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G A Mihailoff

Publications and source records attributed to G A Mihailoff.

At least 19 recordsLinked to original sources

Evidence that dopamine-beta-hydroxylase immunoreactive neurons in the lateral reticular nucleus project to the spinal cord in the rat.

The existence of noradrenergic projections from the lateral reticular nucleus (LRt) to the dorsal quadrant of cervical, thoracic, or lumbar spinal cord was investigated using a combined method of WGA-apo-HRP-gold retrograde tracing and dopamine-beta-hydroxylase (DBH) immunocytochemistry. Preliminary retrograde tracing studies indicated that LRt neurons projecting to cervical, thoracic, or lumbar spinal cord were characteristically located near the perimeter of the LRt. Double-labeling experiments demonstrated that a portion of these peripherally-located, spinal-projecting neurons were DBH-immunoreactive. Double-labeled neurons were also located at the parvocellular division of the contralateral LRt in the thoracic injection cases. Double-labeled neurons were not observed at the subtrigeminal division in cervical, thoracic, or lumbar injection case. The results suggest the possibility that the noradrenergic LRt-spinal pathway might be involved in a variety of pain processing and cardiovascular regulatory functions in the rat.

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Fluorescent double-label study of lateral reticular nucleus projections to the spinal cord and periaqueductal gray in the rat.

Following injections of WGA-HRP into either the spinal cord or periaqueductal gray, labeled neurons were observed bilaterally along the periphery of the lateral reticular nucleus (LRN) magnocellular division. The possibility that some of these neurons in the LRN provide collateral axonal branches to both the periaqueductal gray and the spinal cord was investigated in rats using a retrograde double-labeling method employing two different fluorescent tracers, True Blue and Nuclear Yellow. Following sequential injection of the two fluorescent axonal tracers into the spinal cord and periaqueductal gray in the same animal, a modest number of double-labeled neurons were observed bilaterally near the medial and dorsal perimeter of the magnocellular division of the LRN. The labeled neurons were distinctly multipolar in shape and measured approximately 15-18 mu in their greatest transverse diameter. No double-labeled neurons were observed in the parvocellular or subtrigeminal divisions of the LRN. Based upon these observations, it is suggested that collaterals of the LRN-spinal pathway provide feedback information to the periaqueductal gray that might then be used to modulate the participation of the latter cell group in a variety of pain processing and cardiovascular regulatory functions.

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Hypothalamopontine projections in the rat: anterograde axonal transport studies utilizing light and electron microscopy.

Projections to the basilar pontine nuclei (BPN) from a variety of hypothalamic nuclei were traced in the rat utilizing the anterograde transport of biotinylated dextran amine. Light microscopy revealed that the lateral hypothalamic area (LH), the posterior hypothalamic area (PH), and the medial and lateral mammillary nuclei (MMN and LMN) are the four major hypothalamic nuclei that give rise to labeled fibers and terminals reaching the rostral medial and dorsomedial BPN subdivisions. Hypothalamopontine fibers extended caudally through the pontine tegmentum dorsal to the nucleus reticularis tegmenti pontis and then coursed ventrally from the main descending bundle toward the ipsilateral basilar pontine gray. Some hypothalamopontine fibers crossed the midline in the tegmental area just dorsal to the pontine gray to terminate in the contralateral BPN. Electron microscopy revealed that the ultrastructural features of synaptic boutons formed by axons arising in the LH, PH, MMN, and LMN are similar to one another. All labeled hypothalamopontine axon terminals contained round synaptic vesicles and formed asymmetric synaptic junctions with dendritic shafts as well as dendritic appendages, and occasionally with neuronal somata. Some labeled boutons formed the central axon terminal in a glomerular synaptic complex. In summary, the present findings indicate that the hypothalamus projects predominantly to the rostral medial and dorsomedial portions of the BPN which, in turn, provide input to the paraflocculus and vermis of the cerebellum. Since the hypothalamic projection zones in the BPN also receive cerebral cortical input, including limbic-related cortex, the hypothalamopontine system might serve to integrate autonomic or limbic-related functions with movement or somatic motor-related activity. Alternatively, since the cerebellum also receives direct input from the hypothalamus, the BPN may function to provide additional somatic and visceral inputs that are used by the cerebellum to perform the integrative function.

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The cerebellar-hypothalamic axis: basic circuits and clinical observations.

Experimental studies on a variety of mammals, including primates, have revealed direct and reciprocal connections between the hypothalamus and the cerebellum. Although widespread areas of the hypothalamus project to cerebellum, axons arise primarily from cells in the lateral, posterior, and dorsal hypothalamic areas; the supramammillary, tuberomammillary, and lateral mammillary nuclei; the dorsomedial and ventromedial nuclei; and the periventricular zone. Available evidence suggests that hypothalamocerebellar cortical fibers may terminate in relation to neurons in all layers of the cerebellar cortex. Cerebellohypothalamic axons arise from neurons of all four cerebellar nuclei, pass through the superior cerebellar peduncle, cross in its decussation, and enter the hypothalamus. Some axons recross the midline in caudal areas of the hypothalamus. These fibers terminate primarily in lateral, posterior, and dorsal hypothalamic areas and in the dorsomedial and paraventricular nuclei. Evidence of a cerebellar influence on the visceromotor system is presented in two patients with vascular lesions: one with a small defect in the medial cerebellar nucleus and the other with a larger area of damage involving primarily the globose and emboliform nuclei. Both patients exhibited an abnormal visceromotor response. The second, especially, showed abnormal visceromotor activity concurrent with tremor induced by voluntary movement. These experimental and clinical data suggest that the cerebellum is actively involved in the regulation of visceromotor functions.

Aged↗

Orthograde axonal transport studies of projections from the zona incerta and pretectum to the basilar pontine nuclei in the rat.

This study employed orthogradely transported axonal tracers to demonstrate, in the rat, projections that reach the basilar pontine nuclei from the zona incerta or pretectal nuclei. Except for the most rostral levels, all subdivisions of the zona incerta give rise to substantive basilar pontine projections. Although some topographic differences exist among the temination patterns of various subdivisions, no clear somatotopically organized scheme is apparent. Most incertopontine axons descend to the basilar pons in association with fibers of the medial lemniscus or crus cerebri and reach ipsilateral ventral and medial pontine gray regions. A sparse number of terminals are evident in the contralateral medial pontine gray. The anterior pretectal axons also descend with the medial lemniscus and crus cerebri to enter exclusively the ipsilateral basilar pons where they terminate most densely in ventral and medial regions. Dual orthograde labeling experiments indicate that some pretectal terminal fields in the pontine gray are shared with incertopontine projections and with afferents from the dorsal column nuclei. This potential convergence of basilar pontine afferent projections is significant in light of 1) the known somatosensory input to the zona incerta and pretectum and 2), the fractured somatotopy of peripheral cutaneous inputs that arrive in the cerebellar cortex via mossy fibers. The present studies also employed electron microscopy to identify synaptic boutons formed by incerto- and pretectopontine axons, and they proved to be remarkably similar. Each is a medium to small-sized bouton that contains spheroidal synaptic vesicles and forms asymmetric membrane specializations. Most incerto- and pretectopontine boutons participate in glomerular synaptic complexes that include a single, centrally located bouton contacted on its perimeter by several types of dendritic profiles including shafts and spine-like appendages. A relatively small number of labeled boutons of either type contacts single, isolated dendritic elements in the neuropil. Taken together, these findings suggest that some basilar pontine neurons might receive convergent inputs from the zona incerta and pretectum as well as other somatosensory-related systems such as the dorsal column nuclei and sensorimotor cortex.

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Identification of pontocerebellar axon collateral synaptic boutons in the rat cerebellar nuclei.

Injections of the orthogradely transported tracer PHA-L into the basilar pontine nuclei or reticulotegmental nucleus of hooded rats produced labeling of pontocerebellar axons that distributed to the cerebellar cortex and nuclei. EM examination of the lateral and interposed cerebellar nuclei revealed that labeled pontocerebellar axon terminals formed synaptic boutons in the cerebellar nuclei that were morphologically different from the characteristic mossy fiber terminals observed in the cerebellar cortex.

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Topographic organization of rat locus coeruleus and dorsal raphe nuclei: distribution of cells projecting to visual system structures.

Previous reports from this laboratory and elsewhere have provided evidence that the locus coeruleus (LC) and dorsal raphe (DR) nuclei are topographically organized with respect to their efferent targets. Whereas most of these previous studies have focused on relationships between these monoamine-containing brainstem nuclei and cerebral cortex, basal ganglia, and limbic structures, they have not systematically examined the distribution of LC and DR cells that project to multiple structures with common sensory or motor functions. The goal of the present study was to characterize and compare the distributions of LC and DR cells which project to different visual areas of the rat central nervous system. Long-Evans hooded rats received unilateral pressure injections of the retrograde tracer wheat germ agglutinin-horseradish peroxidase in either the dorsal lateral geniculate, ventral lateral geniculate, or lateral posterior nucleus of thalamus; superior colliculus, cortical area 17, cortical area 18a/b; cerebellar vermis (lobules VI and VII); or paraflocculus. Transverse sections through the midbrain and pons were examined by light microscopy after performing routine tetramethyl benzidine histochemical procedures. For all cases studied, retrogradely labeled cells were observed throughout the rostrocaudal extent of the LC and DR; however, labeling patterns which were distinctive for different injection sites were noted in each of these brainstem nuclei. The major conclusion drawn from this work is that subsets of LC and DR cells which project to different target structures within the rat visual system are found in overlapping but not necessarily coextensive zones within these nuclei. These studies provide further evidence of a rough topographic ordering within both the LC and DR nuclei, as well as support a new hypothesis that the outputs from each of these nuclei are organized with respect to the sensory related functions of their efferent targets.

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Cerebellar nuclear projections from the basilar pontine nuclei and nucleus reticularis tegmenti pontis as demonstrated with PHA-L tracing in the rat.

Small iontophoretic placements of the orthogradely transported axonal tracer Phaseolus vulgaris leucoagglutinin (PHA-L) were made in portions of the basilar pontine nuclei (BPN) or nucleus reticularis tegmenti pontis (NRTP) to determine if these cell groups provide projections to the cerebellar nuclei (CN) in the rat and if so, to visualize the morphology of the axons and terminals and illustrate any topographical organization in this system. Axons that originated from BPN or NRTP neurons and contained PHA-L were visualized by an immunohistochemical procedure that involved sequential incubation of tissue sections with goat anti-PHA-L antibody, biotinylated rabbit anti-goat immunoglobulin, and a biotin-avidin-peroxidase conjugate. Following injections of PHA-L restricted to ventral and medial portions of the BPN, labeled fibers were observed in the brachium pontis, the white matter dorsal to the CN, and to a lesser extent, in the white matter of the parafloccular stalk. Labeled preterminal axons entered the CN and gave rise to beaded axons that arborized primarily within dorsal portions of the lateral, interposed, and medial cerebellar nuclei. Injections of PHA-L restricted to either lateral portions of the BPN or ventrolateral regions of NRTP produced labeled fibers in the cerebellum that most frequently involved the parafloccular stalk and ventral portions of the CN. In contrast, dorsomedial NRTP injections resulted in the presence of labeled fibers both in the dorsal cerebellar white matter and the parafloccular stalk as well as dorsal and ventral portions of the CN. With the exception of the rostral and medial territory of interpositus anterior which received very sparse input, all portions of each CN subdivision seemed to exhibit some degree of terminal labeling. The density of labeled axon terminals in the CN appeared to be somewhat greater in the NRTP-injected cases compared to BPN-injected animals. These observations indicate that in the rat, both the BPN and NRTP contain neurons whose axons distribute to the CN. It is likely that most of the axons which project to the CN are collaterals of fibers that continue into the cerebellar cortex as mossy fibers but confirmation of this point must await further investigation. In light of the extensive projections from the cerebral cortex to the BPN and NRTP, this axonal system provides the cerebral cortex with a relatively direct route of access to the CN via one synapse in the BPN or NRTP.

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Glutamate immunoreactivity in the rat basilar pons: light and electron microscopy reveals labeled boutons and cells of origin of afferent projections.

Immunohistochemical methods that employed a polyclonal antiserum directed against a glutamate-hemocyanin conjugate were utilized to examine the rat basilar pontine nuclei at both light and electron microscopic levels in order to identify putative glutamatergic neural elements. A large number of cells ranging in size from 11 to 32 microns in diameter and present in all subdivisions and at all rostrocaudal levels of the basilar pons exhibited intense glutamate immunoreactivity. Immunoreactive punctate structures, confirmed by electron microscopy to be axon terminals, were homogeneously distributed throughout the pontine neuropil, although a somewhat greater accumulation was apparent medially at mid-levels of the basilar pons and laterally at more caudal levels. Immunolabeled axons were also present throughout the pontine nuclei. In order to demonstrate possible extrinsic sources of glutamate-immunoreactive axon terminals within the pontine gray, injections of wheat germ agglutinin-horseradish peroxidase were made directly into the basilar pons. Tissue was then evaluated for the presence of retrogradely transported wheat germ agglutinin-horseradish peroxidase and the same tissue sections processed for glutamate immunocytochemistry. Following this combined protocol, neuronal somata exhibiting both wheat germ agglutinin-horseradish peroxidase and glutamate immunoperoxidase reaction products were observed within layer Vb of the cerebral cortex, zona incerta, the dentate nucleus of the cerebellum, nucleus paragigantocellularis of the medullary reticular formation, and the dorsal column nuclei. Such double-labeled cells were considered to represent glutamatergic neurons that provide axonal projections to the basilar pons. Ultrastructural studies of the pontine nuclei confirmed the presence of glutamate immunogold labeling in dendrites, neuronal somata, axons, and axon terminals. Immunoreactive boutons contained round vesicles and primarily formed asymmetric synapses at various postsynaptic loci which included glutamate-immunolabeled dendritic profiles and somata. These results suggest that glutamatergic basilar pontine neurons form one segment of a multisynaptic pathway involving glutamatergic afferents to the basilar pons, glutamatergic pontocerebellar projection neurons, and the glutamatergic granule cells of the cerebellar cortex.

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Evidence for the presence of presynaptic dendrites and GABA-immunogold labeled synaptic boutons in the monkey basilar pontine nuclei.

Two general categories of GABA-immunoreactive (GABA-Ir) boutons are present in the monkey basilar pontine nuclei (BPN). One type characterized by a pale or lucent appearance is involved both in glomerular arrangements that include serial, triadic synapses, and in non-glomerular synapses. The second type of GABA-Ir bouton exhibits a wide variety in size and shape and contains a greater complement of synaptic vesicles than the first type, giving it a darker appearance in comparison to the pale GABA-Ir boutons. Such boutons participate only in non-glomerular synapses. It is suggested that the pale GABA-Ir boutons arise from the intrinsic population of GABA neurons, while the darker appearing boutons might take origin from one of the GABA-ergic afferent systems that reach the BPN.

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GABAergic neural elements in the rat basilar pons: electron microscopic immunochemistry.

Previous light microscopic immunoperoxidase studies of glutamic acid decarboxylase (GAD)-immunoreactive neural elements in the rat basilar pontine nuclei revealed immunocytochemical reaction product in neuronal somata and axon terminals. In the present study, pre-embedding immunoperoxidase labeling of GAD or gamma-aminobutyric acid (GABA) and postembedding immunogold labeling of GABA allowed the ultrastructural visualization of these neural elements in the basilar pontine nuclei of colchicine-treated animals. At the electron microscopic level, immunolabeled neuronal somata exhibited smoothly contoured nuclei, whereas some dendrites also contained reaction product after immunocytochemical treatment and were postsynaptic to both immunoreactive and nonimmunoreactive axon terminals. Synaptic boutons immunoreactive for GAD or GABA exhibited cross-sectional areas that ranged from 0.1 to 3.8 microns 2 and generally appeared round or elongated in most sections. The majority (95%) of immunolabeled boutons contained pleomorphic synaptic vesicles and formed symmetric synapses at their postsynaptic loci; however, boutons exhibiting round vesicles and boutons forming asymmetric synapses (5%) were also immunopositive. Small (less than 1.5 microns 2) GAD- or GABA-labeled axon terminals formed synaptic contact mainly with small dendritic profiles, dendritic spines, and neuronal somata, whereas large labeled boutons (greater than 1.5 microns 2) formed synapses with all sizes of dendritic profiles. Occasionally, a single immunolabeled bouton formed synaptic contact with two separate postsynaptic dendrites. It is suggested that the immunolabeled neuronal somata and dendrites observed in the rat basilar pontine nuclei represent a population of pontine local circuit neurons; however, it is known that GABAergic cell groups extrinsic to the pontine gray provide afferent projections to the basilar pons, and therefore at least some immunoreactive axon terminals present in the pontine nuclei are derived from these extrinsic sources. The ultrastructural observation of GABAergic neural elements in the rat basilar pontine nuclei confirms previous light microscopic findings and provides an anatomical substrate through which GABAergic neurons, whether arising from an intrinsic or extrinsic source, might exert an inhibitory influence on target cells within the pontine nuclei.

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Convergence of cortical and cerebellar projections on single basilar pontine neurons: a light and electron microscopic study in the rat.

A protocol that involved a combination of two orthogradely transported tracer substances, wheat agglutinin-horseradish peroxidase and Phaseolus vulgaris leucoagglutinin injected at separate locations in the same animal was utilized to investigate the possible congruence of axonal projection fields formed by the cerebral cortical and cerebellar afferents to the basilar pontine nuclei. When large placements of tracer material were made in the cerebellar nuclei to label the cerebellopontine projections and a second tracer was injected in one of several cerebral cortical areas to visualize certain corticopontine projections, it was noted that axon terminal zones of the cortical and cerebellar systems occupied greater or lesser amounts of the same basilar pontine territory depending on the location of the cerebral cortical injection. Cerebellopontine terminal fields exhibited their greatest congruency with projections from the motor cortex containing the representation for facial musculature and with projections from the forelimb sensorimotor cortex. A lesser degree of overlap was observed when cerebellar projection zones were visualized in combination with basilar pontine projections from sensory face cortex, hindlimb sensorimotor cortex, visual cortex and auditory cortex. In addition, it was apparent that portions of the cerebellopontine and corticopontine terminal fields did not overlap at all. A related series of electron microscopic experiments was undertaken to establish that within the zones of overlapping cerebellar and cortical projections, there was in fact a convergence of the two afferent systems on single basilar pontine neurons. Boutons of the corticopontine system were labeled by the orthograde transport of wheat germ agglutinin horseradish peroxidase injected into the sensorimotor cortex while cerebellopontine terminals were marked for electron microscopic identification in the same animal by transecting the brachium conjunctivum and allowing sufficient time for boutons in the pontine nuclei to exhibit degeneration. Although the number of definitive examples of convergence was small, nonetheless it was possible to observe single basilar pontine neuron dendrites receiving synaptic contacts from both the cortical and cerebellar afferents systems. Taken together these observations indicate that some basilar pontine neurons receive a dual or convergent input from the cerebral cortex and cerebellar nuclei. It is difficult to estimate the prevalence of such convergence since cortical and cerebellar inputs typically contact distal and proximal pontine neuron dendrites, respectively, thus limiting the chances that both types of boutons can be observed in contact with a single basilar pontine neuron dendrite.(ABSTRACT TRUNCATED AT 400 WORDS)

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Survey of noncortical afferent projections to the basilar pontine nuclei: a retrograde tracing study in the rat.

The retrograde transport of the conjugate wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was used in the rat to identify the cell bodies of origin for all subcortical projections to the basilar pontine nuclei (BPN). A parapharyngeal surgical approach was used to allow the injection micropipette to enter the BPN from the ventral aspect of the brainstem and thus avoid any potential for false-positive labeling due to transection and injury-filling of axonal systems located dorsal to the basilar pontine gray. A surprisingly large number of BPN afferent cell groups were identified in the present study. Included were labeled somata in the lumbar spinal cord and a large variety of nuclei in the medulla, pons, and midbrain, as well as labeled cells in diencephalic and telencephalic nuclei such as the zona incerta, ventral lateral geniculate, hypothalamus, amygdala, nucleus basalis of Meynert, and the horizontal nucleus of the diagonal band of Broca. Quite a number of cell groups known to project directly to the cerebellum also exhibited labeled somata in the present study. To explore the possibility that such neurons were labeled because their axons were transected and injury-filled as they coursed through the BPN injection site to enter the cerebellum via the brachium pontis, a series of rats received complete, bilateral lesions of the brachium pontis followed 30-60 minutes later with multiple, diffuse injections of WGA-HRP (12-16 placements per animal) throughout the cerebellar cortex. In another series of animals, the massive cerebellar WGA-HRP injections were not preceded by brachium pontis lesions. In the latter cases, each of the cell groups in question that were known to project directly to the cerebellum exhibited labeled somata. However, when the cerebellar HRP injections were preceded by brachium pontis lesions, each of the cell groups in question continued to exhibit labeled somata in numbers comparable to that observed in the nonlesion cases. This implies that such neurons project to the BPN and the cerebellar cortex and that the axons of these particular neurons do not project to the cerebellum via the brachium pontis.

Afferent Pathways↗

Collateral branches of cerebellopontine axons reach the thalamus, superior colliculus, or inferior olive: a double-fluorescence and combined fluorescence-horseradish peroxidase study in the rat.

Retrograde double-labeling methods that used two different fluorescent dyes or a fluorescent dye in combination with wheat germ agglutinin horseradish peroxidase were used in the rat to study the collateralization of cerebellopontine fibers to the thalamus, the superior colliculus, or the inferior olive. In cases with combined basilar pontine nuclei and thalamus injections, double-labeled neurons were located in the rostral part of the lateral cerebellar nucleus as well as within the interpositus anterior and interpositus posterior nuclei. These cells are medium to large in size and multipolar-shaped. A much smaller number of double-labeled cells was observed in the combined basilar pontine nuclei and superior colliculus injections. In these cases most of the double-labeled cells were intermediate- to large-sized and either bipolar- or multipolar-shaped. Such neurons were distributed throughout the rostrocaudal extent of the lateral cerebellar nucleus, with only a few double-labeled cells located in the interpositus anterior and posterior nuclei. Finally, in the cases with combined basilar pontine nuclei and inferior olive injections, double-labeled cells were located in interpositus anterior and posterior nuclei and the medial portion of the lateral cerebellar nucleus. The double-labeled cells were relatively small in size and most were spindle-shaped. No double-labeled cells were observed in the medial cerebellar nucleus in any of the three injection combinations. Based upon the observation of double-labeled neurons in the deep cerebellar nuclei in each of the three injection combinations involving the basilar pontine nuclei, we conclude that cerebellar projections to the basilar pons arise in part as collaterals of axons that project to the thalamus, superior colliculus, or the inferior olive.

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A double retrograde fluorescent tracing analysis of dorsal column nuclear projections to the basilar pontine nuclei, thalamus, and superior colliculus in the rat.

Injections of the fluorescent dyes Nuclear yellow and True blue were used to determine that the dorsal column nuclei project in collateral fashion to the basilar pontine nuclei (BPN) and the ventral posterolateral nucleus of the thalamus or the BPN and the superior colliculus. Results indicated that relatively few dorsal column nuclear cells project to both the basilar pons and the superior colliculus. In contrast, many dorsal column nuclear cells that project to the BPN also give rise to collateral projections to the thalamus. Thus it is suggested that the latter dorsal column-BPN connections might at least represent in part the anatomical substrate for the electrophysiological demonstration that cerebellar granule cells can be activated at relatively short latency by peripheral tactile receptor stimulation.

Afferent Pathways↗

A review of recent observations concerning the synaptic organization of the basilar pontine nuclei.

Ultrastructural studies are described that have identified in the basilar pontine nuclei (BPN), the synaptic boutons formed by the corticopontine, cerebellopontine, tectopontine, and dorsal column nuclei-pontine afferent projection systems. In addition, immunocytochemical studies visualized neuronal somata, dendrites, and synaptic boutons that contain immunoreactivity for GABA or the synthesizing enzyme glutamic acid decarboxylase (GAD). Based upon differences in the mode of degeneration and postsynaptic locus of degenerative synaptic boutons in the BPN, it is suggested that two types of cortical neurons and three classes of deep cerebellar nuclear cells project to the BPN. For similar reasons, it appears that two types of neurons in the dorsal column nuclei project to the BPN while only one type of afferent synaptic bouton takes origin from the superior colliculus. Furthermore it appears that the population of BPN neurons projecting to the paramedian lobule receives convergent inputs from the cutaneous periphery and the corresponding region of sensorimotor cortex. Studies employing GAD immunohistochemistry indicate that GABA-ergic neurons and axon terminals are present in the BPN and thus support the suggestion that a local inhibitory interneuron is present within the BPN. Taken together these observations suggest that basilar pontine neurons might play a more active role in the integration of various types of information destined for the cerebellar cortex than has previously been recognized.

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Convergence of cortico- and cuneopontine projections onto components of the pontocerebellar system in the rat: an anatomical and electrophysiological study.

Previous studies in the rat have demonstrated that corresponding peripheral tactile and somatosensory cortical inputs converge within the granule cell layer of various cerebellar lobules and further that descending corticopontine projections from the forelimb sensory cortex (FLSCx) partially overlap with the projection zones of ascending basilar pontine afferents from nucleus cuneatus (NC). The present study employed anatomical and electrophysiological procedures to determine whether cortical and dorsal column nuclear afferent projections converge on pontine neurons that, in turn, provide mossy fiber input to the granule cell layer of the paramedian lobule (PML), i.e., that portion of the rodent cerebellum shown to receive forelimb peripheral inputs. The combination of the orthograde and retrograde axonal transport of horseradish peroxidase (HRP) conjugated to wheat germ agglutinin (WGA) was used light microscopically to demonstrate that orthogradely labeled projections from injections of the FLSCx and NC converged with ponto-paramedian projection neurons that were retrogradely labeled from injections of the PML. These studies were also repeated in conjunction with ablations of either the FLSCx or NC which resulted in the ultrastructural identification of degenerating, as well as WGA-HRP labeled axonal boutons of these pontine afferent projections thus confirming that such projections actually formed synaptic contacts with the retrogradely labeled pontoparamedian projection neurons. Single unit recording analyses of neurons in the ventromedial region of the basilar pons following combined electrical stimulation of various regions of the sensorimotor cortex and the contralateral body surface indicated that approximately 40% of all cells recorded responded to electrical stimulation of corresponding regions of the cortex and periphery, particularly the FLSCx and the forepaw. Natural cutaneous stimuli applied to the forepaw that also elicited responses in these same groups of basilar pontine neurons and were associated with relatively small receptive fields. Taken together, these observations indicate that the previously observed convergence of peripheral and somatosensory cortical inputs within the granule cell layer of the cerebellar cortex may be at least partially organized at the level of the basilar pons.

Action Potentials↗