Revealing the cerebello-ponto-hypothalamic pathway in the human brain.

The cerebellum is shown to be involved in some limbic functions of the human brain such as emotion and affect. The major connection of the cerebellum with the limbic system is known to be through the cerebello-hypothalamic pathways. The consensus is that the projections from the cerebellar nuclei to the limbic system, and particularly the hypothalamus, or from the hypothalamus to the cerebellar nuclei, are through multisynaptic pathways in the bulbar reticular formation. The detailed anatomy of the pathways responsible for mediating these responses, however, is yet to be determined. Diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of the cerebello-ponto-hypothalamic (CPH) pathway. This study aimed to investigate the utility of high-spatial-resolution diffusion tensor tractography for mapping the trajectory of the CPH tract in the human brain. Fifteen healthy adults were studied. We delineated, for the first time, the detailed trajectory of the CPH tract of the human brain in fifteen normal adult subjects using high-spatial-resolution diffusion tensor tractography. We further revealed the close relationship of the CPH tract with the optic tract, temporo-pontine tract, amygdalofugal tract and the fornix in the human brain.

Terminal field specificity of forebrain efferent axons to the pontine parabrachial nucleus and medullary reticular formation.

The pontine parabrachial nucleus (PBN) and medullary reticular formation (RF) are hindbrain regions that, respectively, process sensory input and coordinate motor output related to ingestive behavior. Neural processing in each hindbrain site is subject to modulation originating from several forebrain structures including the insular gustatory cortex (IC), bed nucleus of the stria terminalis (BNST), central nucleus of the amygdala (CeA), and lateral hypothalamus (LH). The present study combined electrophysiology and retrograde tracing techniques to determine the extent of overlap between neurons within the IC, BNST, CeA and LH that target both the PBN and RF. One fluorescent retrograde tracer, red (RFB) or green (GFB) latex microbeads, was injected into the gustatory PBN under electrophysiological guidance and a different retrograde tracer, GFB or fluorogold (FG), into the ipsilateral RF using the location of gustatory NST as a point of reference. Brain tissue containing each forebrain region was sectioned, scanned using a confocal microscope, and scored for the number of single and double labeled neurons. Neurons innervating the RF only, the PBN only, or both the medullary RF and PBN were observed, largely intermingled, in each forebrain region. The CeA contained the largest number of cells retrogradely labeled after tracer injection into either hindbrain region. For each forebrain area except the IC, the origin of descending input to the RF and PBN was almost entirely ipsilateral. Axons from a small percentage of hindbrain projecting forebrain neurons targeted both the PBN and RF. Target specific and non-specific inputs from a variety of forebrain nuclei to the hindbrain likely reflect functional specialization in the control of ingestive behaviors.

The fate of spontaneous synchronous rhythms on the cerebrocerebellar loop.

How does the cerebellum participate in neocortical rhythms? Neocortical signals destined for the cerebellum are integrated in the pontine nuclei (PN) with cerebellar output signals via a direct, reciprocal feedback loop with the cerebellar nuclei (CN). The present study investigated the fate of two spontaneously occurring rhythms in rat neocortex under ketamine anesthesia-slow wave activity at around 1 Hz and gamma oscillations-within this pontonuclear feedback loop. Coordinated oscillatory neuronal activity was studied using simultaneous multineuron recordings in primary motor cortex (M1), PN, and lateral CN. It was revealed that slow burst firing-known in neocortex as "up and down states"-is readily conveyed within the pontonuclear feedback loop and thus engages the entire cerebropontocerebellothalamic loop. In contrast, gamma band synchronous oscillations reached only the PN under the present experimental conditions. Surprisingly, many CN single units were actually found to oscillate in the gamma range, but they completely failed to synchronize with other units in either CN or PN. These results show firstly that slow concerted activity can readily engage the entire cerebrocerebellar loop. Secondly, they raise the possibility that fast gamma oscillations may be incompatible with cerebellar processing and get blocked out. Future studies in behaving animals are needed to answer the question whether signals coded in gamma band frequency are converted to another carrier code using the feedback control exerted by the pontonuclear loop.

Positron emission tomography correlates of visually-scored electroencephalographic waveforms during non-Rapid Eye Movement sleep.

Visually-scored, non-Rapid Eye Movement (REM) sleep electroencephalographic (EEG) waveform activity for each 30-s sleep scored epoch-including the number of sleep spindles, the number of K-complexes, and the percentage of delta waves occupying the epoch-was correlated with H(2)(15)O positron emission tomography. Sleep spindle correlations included positive correlations in the thalamus and right hippocampus. K-complex correlations included positive correlations in the frontomedian prefrontal cortex and cerebellum. Delta wave correlations included negative correlations in the thalamus, frontomedian prefrontal cortex, dorsal pons, and primary visual cortex. Each pattern of correlations may suggest a functional significance for these waveforms that relates to a waking outcome.

MCHergic projections to the nucleus pontis oralis participate in the control of active (REM) sleep.

Neurons that utilize melanin-concentrating hormone (MCH) as a neuromodulator are located in the lateral hypothalamus and incerto-hypothalamic area and project diffusely throughout the central nervous system, including areas that participate in the generation and maintenance of sleep and wakefulness. Recent studies have shown that hypothalamic MCHergic neurons are active during active sleep (AS), and that intraventricular microinjections of MCH induce AS sleep; however, there are no data available regarding the manner in which MCHergic neurons participate in the control of this behavioral state. Utilizing immunohistochemical and retrograde tracing techniques, we examined, in the cat, projections from MCHergic neurons to the nucleus pontis oralis (NPO), which is considered to be the executive area that is responsible for the generation and maintenance of AS. In addition, we explored the effects on sleep and waking states produced by the microinjection of MCH into the NPO. We first determined that MCHergic fibers and terminals are present in the NPO. We also found that when a retrograde tracer (cholera toxin subunit B) was placed in the NPO MCHergic neurons of the hypothalamus were labeled. When MCH was microinjected into the NPO, there was a significant increase in the amount of AS (19.8+/-1.4% versus 11.9+/-0.2%, P<0.05) and a significant decrease in the latency to AS (10.4+/-4.2 versus 26.6+/-2.3 min, P<0.05). The preceding anatomical and functional data support our hypothesis that the MCHergic system participates in the regulation of AS by modulating neuronal activity in the NPO.

The middle perforated substance of the diencephalon.

The diencephalon, upper brain stem and other basal brain structures are supplied chiefly by penetrating branches of the cerebral arteries. We examined the retrochiasmatic space between the superior border of the pons and posterior edge of the optic chiasm in six randomly selected adult fresh brain specimens. Lateral or anterolateral to the mamillary bodies, two small quadrangular spaces (2.5 x 3.5 mm) were found that were limited laterally by the junction of the optic tract and crus cerebri. These spaces were pierced on each side by 1 to 5 small penetrating branches (premamillary arterial complex) of the posterior communicating artery. A single, large and obliquely oriented penetrating branch of the posterior communicating artery (the so-called premamillary, thalamotuberal or mamillothalamic artery) was found to pierce this area in all specimens. Based on our findings, the above-mentioned vessels of this perforating substance supply the floor of third ventricle, hypothalamus and ventral thalamic nuclei. Hence, special attentions should be made during surgery in this area such as third ventriculostomy for hydrocephalus.

The medial nucleus of the trapezoid body in rat: spectral and temporal properties vary with anatomical location of the units.

The medial nucleus of the trapezoid body (MNTB) is a distinct nucleus in the superior olivary complex that transforms excitatory input from the cochlear nucleus into a widespread inhibitory output to distinct auditory brainstem nuclei. Few studies have dealt with the response properties of MNTB neurons to sound stimulation using in vivo preparations. In order to have a better understanding of the functional significance of the MNTB in auditory processing we report the basic temporal and spectral response properties of its principal cells using single-unit extracellular recordings to acoustic stimulation with pure tones and amplitude-modulated stimuli in the rat. Ninety-seven per cent of units showed V-shaped frequency response areas. Rate level functions were mainly saturating (51%) or monotonic (45%) at high intensities. Post-stimulus time histograms typically were characterised as primary-like with notch (59%) or primary-like (33%). Units showed good phase-locking to sinusoidally amplitude-modulated signals with vector strength VS values up to 0.87. Modulation transfer functions had low-pass shapes at near-threshold levels, with cut-off frequencies ranging from 370 to 1270 Hz. Exploration of the relationship between the temporal and spectral properties and the location of the units in the MNTB yielded characteristic frequency (CF)-dependent response properties (latency, Q(10) and cut-off frequency) following a medio-lateral gradient, and CF-independent response features (maximum firing rate) following a dorso-ventral gradient.

GABAergic and non-GABAergic thalamic, hypothalamic and basal forebrain projections to the ventral oral pontine reticular nucleus: their implication in REM sleep modulation.

The ventral part of the oral pontine reticular nucleus (vRPO) is a demonstrated site of brainstem REM-sleep generation and maintenance. The vRPO has reciprocal connections with structures that control other states of the sleep-wakefulness cycle, many situated in the basal forebrain and the diencephalon. Some of these connections utilize the inhibitory neurotransmitter GABA. The aim of the present work is to map the local origin of the basal forebrain and diencephalon projections to the vRPO whether GABAergic or non-GABAergic. A double-labelling technique combining vRPO injections of the neuronal tracer, cholera-toxin (CTB), with GAD-immunohistochemistry, was used for this purpose in adult cats. All of the numerous CTB-positive neurons in the reticular thalamic and dorsocaudal hypothalamic nuclei were double-labelled (CTB/GAD-positive) neurons. Approximately 15%, 14% and 16% of the CTB-positive neurons in the zona incerta and the dorsal and lateral hypothalamic areas are, respectively, CTB/GAD-positive neurons. However, only some double-labelled neurons were found in other hypothalamic nuclei with abundant CTB-positive neurons, such as the paraventricular nucleus, perifornical area and H1 Forel field. In addition, CTB-positive neurons were abundant in the central amygdaline nucleus, terminal stria bed nuclei, median preoptic nucleus, medial and lateral preoptic areas, dorsomedial and ventromedial hypothalamic nuclei, posterior hypothalamic area and periventricular thalamic nucleus. The GABAergic and non-GABAergic connections described here may be the morphological pillar through which these prosencephalic structures modulate, either by inhibiting or by exciting, the vRPO REM-sleep inducing neurons during the different sleep-wakefulness cycle states.

Neuroanatomical mapping of juvenile rat brain regions with prominent basal signal in [(35)S]GTPgammaS autoradiography.

[(35)S]GTPgammaS autoradiography represents a powerful functional approach to detect receptor-dependent G(i/o) protein activity in anatomically defined brain structures. Inherent to this technique, however, is the notable basal signal evident in several brain regions in the absence of receptor stimulation by exogenously added agonist. In the rat brain, much of this basal labelling derives from tonic activation of adenosine A(1) and lysophosphatidic acid LPA(1) receptors in the gray and white matter regions, respectively. Despite the elimination of the two receptor activities, prominent basal [(35)S]GTPgammaS labelling is still evident in discrete brain structures, possibly reflecting regional enrichment of G(i/o) and/or constitutive receptor activity or the presence of still unknown endogenous ligands activating their orphan receptors. Here, the anatomical distribution of the enhanced basal signal was systematically mapped in brain sections of 4-week-old male Wistar rats. Regions with prominent basal [(35)S]GTPgammaS labelling represented neuroanatomically distinct structures, in particular various thalamic and hypothalamic nuclei. For instance, the paraventricular thalamic nucleus, the bed nucleus of the stria terminalis and the subfornical organ were highly labelled, as were the periaqueductal gray and the nucleus of the solitary tract. Pre-treatment with N-ethylmaleimide (NEM), an alkylating agent preventing all known receptor-driven G protein activity in cryostat sections markedly decreased the basal binding in all examined regions. In preliminary screening, selective antagonists for various brain-enriched G(i/o)-coupled receptors failed to suppress the basal signal in any of the studied regions.

Standardizing display conditions of diffusion-weighted images using concurrent b0 images: a multi-vendor multi-institutional study.

PURPOSE: To establish a practical method that uses concurrent b0 images to standardize the display conditions for diffusion-weighted images (DWI) that vary among institutions and interpreters. METHOD: Using identical parameters, we obtained DWI for 12 healthy volunteers at 4 institutions using 4 MRI scanners from 3 vendors. Three operators manually set the window width for the images equal to the signal intensity of the normal-appearing thalamus on b0 images and set the window level at half and then exported the images to 8-bit gray-scale images. We calculated the mean pixel values of the brain objects in the images and examined the variation among scanners, operators, and subjects. RESULT: Following our method, the DWI of the 12 subjects obtained using the 4 different scanners had nearly identical contrast and brightness. The mean pixel values of the brain on the exported images among the operators and subjects were not significantly different, but we found a slight, significant difference among the scanners. CONCLUSION: Determining DWI display conditions by using b0 images is a simple and practical method to standardize window width and level for evaluating diffusion abnormalities and decreasing variation among institutions and operators.

Strategies for improving the detection of fMRI activation in trigeminal pathways with cardiac gating.

Functional magnetic resonance imaging (fMRI) has become a powerful tool for studying the normal and diseased human brain. The application of fMRI in detecting neuronal signals in the trigeminal system, however, has been hindered by low detection sensitivity due to activation artifacts caused by cardiac pulse-induced brain and brainstem movement. A variety of cardiac gating techniques have been proposed to overcome this issue, typically by phase locking the sampling to a particular time point during each cardiac cycle. We sought to compare different cardiac gating strategies for trigeminal system fMRI. In the present study, we used tactile stimuli to elicit brainstem and thalamus activation and compared the fMRI results obtained without cardiac gating and with three different cardiac gating strategies: single-echo with TR of 3 or 9 heartbeats (HBs) and dual-echo T2*-mapping EPI (TR = 2 HBs, TE = 21/55 ms). The dual-echo T2* mapping and the single-echo with TR of 2 and 3 HBs cardiac-gated fMRI techniques both increased detection rate of fMRI activation in brainstem. Activation in the brainstem and the thalamus was best detected by cardiac-gated dual-echo EPI.

Three-dimensional topography of corticopontine projections from rat sensorimotor cortex: comparisons with corticostriatal projections reveal diverse integrative organization.

The major cortical-subcortical re-entrant pathways through the basal ganglia and cerebellum are considered to represent anatomically segregated channels for information originating in different cortical areas. A capacity for integrating unique combinations of cortical inputs has been well documented in the basal ganglia circuits but is largely undefined in the precerebellar circuits. To compare and quantify the amount of overlap that occurs in the first link of the cortico-ponto-cerebellar pathway, a dual tracing approach was used to map the spatial relationship between projections originating from the primary somatosensory cortex (SI), the secondary somatosensory cortex (SII), and the primary motor cortex (MI). The anterograde tracers biotinylated dextran amine and Fluoro-Ruby were injected into homologous whisker representations of either SI and SII, or SI and MI. The ensuing pontine labeling patterns were analyzed using a computerized three-dimensional reconstruction approach. The results demonstrate that whisker-related projections from SI and MI are largely segregated. At some locations, the two projections are adjoining and partly overlapping. Furthermore, SI contributes significantly more corticopontine projections than MI. By comparison, projections from corresponding representations in SI and SII terminate in similar parts of the pontine nuclei and display considerable amounts of spatial overlap. Finally, comparison of corticopontine and corticostriatal projections in the same experimental animals reveals that SI-SII overlap is significantly larger in the pontine nuclei than in the neostriatum. These structural differences indicate a larger capacity for integration of information within the same sensory modality in the pontocerebellar system compared to the basal ganglia.

Effects of age and sex on volumes of the thalamus, pons, and cortex.

Volumes of thalamus, pons, cortical gray matter, and white matter were derived from MR brain images of healthy men and women spanning the adult age range in order to delineate patterns of aging and to compare age and sex effects in thalamus and pons with such effects in cortical gray and white matter volumes. Men had larger intracranial volume (ICV) than women, but ICV did not correlate with age in either sex. Thalamic, pontine, and cortical white matter volumes did not differ between men and women once ICV differences were taken into account, but men had more cortical gray matter than women even after accounting for ICV. Volumes of pons and thalamus were associated, independent of ICV, in women but not in men. Thalamic volume declined linearly with age at a similar rate in both men and women, whereas cortical gray matter volume declined more steeply with age in men than women. Both pontine and cortical white matter volumes remained stable across the age span in both men and women.

Effects of alcohol dependence comorbidity and antipsychotic medication on volumes of the thalamus and pons in schizophrenia.

OBJECTIVE: Postmortem and in vivo brain imaging studies have identified abnormalities in the thalamus and the pons in both schizophrenia and alcoholism. The authors sought to determine whether patients with both schizophrenia and alcohol dependence would manifest exaggerated volume deficits in either structure. METHOD: Volumetric measures of the left and right thalamus and the pons were derived from magnetic resonance imaging scans obtained from 27 patients with schizophrenia, 19 patients with schizophrenia and comorbid alcohol dependence, 25 patients with alcohol dependence without comorbid axis I disorders, and 51 healthy comparison subjects. RESULTS: The alcohol-dependent patients had significant volume deficits in both the thalamus and the pons. Among patients with schizophrenia, there were no differences in thalamus volumes between those with and without comorbid alcohol dependence. However, patients with schizophrenia who were taking atypical antipsychotic medications had bilateral thalamic deficits, whereas those taking typical neuroleptics did not. Patients with schizophrenia and comorbid alcohol dependence had deficits in the pons. CONCLUSIONS: Patients with schizophrenia and comorbid alcohol dependence are at risk for alcohol-related reduction of pontine structures that are not necessarily affected by schizophrenia per se. The effect of alcohol dependence on the thalamus in schizophrenic patients may be mitigated by the type of neuroleptic medication they receive.

The evolution of the cortico-cerebellar complex in primates: anatomical connections predict patterns of correlated evolution.

Investigations into the evolution of the primate brain have tended to neglect the role of connectivity in determining which brain structures have changed in size, focusing instead on changes in the size of the whole brain or of individual brain structures, such as the neocortex, in isolation. We show that the primate cerebellum, neocortex, vestibular nuclei and relays between them exhibit correlated volumetric evolution, even after removing the effects of change in other structures. The patterns of correlated evolution among individual nuclei correspond to their known patterns of connectivity. These results support the idea that the brain evolved by mosaic size change in arrays of functionally connected structures. Furthermore, they suggest that the much discussed expansion of the primate neocortex should be re-evaluated in the light of conjoint cerebellar expansion.

Cortical innervation of the facial nucleus in the non-human primate: a new interpretation of the effects of stroke and related subtotal brain trauma on the muscles of facial expression.

The corticobulbar projection to musculotopically defined subsectors of the facial nucleus was studied from the face representation of the primary (M1), supplementary (M2), rostral cingulate (M3), caudal cingulate (M4) and ventral lateral pre- (LPMCv) motor cortices in the rhesus monkey. We also investigated the corticofacial projection from the face/arm transitional region of the dorsal lateral premotor cortex (LPMCd). The corticobulbar projection was defined by injecting anterograde tracers into the face representation of each motor cortex. In the same animals, the musculotopic organization of the facial nucleus was defined by injecting fluorescent retrograde tracers into individual muscles of the upper and lower face. The facial nucleus received input from all face representations. M1 and LPMCv gave rise to the heaviest projection with progressively diminished intensity occurring in the M2, M3, M4 and LPMCd projections, respectively. Injections in all cortical face representations labelled terminals in all nuclear subdivisions (dorsal, intermediate, medial and lateral). However, significant differences occurred in the proportion of labelled boutons found within each functionally characterized subdivision. M1, LPMCv, LPMCd and M4 projected primarily to the contralateral lateral subnucleus, which innervated the perioral musculature. M2 projected bilaterally to the medial subnucleus, which supplied the auricular musculature. M3 projected bilaterally to the dorsal and intermediate subnuclei, which innervated the frontalis and orbicularis oculi muscles, respectively. Our results indicate that the various cortical face representations may mediate different elements of facial expression. Corticofacial afferents from M1, M4, LPMCv and LPMCd innervate primarily the contralateral lower facial muscles. Bilateral innervation of the upper face is supplied by M2 and M3. The widespread origin of these projections indicates selective vulnerability of corticofacial control following subtotal brain injury. The finding that all face representations innervate all nuclear subdivisions, to some degree, suggests that each motor area may participate in motor recovery in the event that one or more of these motor areas are spared following subtotal brain injury. Finally, the fact that a component of the corticofacial projection innervating both upper and lower facial musculature arises from the limbic proisocortices (M3 and M4) and frontal isocortices (M1, M2, LPMCv and LPMCd) suggests a potential anatomical substrate that may contribute to the clinical dissociation of emotional and volitional facial movement.

Ascending projections from the area around the spinal cord central canal: A Phaseolus vulgaris leucoagglutinin study in rats.

A single small iontophoretic injection of Phaseolus vulgaris leucoagglutinin labels projections from the area surrounding the spinal cord central canal at midthoracic (T6-T9) or lumbosacral (L6-S1) segments of the spinal cord. The projections from the midthoracic or lumbosacral level of the medial spinal cord are found: 1) ascending ipsilaterally in the dorsal column near the dorsal intermediate septum or the midline of the gracile fasciculus, respectively; 2) terminating primarily in the dorsal, lateral rim of the gracile nucleus and the medial rim of the cuneate nucleus or the dorsomedial rim of the gracile nucleus, respectively; and 3) ascending bilaterally with slight contralateral predominance in the ventrolateral quadrant of the spinal cord and terminating in the ventral and medial medullary reticular formation. Other less dense projections are to the pons, midbrain, thalamus, hypothalamus, and other forebrain structures. Projections arising from the lumbosacral level are also found in Barrington's nucleus. The results of the present study support previous retrograde tract tracing and physiological studies from our group demonstrating that the neurons in the area adjacent to the central canal of the midthoracic or lumbosacral level of the spinal cord send long ascending projections to the dorsal column nucleus that are important in the transmission of second-order afferent information for visceral nociception. Thus, the axonal projections through both the dorsal and the ventrolateral white matter from the CC region terminate in many regions of the brain providing spinal input for sensory integration, autonomic regulation, motor and emotional responses, and limbic activation.

Characterization of the extent of pontomesencephalic cholinergic neurons' projections to the thalamus: comparison with projections to midbrain dopaminergic groups.

We sought to determine whether pontomesencephalic cholinergic neurons which we have been shown previously to project to the substantia nigra and ventral tegmental area also contribute to the thalamic activation projection from the pedunculopontine and laterodorsal tegmental nuclei. Retrograde tracing, immunohistochemical localization of choline acetyltransferase and statistical methods were used to determine the full extent of the cholinergic projection from the pedunculopontine and laterodorsal tegmental nuclei to the thalamus. Progressively larger Fluoro-Gold injections in to the thalamus proportionally labeled increasing numbers of pontomesencephalic cholinergic cells both ipsi- and contralaterally in the pedunculopontine and laterodorsal tegmental nuclei. Multiple large thalamic injections left only a small fraction of the ipsilateral pontomesencephalic cholinergic group unlabeled. This small remainder did not correspond to the populations which project to the substantia nigra and ventral tegmental area, thereby indicating that substantia nigra- and ventral tegmental area-projecting cholinergic neurons must also project to the thalamus. We examined whether there existed any set of cholinergic neurons in the pedunculopontine and laterodorsal tegmental nuclei which did not innervate a thalamic target. The distribution of descending projections of the pedunculopontine and laterodorsal tegmental nuclei demonstrated that the unlabeled remainder cannot correspond to a purely descending group. We also show that substance P-positive cholinergic cells in the laterodorsal tegmental nucleus project to the thalamus. Further studies demonstrated that the small population of cholinergic cells left unlabeled from the thalamus were the smallest sized cholinergic cells, and included two groups of small, light-staining cholinergic cells located in the parabrachial area and central gray, adjacent to the main pedunculopontine and laterodorsal tegmental nuclei cholinergic groups. These small cells, in contrast to thalamic-projecting cholinergic cells, did not stain positively for reduced nicotinamide adenine dinucleotide phosphate-diaphorase. Taken together, these results indicated that all of the reduced nicotinamide adenine dinucleotide phosphate diaphorase-positive/choline acetyltransferase-positive neurons of the pedunculopontine/laterodorsal tegmental nuclei ascend to innervate some portion of the thalamus, in addition to the other targets they innervate. These findings indicate that the diverse physiological and behavioral effects attributed to the activity of pontomesencephalic cholinergic neurons should not be dissociated from their activating effects in the thalamus.

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.

Anatomy and physiology of principal cells of the medial nucleus of the trapezoid body (MNTB) of the cat.

We have recorded from principal cells of the medial nucleus of the trapezoid body (MNTB) in the cat's superior olivary complex using either glass micropipettes filled with Neurobiotin or horseradish peroxidase for intracellular recording and subsequent labeling or extracellular metal microelectrodes relying on prepotentials and electrode location. Labeled principal cells had cell bodies that usually gave rise to one or two primary dendrites, which branched profusely in the vicinity of the cell. At the electron microscopic (EM) level, there was a dense synaptic terminal distribution on the cell body and proximal dendrites. Up to half the measured cell surface could be covered with excitatory terminals, whereas inhibitory terminals consistently covered about one-fifth. The distal dendrites were very sparsely innervated. The thick myelinated axon originated from the cell body and innervated nuclei exclusively in the ipsilateral auditory brain stem. These include the lateral superior olive (LSO), ventral nucleus of the lateral lemniscus, medial superior olive, dorsomedial and ventromedial periolivary nuclei, and the MNTB itself. At the EM level the myelinated collaterals gave rise to terminals that contained nonround vesicles and, in the LSO, were seen terminating on cell bodies and primary dendrites. Responses of MNTB cells were similar to their primary excitatory input, the globular bushy cell (GBC), in a number of ways. The spontaneous spike rate of MNTB cells with low characteristic frequencies (CFs) was low, whereas it tended to be higher for higher CF units. In response to short tones, a low frequency MNTB cell showed enhanced phase-locking abilities, relative to auditory nerve fibers. For cells with CFs >1 kHz, the short tone response often resembled the primary-like with notch response seen in many globular bushy cells, with a well-timed onset component. Exceptions to and variations of this standard response were also noted. When compared with GBCs with comparable CFs, the latency of the MNTB cell response was delayed slightly, as would be expected given the synapse interposed between the two cell types. Our data thus confirm that, in the cat, the MNTB receives and converts synaptic inputs from globular bushy cells into a reasonably accurate reproduction of the bushy cell spike response. This MNTB cell output then becomes an important inhibitory input to a number of ipsilateral auditory brain stem nuclei.