell axons were thought to cross by way of the anterior limb of the anterior commissure (AAC) and terminate in the contralateral olfactory bulb1, but recent anatomical studies2,3 do not confirm the entrance of tufted cell axons into the AAC. There are now at least two different views about the projection of tufted cell axons. Lohman and Mentink4 propose that tufted cell axons enter the LOT and that, therefore, at least some tufted cells may be considered displaced mitral cells. Valverde5, however, states that tufted cell axons do not leave the olfactory bulb.

The rhythmic potentials which occur in the olfactory bulb during odor stimulation (induced waves) were studied in rats anesthetized with urethane. Single-pulse electrical stimuli of the lateral olfactory tract were triggered from the onset of air flow through the nose and delayed to occur during or before the induced wave. These pulse stimuli had no effect on the amplitude of the induced wave. However, the timing of the induced wave was altered so that each successive response was reset into nearly constant phase relationship with the lateral olfactory tract pulse. Except at the highest odor intensities, there was no adaptation of the response under these conditions. The entrainment of the induced wave is probably a result of the strong inhibition produced in the mitral and tufted cells of the olfactory bulb following the lateral olfactory tract pulse. The entrainment is evidence in favor of the induced wave being produced by oscillations in the feedback circuit involving these neurons and their reciprocal dendrodendritic synapses with granule cells.

Immunocytochemical localization of specific neurotransmitters in the brain is becoming increasingly important in studies of maturation. We have used the trilaminar prepyriform cortex (PC) of rats to study the distribution, patterns and relative number of cells, fibers and terminals during postnatal development using antisera to cholecystokinin (CCK) and glutamic acid decarboxylase (GAD). Both antisera show distinct patterns of immunoreactivity at birth and subsequent periods of distinct changes in these patterns. CCK immunoreactivity is rare but present at birth mostly in layer II. There is a dramatic increase of CCK-labeled structures between postnatal (PN) days 6 and 9 and between PN 13 and 21. The adult pattern is observed by PN 21 with large numbers of labeled cells in layer II, numerous terminals in layers II and deep I and large immunoreactive fibers in the lateral olfactory tract. At birth GAD-immunoreactive terminals are present mainly in layer I, forming a distinct pattern of superficial and deep bands. Subsequent major changes occur in this pattern between PN 9 and 13 and again between PN 13 and 21. By PN 21 there appears to be a loss in deeper laminae of GAD positive terminals which are possibly replaced by the increasing numbers of CCK terminals in the same sublaminae. The adult pattern of GAD immunoreactivity is established by PN 21 with terminals and a few cells in layer I. Therefore, throughout development of the rat PC, there is a distinct complementary and changing distribution of GAD and CCK. Factors that may influence these changes in immunoreactivity are discussed.

The effects of the bilateral transection of the LOT on the patterns of 2-deoxyglucose uptake within the olfactory bulb and the olfactory projections were studied in adult rats. Animals were exposed to a pure neutral odor, ethyl acetoacetate (EAA) or to a biological alarming odor, fox odor. In intact animals, the patterns of glomerular activity elicited by EAA and fox odor appeared complex. An average number of 30–40 foci of 2-DG uptake was noted in each bulb and the optical density of the foci spread out according to a continuous gradient. These patterns were largely overlapping on the lateral aspect and the third-to-posterior part of the medial aspect of the bulb. Nevertheless, they were somewhat different and the spatial distribution of the darkest foci seemed particularly relevant for the pattern recognition. In lesioned animals, the same spatial distribution of the foci as in intact rats, was observed in the lateral and the medial aspects of the bulb. Nevertheless, lesioned animals presented some quantitative changes in their patterns of glomerular labeling. Moreover, these patterns appeared different according to the biological meaning of the odor tested. The bilateral transection of the LOT brought about a very strong decrease of the optical density in the direct olfactory projections. No evident change of 2-DG uptake was noted in the different tertiary olfactory projections. These 2-DG results confirm the anatomical data relating to the LOT projections.

Mating behavior in male hamsters depends on the sense of smell. Thus, complete transection of the lateral olfactory tract in adults eliminates mating. If the cut is made early in life, however, mating is spared. Partial section of the tract in adults does not affect mating, but similar cuts in the neonate lead to impaired mating performance later in life. Observed postsurgical rearrangements in the connections of axons in the lateral olfactory tract may explain both the sparing and the deterioration of function.

International audience; An original pathway of centrifugal acetylcholinesterase-positive fibres is described in the olfactory bulb of the rat. A dense network of positive fibres spreads out superficially at the boundaries of the lateral olfactory tract and the glomerular layer. These labelled fibres converge towards atypical glomerular structures lying close to the classical olfactory glomeruli. The atypical glomeruli are located dorsally at the medial border of the accessory olfactory bulb, in the area previously described as the "modified glomerular complex", and in the ventrolateral bulbar area. They structurally differ from typical glomeruli, as suggested by observations on semithin sections. The ultrastructural distribution of acetylcholinesterases into axonal and dendritic profiles, around and inside atypical glomeruli, is consistent with the hypothesis of centrifugal modulatory influences at this level. This study illustrates several new aspects of morphofunctional heterogeneity in the olfactory system. The glomerular layer of the main olfactory bulb can no longer be considered as morphologically and functionally uniform. Atypical glomeruli located in the mediodorsal and the ventrolateral boundaries of the glomerular layer are characterized by both structural features and an uncommonly high convergence of acetylcholinesterase-positive centrifugal fibres. Such areas might be involved in the processing of specific olfactory signals as demonstrated elsewhere for the "modified glomerular complex".

The functional development of inhibition in the rat olfactory bulb was examined in the present study. Inhibition of presumed mitral cell spontaneous activity following stimulation of the lateral olfactory tract was present by postnatal day 5, the youngest age tested. The duration of this inhibition was greatest in young animals, decreasing after postnatal day 15. Possible mechanisms of this enhanced inhibition in neonates were discussed.

In rats under alpha-chloralose or without general anesthesia the effect of a lateral olfactory tract stimulus on the caudate nucleus electric activity was explored by bipolar macroelectrodes. The stimulation effectiveness and the reactivity of recording sites to somatic stimuli were systematically tested. Under these conditions, no functional connection from the lateral olfactory tract to the caudate nucleus was demonstrated.