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We prospectively recruited 10 patients who presented with urinary retention as a neurological deficit that was attributable to lateral medullary infarction. Of these, 9 patients underwent a urodynamic study, which demonstrated detrusor underactivity of the bladder in 7 patients. Urinary retention developed mainly when the lesions involved the lateral tegmentum of the middle or caudal medulla. We concluded that interruption of the descending pathway from the pontine micturition center to the sacral spinal cord in the lateral medulla was responsible for the development of urinary retention.

Cross-correlation of neural discharges was used to investigate the connections between expiratory bulbospinal neurons (EBSNs) in the caudal medulla and expiratory motoneurons innervating thoracic and abdominal muscles in anesthetized cats. Peaks were seen in the cross-correlation histograms for around half of the EBSN-nerve pairs for the following: at T8, the nerve branches innervating internal intercostal muscle and external abdominal oblique muscle and a more distal branch of the internal intercostal nerve; and at L1, a nerve branch innervating internal abdominal oblique muscle and a more distal branch of the ventral ramus. Fewer peaks were seen for the L1 nerve innervating external abdominal oblique, but a paucity of presumed α-motoneuron discharges could explain the rarity of the peaks in this instance. Taking into account individual EBSN conduction times to T8 and to L1, as well as peripheral conduction times, nearly all of the peaks were interpreted as representing monosynaptic connections. Individual EBSNs showed connections at both T8 and L1, but without any discernible pattern. The overall strength of the monosynaptic connection from EBSNs at L1 was found to be very similar to that at T8, which was previously argued to be substantial and responsible for the temporal patterns of expiratory motoneuron discharges. However, we argue that other inputs are required to create the stereotyped spatial patterns of discharges in the thoracic and abdominal musculature.

We investigated sound production and the sonic motor system in the Pineconefish, Monocentris japonica. The hand-held Pineconefish produced one type of sound (main frequencies: 100–600 Hz) in both water and air. The sonic organ consists of the swimbladder and a pair of extrinsic sonic muscles originating from exoccipital of the cranium and supracleithrum and inserting on the anterodorsal surface of the swimbladder and partly on vertebrae. The sonic muscle is innervated by occipital nerve branches, not the spinal nerves. Injections of wheat germ agglutinin-conjugated horseradish peroxidase into the sonic muscle resulted in labeled sonic motor neurons ipsilateral to the injections. The labeled neurons were located in the ventral zone of the caudal medulla oblongata, forming a column of sonic motor neurons (or the sonic motor nucleus) from the level of the vagal nerve root to the rostral part of the third ventral root of the occipital nerve. The total number of motor nerve fibers contained in the rig...

"Diffuse noxious inhibitory controls" (DNIC) refer to the observation that the activity of multi-receptive neurons of the spinal cord and trigeminal system can be strongly suppressed by an intensive pain stimulus outside their peripheral receptive field. This effect represents a neurophysiologically well-established animal model of endogenous pain modulation that has been consistently demonstrated across different species. Electrophysiological and anatomical data support the view that DNIC are sustained by a largely independent spino-bulbo-spinal loop that critically involves the caudal medulla. It is assumed that, corresponding to the animal model, the perceptive effects of 'heterotopic noxious conditioning stimulations' (HNCS) in humans are predominantly based on the DNIC mechanism. This review focusses on DNIC and HNCS including similarities, divergences and their potential clinical relevance.

The descending control of respiratory-related motoneurones in the thoracic spinal cord remains the subject of some debate. In this study, direct connections from expiratory bulbospinal neurones to identified motoneurones were investigated using spike-triggered averaging and the strengths of connection revealed were related to the presence and size of central respiratory drive potentials in the same motoneurones. Intracellular recordings were made from motoneurones in segments T5–T9 of the spinal cord of anaesthetized cats. Spike-triggered averaging from expiratory bulbospinal neurones in the caudal medulla revealed monosynaptic EPSPs in all groups of motoneurones, with the strongest connections to expiratory motoneurones with axons in the internal intercostal nerve. In the latter, connection strength was similar irrespective of the target muscle (e.g. external abdominal oblique or internal intercostal) and the EPSP amplitude was positively correlated with the amplitude of the central respiratory drive potential of the motoneurone. For this group, EPSPs were found in 45/83 bulbospinal neurone/motoneurone pairs, with a mean amplitude of 40.5 μV. The overall strength of the connection supports previous measurements made by cross-correlation, but is about 10 times stronger than that reported in the only previous similar survey to use spike-triggered averaging. Calculations are presented to suggest that this input alone is sufficient to account for all the expiratory depolarization seen in the recorded motoneurones. However, extra sources of input, or amplification of this one, are likely to be necessary to produce a useful motoneurone output.

A previously healthy 20 year-old male presented with headache, acute pulmonary oedema and left ventricular dysfunction requiring intensive care admission. Cardiorespiratory symptoms resolved within three days; however, the patient complained of persistent headache and had gait unsteadiness. Magnetic resonance imaging showed a large demyelinating lesion in the caudal medulla with scattered cerebral plaques. The patient was subsequently diagnosed with multiple sclerosis. This case describes a rare initial presentation of multiple sclerosis with acute pulmonary oedema and cardiac dysfunction secondary to a lower brainstem lesion.

Investigators have demonstrated pressor areas in the medullas of various species. The present study precisely localized the pressor area in the caudal medulla of the rat and determined its projections to the caudal and rostral ventrolateral medulla. The caudal medulla first was mapped grossly in rats with injections (30 nl) of glutamate (30-, 15-, and 7.5-nmol doses) placed 0.5, 1.0, and 1.5 mm caudal to the calamus scriptorius, 1.0, 1.5, and 2.0 mm lateral to the midline, and 1.8, 1.7, and 1.6 mm ventral to the dorsal medullary surface, respectively, and their arterial pressures were recorded. One of these nine injections showed significant increases in arterial pressure. We micromapped this area with a total of 27 injections of glutamate (10 nl; 5 nmol) placed 300 μm apart at 3 different dorsoventral levels. This micromapping study pinpointed the precise location of caudal pressor area (CPA) neurons in a restricted region lateral to the caudal end of the lateral reticular nucleus and ventromedial to the medullary dorsal horn near the level of the pyramidal decussation. Injections of glutamate into this spot, 1.0 mm caudal to the calamus scriptorius, 2.0 mm lateral to the midline, and 1.7 mm ventral from the dorsal surface of the medulla, induced significant increases in arterial pressure. The neuroanatomic connections of neurons in the CPA to the ventrolateral medulla were then investigated with iontophoretic injections of either the anterograde tracer biotinylated dextran amine (BDA) made into the CPA or the retrograde tracer FluoroGold (FG) injected into either the caudal or rostral ventrolateral medulla. BDA injections resulted in bouton-laden fibers throughout both caudal and rostral portions of the ventrolateral medulla. Either of the FG injections resulted in numerous spindle-shaped neurons interspersed between the longitudinal fiber bundles running through the CPA area. The proximity of the CPA neurons to the A1 catecholaminergic cell group is discussed.

Les stimulations nociceptives punctiformes generalement utilisees au cours des etudes de la nociception chez l’animal sont a l’evidence tres differentes des lesions tissulaires, parfois etendues, rencontrees en pratique clinique. Nous avons tente de preciser le role de la sommation spatiale dans l’integration medullaire de l’information nociceptive en etudiant les effets d’une gamme de stimulations thermiques nociceptives interessant des surfaces croissantes (1.9 a 18 cm2), dont l’intensite et la duree etaient par ailleurs constantes. Des neurones a convergence possedant un champ peripherique excitateur situe sur l’extremite de la patte posterieure ipsilaterale ont ete enregistres au niveau lombaire chez des rats anesthesies. La frequence de decharge des neurones augmente avec la taille du stimulus lorsque de petites surfaces sont concernees mais decroissent lorsque la surface de stimulation depasse 4.8 cm2. Cette decroissance, a priori paradoxale, resulte de la mise en jeu de controles inhibiteurs descendants car elle n’est pas observee chez des animaux dont la moelle cervicale a ete prealablement sectionnee.

Microvascular decompression (MVD) of cranial nerves has become an established treatment for trigeminal and (vago)glossopharyngeal neuralgia and for hemifacial spasm. The authors present the case of a 64-year-old man who had a 3.5-year history of severe, drug-resistant hemibody pain with sensory and autonomic disturbance. The ipsilateral trigeminal, cochlear, and glossopharyngeal function also was affected. The contralateral posterior inferior cerebellar artery was seen on magnetic resonance imaging to be indenting the caudal medulla anterolaterally, causing displacement. After MVD of the medulla, there was an immediate and complete resolution of the pain and almost complete resolution of the sensory and autonomic disturbances. The pain later recurred mildly and transiently. The residual symptoms had resolved by 2 years.

In 1995, we discovered a new pathway in the cat, which originates from the nucleus retroambiguus (NRA) and terminates in a distinct set of lumbosacral hindlimb, axial, and pelvic floor motoneuronal cell groups [VanderHorst VG.JM, Holstege G (1995) Caudal medullary pathways to lumbosacral motoneuronal cell groups in the cat: evidence for direct projections possibly representing the final common pathway for lordosis. J Comp Neurol 359:457-475]. The NRA is a compact group of interneurons located laterally in the caudal medulla oblongata. Its projection to lumbosacral moloneurons is thought to represent the final common pathway for male mounting and for female receptive or lordosis behavior. However, females only display lordosis behavior when they are in estrus, which suggests that the NRA-lumbosacral pathway is only active during estrus. This raised the question of whether estrogen affects this pathway. The effect of estrogen on the NRA-lumbosacral projection was studied light microscopically, using wheat-germ agglutinin horseradish peroxidase (WGA-HRP) as a tracer. The rubrospinal pathway served as control. The density of labeled NRA fibers in their target hindlimb motoneuronal cell groups appeared abundant in estrous and very weak in nonestrous cats. Such differences were not found in the rubrospinal pathway. For electron microscopical study, the NRA projection to the semimembranosus motoneuronal cell group was selected. In this cell group, an almost ninefold increase of labeled profiles was found in estrous versus nonestrous cats. Moreover, the semimembranous motoneuronal cell group contained labeled growth cones in estrous, but not in nonestrous, cats. The present study is the first to show that estrogen induces axonal outgrowth of a precisely identified pathway in the adult mammalian central nervous system. The possible mechanisms underlying this outgrowth are discussed.

Upbeat nystagmus (UBN) is typically increased with upward gaze and decreased with downward gaze. We describe a patient with acute multiple sclerosis who developed primary position UBN with a linear slow phase waveform, in which the velocity of nystagmus was intensified in downward gaze and decreased during upward gaze. Brain MRI showed high signal lesions in the paramedian dorsal area of the caudal medulla encompassing the most caudal part of the perihypoglossal nuclei. Clinicians should be aware of possibility of a caudal medullary lesion in a patient with UBN, especially when the velocity of the UBN is increased in downward gaze.

A comparison was made of β-endorphin (B-END) concentrations versus post-translation products during the perinatal period in the hypothalamus and the caudal medulla oblongata. The concentration of B-END-like immunoreactivity did not differ statistically between embryonic day 21 (E21) and postnatal day 1 (P1) in either area. There were significant differences in forms, with a shift from larger precursors at E21 to smaller peptides at P1, with the predominant form of B-END being the 31 residue form at E21 in both regions. B-END varied between the two regions at P1, the 27-26 residue predominant in the hypothalamus, and the 31 residue in the caudal medulla.

Migraine is a common, disabling disorder one of whose core manifestations is activation, or the perception of activation, of nociceptive trigeminal neurons. Neurons in the most caudal medulla and dorsal horns of the two upper cervical cord segments receive input from trigeminally innervated structures and from nociceptive afferents in the distribution of C2, the trigeminocervical complex (TCC). TCC neurons project to thalamus and are influenced by neurotransmitters that have been shown to be involved in migraine, and by brainstem modulatory structures implicated in migraine by brain functional imaging studies. Studying the physiology and pharmacology of these systems will enhance understanding of migraine and related primary headache disorders.

In experiment 1, quantitative regional comparisons of the antinociceptive and cardiovascular responses produced by electrical stimulation in the caudal medulla, including regions such as the nucleus tractus solitarius (NTS), nucleus reticularis ventralis (NRV), nucleus reticularis gigantocellularis (NRGC), nucleus reticularis paragigantocellularis (NRPGC), nucleus raphe obscurus (NRO), and medial portions of the lateral reticular nucleus (LRN), were made in the rat. Electrical stimulation in all of these regions resulted in inhibition of the nociceptive tail-flick reflex, although the threshold intensity for inhibition was greater for sites in NTS compared to many sites ventral to the NTS. Antinociception was generally accompanied by an increase in mean arterial blood pressure, with the exception of sites in the NRO, where depressor responses were evoked by stimulation. Detailed comparisons between the NTS and NRV revealed that greater intensities of electrical stimulation were required to produce antinociception for sites in the NTS as compared to the NRV. There were no significant differences in threshold intensities for antinociception as a function of rostrocaudal subdivisions of the NTS, but the lateral subdivision of the NTS was significantly more efficacious than the medial subdivision. This mediolateral difference within NTS was primarily due to stimulation in medial sites producing overt movements in some animals, probably due to stimulation of adjacent midline nuclei or pathways. Within the NRV, thresholds for inhibition of the tail-flick reflex were greater for sites in the dorsal subdivision as compared to the ventral subdivision, which contains spinopetal projections from the NRM. The slopes of the lines of recruitment for inhibition of the tail-flick reflex at stimulation sites in either the NTS or NRV were both very steep, similar to other forms of antinociception. In experiment 2, the pulse duration of electrical stimulation was varied for sites of stimulation in the lateral NTS and NRV to generate strength-duration curves. This experiment confirmed that stimulation sites in the lateral NTS required greater current intensities to inhibit the tail-flick reflex than sites in the NRV. However, the chronaxies derived from the strength-duration functions for the NTS or NRV were both approximately 170 μsec, indicating that the antinociceptive effects in these regions may not be exclusively due to the stimulation of fibers of passage. These results are discussed in terms of the role of the NTS, NRV, and caudal medulla in the modulation of nociceptive responses and cardiovascular function.

During a 12-month period (1998–1999), microscopic evidence of neuroaxonal dystrophy (NAD) in medullae oblongata of raccoons ( Procyon lotor) was observed in 17/39 (47% prevalence in adults) from Iowa, USA. Three of the animals were kits (res in the brain were negative. Spongiotic areas often contained axonal spheroids. Degenerate neurons and axons occasionally contained amphophilic periodic acid-Schiff-positive granular material. There was a paucity of inflammatory cells in the affected areas. Since lesions were not present in kits, were either absent or mild in young adults, and were severe in older raccoons, the findings may be related to advancing age. Neuroaxonal dystrophy has not been previously reported in raccoons. Retrospective examination of raccoon brains from the eastern and northwestern areas of the country revealed very low prevalence of NAD. Because of the apparently high prevalence of this condition at this geographic location, factors other than age (genetic, nutritional, and/or environmental) may influence this degenerative process in the brains of raccoons in Iowa.

Gall, Olivier, Didier Bouhassira, Djamel Chitour, and Daniel Le Bars. Involvement of the caudal medulla in negative feedback mechanisms triggered by spatial summation of nociceptive inputs. J. Neurophysiol. 79: 304–311, 1998. In the rat, applying noxious heat stimuli to the excitatory receptive fields and simultaneously to adjacent, much larger, areas of the body results in a surface-related reduction in the responses of lumbar dorsal horn convergent neurons. These inhibitory effects induced by spatial summation of nociceptive inputs have been shown to involve a supraspinally mediated negative feedback loop. The aim of the present study was to determine the anatomic level of integration of these controls and hence to ascertain what relationships they might share with other descending controls modulating the transmission of nociceptive signals. The responses of lumbar convergent neurons to noxious stimulation (15-s immersion in a 48°C water bath) applied to increasing areas of the ipsilateral hindlimb were examined in several anesthetized preparations: sham-operated rats, rats with acute transections performed at various levels of the brain stem, and spinal rats. The effects of heterotopic noxious heat stimulation (tail immersion in a 52°C water bath) on the C-fiber responses of these neurons also were analyzed. The electrophysiological properties of dorsal horn convergent neurons, including their responses to increasing stimulus surface areas, were not different in sham-operated animals and in animals the brain stems of which had been transected completely rostral to a plane −2.8 mm remote from interaural line (200 μm caudal to the caudal end of the rostral ventromedial medulla). In these animals, increasing the stimulated area size from 4.8 to 18 cm2 resulted in a 35–45% reduction in the responses. In contrast, relative to responses elicited by 4.8 cm2 stimuli, responses to 18 cm2 were unchanged or even increased in animals with transections at more caudal level and in spinal animals. Inhibitions of the C-fiber responses elicited by heterotopic noxious heat stimulation were in the 70–80% range during conditioning in sham-operated animals and in animals with rostral brain stem transections. Such effects were reduced significantly (residual inhibitions in the 10–20% range) in animals with transections >500 μm caudal to the caudal end of the rostral ventromedial medulla and in spinal animals. It is concluded that the caudal medulla constitutes a key region for the expression of negative feed-back mechanisms triggered by both spatial summation of noxious inputs and heterotopic noxious inputs.

The nucleus retroambiguus (NRA) is a group of premotor neurons at the transition between brainstem and spinal cord. It projects to certain motoneuronal cell groups, among which is a distinct set of motoneurons in the lumbar enlargement innervating muscles including iliopsoas, adductor longus, and hamstrings. To find out whether these NRA-motoneuronal projections are monosynaptic, injections of wheat germ-agglutinin horseradish peroxidase (WGA-HRP) into the NRA were combined with injections of cholera toxin subunit b (CTb) into the hamstring muscles. Electron microscopical examination revealed that the NRA terminal profiles make monosynaptic contacts with dendrites of motoneurons innervating these muscles. The NRA terminal profiles formed asymmetrical synapses, and contained spherical and a few dense core vesicles. These findings provide evidence of monosynaptic NRA-hindlimb motoneuronal projections which are likely to be excitatory. (C) 1997 Elsevier Science Ireland Ltd.

In 1995, we discovered a new pathway in the cat, which originates from the nucleus retroambiguus (NRA) and terminates in a distinct set of lumbosacral hindlimb, axial, and pelvic floor motoneuronal cell groups [VanderHorst VGJM, Holstege G (1995) Caudal medullary pathways to lumbosacral motoneuronal cell groups in the cat: evidence for direct projections possibly representing the final common pathway for lordosis. J Comp Neurol 359:457-475]. The NRA is a compact group of interneurons located laterally in the caudal medulla oblongata. Its projection to lumbosacral motoneurons is thought to represent the final common pathway for male mounting and for female receptive or lordosis behavior. However, females only display lordosis behavior. However, females only display lordosis behavior when they are in estrus, which suggests that the NRA-lumbosacral pathway is only active during estrus. This raised the question of whether estrogen affects this pathway. The effect of estrogen on the NRA-lumbosacral projection was studied light microscopically, using wheat-germ agglutinin horseradish peroxidase (WGA-HRP) as a tracer. The rubrospinal pathway served as control. The density of labeled NRA fibers in their target hindlimb motoneuronal cell groups appeared abundant in estrous and very weak in nonestrous cats. Such differences were not found in the rubrospinal pathway. For electron microscopical study, the NRA projection to the semi-membranosus motoneuronal cell group was selected. In this cell group, an almost ninefold increase of labeled profiles was found in estrous versus nonestrous cats. Moreover, the semimembranous motoneuronal cell group contained labeled growth cones in estrous, but not in nonestrous, cats. The present study is the first to show that estrogen induces axonal outgrowth of a precisely identified pathway in the adult mammalian central nervous system. The possible mechanisms underlying this outgrowth are discussed.

Eighty-four neurons in the caudal ventrolateral medullary reticular formation were antidromically activated by the stimulation of the dorsolateral funiculus in 49 urethane-anesthetized rats. Of 76 neurons, 37 had no spontaneous discharge. Of the neurons that had spontaneous discharges, 80% had firing rates between 0.1 and 15 Hz. The average conduction velocity, determined among 70 neurons, was 15.20 ± 1.23 m/s, and 87% had conduction velocities within the range of 2–30 m/s. This study further confirms the existence of spinally-projecting neurons in the lateral reticular nucleus (LRN) of the caudal medulla, and some of them are probably responsible for the descending controls of nociception from the LRN.

Albrecht, U., Lametschwandtner, A., Adam, H. 1980. The vascularization of the anuran brain. Rhombencephalon and medulla spinalis. A scanning electron microscopical study of vascular corrosion casts. (Department of Zoology, University of Salzburg, Austria.) — Acta zool. (Stockh.) 61 (4): 239–246. The vascularization of the rhombencephalon and the medulla spinalis of Bufo bufo (L.) is demonstrated by scanning electron microscopy of vascular corrosion casts. The arterial supply of the rhombencephalon is performed by central arteries. The same is shown in the medulla spinalis. The venous pathways are represented by venae craniales occipitales and by a posterior and bulbar group of the encephaloposthypophysial portal vein, by veins draining into the venae craniales occipitales, by venae spinales ventrales (for the rostral regions of the medulla) and by venae spinales laterales (in the caudal medulla). In the regions examined so far a centrifugal course of the arterial vessels is reported.

Catecholamine levels and turnover have been studied in 5 week old male genetically hypertensive (LH) and normotensive (LN) rats of the Sprague-Dawley Lyon strain. The results demonstrate increased hypothalamic adrenaline levels and a reduced adrenaline turnover in the dorsal midline of the medulla oblongata (DCMO) in the LH rats compared with LN control rats. The reduction of adrenaline turnover in the DCMO may contribute to the development of spontaneous hypertension.

Injections of tritiated l -leucine were placed in the reticular formation of the medulla, the spinal trigeminal and lateral reticular nuclei of cats and silver grain accumulations in the inferior olivary nucleus were demonstrated by autoradiography. Cells of the reticular formation located at the junction of nuclei reticularis magnocellularis and reticularis parvocellularis in the rostral medulla and within nucleus reticularis ventralis in the caudal medulla contribute four distinct projections to the olive. Three projections are distributed ipsilaterally in the caudal part of the medial accessory olive, at mid-level of the dorsal accessory olive and in the ventrolateral bend of the principal olive, at rostral levels. There is also a small contralateral projection to the caudal part of the medial accessory olive. The spinal trigeminal nucleus sends crossed projections to the rostral part of the dorsal accessory olive and adjacent ventral lamella as well as to the caudal part of the medial accessory olive. The lateral reticular nucleus sends an extensive ipsilateral projection to the caudal part of the medial accessory olive and provides a small contribution to the same subdivision, contralaterally. All these projections converge with other known afferents to the olive.

The central noradrenaline (NA) and adrenaline (A) turnover in 15–16-week-old stroke prone, spontaneously hypertensive (sp-SH) female rats in an advanced stage of hypertension was found to differ from that of normotensive Wistar-Kyoto (WKy) control rats. The catecholamine (CA) levels were measured after inhibition of dopamine-β-hydroxylase (DBH) or of phenylethanolamine- N -methyltransferase (PNMT). In the hypertensive rats the dopamine (DA) and NA levels and the NA turnover were reduced in the hypothalamus, while in the dorsal part of the caudal medulla oblongata NA levels and A turnover were reduced. Changes in hypothalamic DA and NA mechanisms and in A mechanisms in medulla oblongata may therefore be of importance in the blood pressure regulation of sp-SH rats.

Using the retrograde tracer technique with horseradish peroxidase (HRP), attempts were made to determine the cells of origin and the descending pathway of the tegmentoreticular projections in order to give an anatomical substrate for the physiological phenomenon of the postural atonia observed during paradoxical sleep (PS) in the cat. The HRP was injected into various parts of the pontomedullary reticular formation (RF) including the caudal raphe nuclei, nucleus (n.) reticularis gigantocellularis (Gc), n. reticularis magnocellularis (Mc), and other pontomedullary structures adjacent to the Mc. The results indicated that the HRP injection into the Mc, particularly its caudal and lateral two-thirds, resulted in specific labeling of cells located in an area just medial to the LCα together with those in the most medial part of the LCα. Bilateral lesions of these pontine structures have been reported to suppress the atonia otherwise observed during PS in the normal cat. In addition to the HRP labeled cells, we have also observed HRP filled fiber bundles directed to labeled cells in the medial part of the LCα and immediately adjacent tegmental RF area. The same course of HRP labeled fiber bundles was also observed together with HRP labeled cells in the Mc after HRP injections into the medial part of the LCα area, indicating the existence of an interconnection between the LCα area and the Mc. The location of the tegmentoreticular pathway corresponded to that of the lesions effective to suppress the muscular atonia during PS. HRP injections into the caudal medulla caudal to the Mc, on the other hand, resulted in no or almost no HRP labeled cells in the area medial to the LCα, in spite of the presence of HRP containing neurons in other parts of the pontomedullary RF areas, showing that the tegmentoreticular projections as described above terminated almost exclusively in the Mc.

Thalamic projections from the caudal medulla of the cat were examined using the method of retrograde axonal transport of horseradish peroxidase (HRP). Injections were made unilaterally in various thalamic regions. Large injections labeled cells in the subnuclei: zonalis (Vcz), gelatinosus (Vcg), magnocellularis (Vcm), reticularis dorsalis (Vcrd) and ventralis (Vcrv) medullae oblongatae. The largest number of labeled cells were in Vcz, Vcrd and Vcrv. Most of the labeled cells in Vcz and Vcrd were contralateral to the injection site, although the labeled cells in the Vcrv were bilateral. Small injections were made into the medial, lateral and dorsal regions of the nucleus ventralis posteromedialis (VPM), rostral regions of the posterior nuclei (POm and PO1), caudal POm, the nucleus centralis lateralis (CL) and the center median-parafascicular nuclear complex (CM-Pf). Most of the neurons in Vcz were found to project to the medial VPM and some to the caudal POm. A small number of cells in the Vcrd project to the medial VPM, but a large number project to the caudal POm and CM-Pf complex. The largest number of neurons projecting to the CM-Pf complex was present in Vcrv, where the labeled cells were bilateral. The types of trigeminothalamic projecting cells and the sizes of their somata were observed for different subnuclei and a considerable difference was found to exist among the subnuclei. This anatomical differentiation of the trigeminothalamic projections probably reflects a functional specialization of neuronal location since the functional properties of neurons vary according to their locations.

The subdiencephalic rat brain was mapped for sites capable of mediating prostaglandin-induced pyrexia. In conscious rats, PGE 1 , 200 ng in a volume of 1 ωl, was injected unilaterally into 412 sites between the midmesencephalon and the caudal medulla. Injections into only 12 sites caused a reproducible, short-latency core temperature increase of at least 0.5°C. None of these was located in the paramedian brainstem, which was considered a likely site of PGE 1 action because of the presence there of thermosensitive and pyrogen-sensitive neurons. Rather, the reactive loci were found in the hippocampus (5 sites) and in the vicinity of the cochlear nuclei (7 sites). Injections into only 2 sites in the latter region failed to produce pyrexia. In the hippocampus, however, injections at 31 sites in the same frontal planes as the reactive loci produced no effect. The possibility that the active hippocampal sites were associated with a distribution of injectate to PGE 1 -sensitive neurons located within hippocampal cleavage planes rather than in a circumscribed region is discussed.

ALESSI, N. E. AND P. QUINLAN. Postnatal development of ACTH and a-MSH in the medulla oblongata of rat: a-MSH i.s the predominant peptide. PE PTIDES 6: Suppl. 2, 137-141, 1985.-ACTH and a-MSH levels were measured by radioimmunoassays in extracts of the caudal medulla oblongata of developing rats on postnatal (P) days 1-42 at 7 day intervals, and in adult rats. From PI to adulthood, ACTH increased > ! 1-fold from 7.2_ + 1.9 fmol to 82.4_+ 12.6 fmol per medulla section (mean_+ S.E.M.). In comparison, a-MSH increased >7-fold from 68.75_+ 11.0 fmol to 491 _+97.8 fmol during this time period. ACTH/p.g of soluble protein decreased during postnatal development from 0.006_+0.01 to 0.005_+0.001 fmol//zg of protein and a-MSH increased from 0.06_+0.01 fmol//zg of protein to 0.11 -+0.009 fmol//xg of protein between P1 and P7, decreased to 0.015_+0.003 fmol/#g of protein by P42 and increased to 0.03-+0.006 fmol/protein per unit protein by adulthood. These data indicate a significant shift in the levels of a-MSH detected during development with a decrease in the concentration of material occurring from early postnatal development (P1-P7) to adulthood, which does not appear to be solely related to a regional increase in protein. These studies, as well as radioimmunoassays for ACTH and a-MSH in combination with sizing chromatography of pooled extracts at P1. P7 and the adult, demonstrated the predominance of a-MSH at all ages. ACTH te-MSH Medulla oblongata Postnatal development Nucleus tractus solitarius

Two-color immunoperoxidase staining has been used to localize substance P (SP)-immunoreactive processes on neurons in the caudal medulla that exhibited both serotonin (5HT)- and SP-immunoreactivity (5HTI/SPI cells). The punctate SP-immunoreactive processes were present on 5HTI/SPI cells in the raphe nuclei and ventral reticular formation. This close association suggests that activity in bulbospinal 5HT/SP pathways, which can influence sympathetic preganglionic neurons, may be affected by the release of SP in the brainstem.

The mode of termination of primary afferent fibers within the cat trigeminal nucleus caudalis was investigated by means of the transganglionic transport of horseradish peroxidase (HRP). Several types of laminar-related labeling were observed, depending upon the survival time after HRP application. At the earliest survival time (28–34 h) the highest density of labeling was found in laminae I and II. At 2 and 3 days survival laminae III and IV were heavily labeled, in addition to laminae I and II where the amount of labeling was greatly increased in lamina I, but not in lamina II. At 5 days survival time an abrupt drop of labeling occurred in laminae I and II, while this pattern was not predominant in laminae III and IV. In lamina V the pattern of labeling was less intense and not changeable through all survival times observed. These findings indicating a differentiation of the primary afferent terminals have good correspondence with a functional specialization of neuronal locations since the functional properties of neurons vary according to their locations.

The reticular formation of the brain stem is the most ancient part of the brain and the one part that is absolutely necessary to the life of the organism. It consists of large numbers of neurons and fibers, and exclusive of the adjacent cranial nerve nuclei, long ascending and descending tracts, and a few large nuclear masses such as the olives, nucleus ruber, and substantia nigra, it constitutes the core of the brain stem. It is generally thought of as extending from the caudal medulla to the interface between mesencephalon (midbrain) and diencephalon (thalamus-hypothalamus). However, a series of cell masses clustered in the medial portions of the thalamus continue forward, forming the thalamic nonspecific system and, as such, can be thought of as the reticular formation of the thalamus.

Experiments were conducted in urethan-anesthetized rabbits to determine whether vasomotor effects elicited by activation or inhibition of the caudal ventrolateral medulla depend on gamma-aminobutyric acid (GABA)ergic, glycinergic, or alpha-adrenergic receptors in the region of the rostral ventrolateral medulla, which contains the bulbospinal sympathoexcitatory neurons. Bilateral injection of bicuculline methiodide into the rostral medulla caused a dose-related reduction in the fall in arterial pressure and in the inhibition of renal sympathetic nerve activity normally elicited by chemical stimulation of neurons in the caudal medulla using local injection of L-glutamate. When both bicuculline and muscimol were injected into the rostral medulla at the same time, resting arterial pressure was maintained at base-line levels, and the sympathoexcitatory neurons remained normally excitable by local injection of L-glutamate into the rostral medulla. In the presence of this mixed antagonist-agonist GABAergic blockade, both decreases and increases in arterial pressure elicited by excitation or inhibition of neuronal function in the caudal medulla were abolished. Similar effects were not observed after blockade of glycinergic or alpha-adrenergic receptors in the rostral ventrolateral medulla. Results suggest that the depressor neurons in the caudal ventrolateral medulla alter peripheral sympathetic vasomotor activity almost entirely by an action on GABAergic receptors in the rostral ventrolateral medulla.

Fifty-three per cent of 106 spontaneously active single neurones, located in the caudal medullary reticular formation of the urethane or halothane anaesthetized rat, were found to respond to a noxious stimulation, such as immersion of the tail in water at 52–53°C for 30 sec. The evoked responses consisted of either an increase (82%), decrease (7%) or biphasic (11%) alteration in firing rate, and could be produced by other noxious stimuli, such as a pinch, but not by stroking, tapping or joint manipulation. Morphine (0.8–1.0 mg/kg) or fentanyl (5–10 μg/kg) administered intravenously blocked the acceleration in firing rate produced by noxious stimuli, and this effect was antagonized by naloxone administered intravenously, suggesting it to be an action on specific opiate receptors. Naloxone (0.5–10 mg/kg) blocked those decreases in firing rate produced by noxious stimuli, suggesting that an endogenous opioid may be released onto these neurones as a result of noxious stimuli applied to the periphery.

After trigeminal tractotomy, neurons within the trigeminal subnucleus caudalis and adjacent subnucleus reticularis dorsalis failed to respond to mechanical stimulation of the trigeminal integument, but neurons responsive to noxious stimulation of the trigeminal region were found within subnucleus reticularis ventralis (SRV) of the caudal medulla oblongata. Neurons antidromically excited by electrical stimulation of the ipsi- or contralateral SRV were found within the reticular formation adjacent to the trigeminal subnuclei oralis and interpolaris. These neurons were also responsive to noxious stimulation of the ipsilateral trigeminal region. It was concluded that neurons relaying trigeminal nociceptive input onto SRV are located within this part of the reticular formation.

In an investigation of the origin of tonic descending inhibition of dorsal horn neurones by impulses in unmyelinated primary afferents, brainstem regions were electrolytically lesioned. With each neurone studied, tonic descending inhibition was measured before and after brainstem lesions by cooling a segment of spinal cord cephalic to the recording site. Such inhibition was not reduced by lesions of areas which, when stimulated, produce analgesia. These included the periqueductal grey and the rapheareas of the midbrain and pons-medulla. Tonic descending inhibition was reduced by bilateral lesions of the ventrolateral caudal medulla in the region of the lateral reticular nuclei. Lateral reticular areas may have a functional role in the control of pain.

S-Adenosyl-L-homocysteine (7 mg/kg), administered to PCPA-pretreated rats, was able to restore normal SWS and PS quantities, as well as circadian rhythms. This effect was at its maximum when SAH was injected 48 h after PCPA (400 mg/kg). These results are discussed in terms of post-synaptic synergetic control by SAH of serotonergic and noradrenergic nerve terminals via the periventricular system and caudal medulla in relation to environmental input.

In midcollicular decerebrate, thoracotomized, paralysed cats that were ventilated by a cycle-triggered pump and had an expiratory load, recordings were taken from expiratory neurones in the nucleus retroambigualis of the caudal medulla and from the internal intercostal nerves at T8-T9 levels. Expiratory neurone and internal intercostal activities had augmenting patterns of two types: (a) step-ramp (one-third of the neurones): a large initial increase of activity synchronous with inspiratory termination, followed by a ramp increase throughout the expiratory phase; (b) ramp (two-thirds of the neurones): a steady rise of activity without a sharp initial increase, discharge usually starting after a delay (as much as several hundred milliseconds) from the onset of expiration. Both types of unit pattern could occur together with each type of internal intercostal pattern. At the end of expiration, unit activity shut off abruptly just prior (0-120 ms) to the onset of phrenic discharge. The effects of pulmonary afferent discharge on unit and internal intercostal activities were evaluated by use of inflation tests: withholding inflation during the preceding inspiratory phase; maintaining inflation at the end-inspiratory level during expiration. Both tests produced lengthening of expiratory phase duration (TE), but their effects on activity differed. Following no-inflation during inspiration, the discharge onset delay was lengthened for most ramp neurones, but for only a minority of step-ramp neurones; the slope of activity augmentation did not change on the average; and the peak (end-expiratory) discharge frequency was only slightly increased. The predominant effect of maintained expiratory inflation was reduction of activity slope for ramp neurones and for a minority of step-ramp neurones, as well as increase of peak frequency; there was a moderate increase of discharge onset delay for ramp neurones, but not for step-ramp neurones. The lengthening of TE produced by no-inflation in the preceding inspiration was associated with lengthening of the durations of both the discharge onset delay and the discharge burst, but there was no correlation between changes of these two variables. We observed a 'reversal phenomenon': moderate inflation facilitated activity, whereas higher inflation levels depressed activity, as demonstrated by: comparison of effects of maintained expiratory deflation (removal of the expiratory load) and of maintained expiratory inflation, both of which reduced activity; comparison of effects of phasic expiratory inflations having different magnitudes.(ABSTRACT TRUNCATED AT 400 WORDS)