Ventral Paraflocculus Research Articles

Location of efferent terminals of the primate flocculus and ventral paraflocculus revealed by anterograde axonal transport methods

Efferents of the flocculus (FL) and ventral paraflocculus (VP) were examined in seven anesthetized Macaca fuscata by anterograde axonal transport method using wheat germ agglutinin-conjugated horseradish peroxidase or phaseolus vulgaris leucoagglutinin. Several major foci of axon terminals were found in the vestibular nuclear complex and cerebellar nuclei. A difference was seen in the location of efferent terminals between the FL and VP. When the tracer covered the FL, labeled axon terminals were located within the medial and ventrolateral parts of the medial vestibular nucleus, superior vestibular nucleus and y-group. When the tracer covered the VP, labeled axon terminals were located within the caudo-ventral part of posterior interpositus and dentate nuclei, in addition to the medial and ventrolateral parts of the medial vestibular nucleus, superior vestibular nucleus and y-group. Labeled terminals were virtually absent in the basal interstitial nucleus of the cerebellum. On the points of neo- or paleo-cerebellar cortex fiber connections, these results correspond to our previous anatomical observations that the FL received mossy fiber afferents mainly from the vestibular system and nucleus reticularis tegmenti pontis and very little from the pontine nuclei, whereas the VP received mossy afferents mainly from the nucleus reticularis tegmenti pontis and pontine nuclei and very little from the vestibular system. These anatomical observations are consistent with a hypothesis in our previous anatomical and physiological study that the primate FL and VP mediate rather different functional roles in the oculomotor control.

1506 Cerebellar flocculus purkinje cell activities during head rotation in alert cats

The activity of cerebellar Purkinje cells was recorded in the ventral paraflocculus (VPFL) of alert monkeys during ocular following responses induced by brief movements of the visual scene. The mossy fiber input evoked ‘simple-spikes’ which increased their activity during either ipsiversive or downward motion of the visual scene. On the other hand, the ‘complex-spikes’ evoked by the climbing fiber input increased their activity during either contraversive or upward movement.To further define the sources of the visual input to the VPFL, we recorded single units in the dorsolateral pontine nucleus (DLPN), which is known to project to the VPFL as mossy fibers, and in the pretectal nucleus of the optic tract (NOT), which is known to project to the inferior olive whose neurons project to the cerebellum as climbing fibers. In both areas, most neurons were directionally selective, and responded to the moving visual scene with very short latencies (~40-60 ms). These results suggest that both DLPN and NOT neurons deliver information concerning movements of the visual scene to the VPFL through different pathways.

Pathways from cell groups of the paramedian tracts to the floccular region.

A group of cells lying along the midline of the mid-medulla, nucleus pararaphales, is shown to play a role in vertical eye movements. Its efferents project along the midline, then pass laterally to follow the ventral external arcuate fibers around the surface of the medulla into the restiform body. The fibers terminate in the flocculus and ventral paraflocculus. This nucleus is one of the "cell groups of the paramedian tracts," which, based on their connectivity, could provide a motor-feedback signal for eye-head position to the cerebellum. Lesions of these pathways could lead to gaze-evoked nystagmus.

Chapter 30 Visual inputs to cerebellar ventral paraflocculus during ocular following responses

The activity of cerebellar Purkinje cells was recorded in the ventral paraflocculus (VPFL) of alert monkeys during ocular following responses induced by brief movements of the visual scene. The mossy fiber input evoked 'simple-spikes' which increased their activity during either ipsiversive or downward motion of the visual scene. On the other hand, the 'complex-spikes' evoked by the climbing fiber input increased their activity during either contraversive or upward movement. To further define the sources of the visual input to the VPFL, we recorded single units in the dorsolateral pontine nucleus (DLPN), which is known to project to the VPFL as mossy fibers, and in the pretectal nucleus of the optic tract (NOT), which is known to project to the inferior olive whose neurons project to the cerebellum as climbing fibers. In both areas, most neurons were directionally selective, and responded to the moving visual scene with very short latencies (approximately 40-60 ms). These results suggest that both DLPN and NOT neurons deliver information concerning movements of the visual scene to the VPFL through different pathways.

Behavior and physiology of the macaque vestibulo-ocular reflex response to sudden off-axis rotation: Computing eye translation

The vestibulo-ocular reflex (VOR) has historically been considered a computationally simple reflex: to stabilize images on the retina against imposed head rotation, the eyes must be counterrotated by an equal amount in the opposite direction. During almost any head rotation, however, the eyes are also translated. We show that the VOR compensates for 90% of this translation, and suggest a computational scheme by which this is done, based on a temporal dissection of the VOR response to sudden head rotation. An initial response that corrects only for imposed rotation is refined by a series of three temporally delayed corrections of increasing complexity. The first correction takes only head rotation and viewing distance into account; the second, head rotation, viewing distance, and otolith translation; and the third, head rotation, viewing distance, otolith translation, and translation of the eyes relative to the otoliths. Responses of type I gaze velocity Purkije (GVP) cells in the cerebellar flocculus and ventral paraflocculus of rhesus monkeys were recorded during sudden head rotation. We show that cell discharge was modulated both by axis location and by viewing distance, suggesting that GVP cells play a role in the VOR response to rotation-induced eye translation.

Light-microscopic distribution and parasagittal organisation of muscarinic receptors in rabbit cerebellar cortex

Recent studies on the effects of intrafloccular injections of muscarinic agonists and antagonists on compensatory eye movements in rabbit, indicate that muscarinic receptors may play a modulatory role in the rabbit cerebellar circuitry. It was previously demonstrated by Neustadt et al. (1988), that muscarinic receptors in rabbit cerebellar cortex are distributed into alternating longitudinal zones of very high and very low receptor density. In the present study, the zonal and cellular distribution of muscarinic receptors in the rabbit cerebellar cortex is investigated in detail using in vitro ligand autoradiography with the non-selective high-affinity antagonist [ 3H]quinuclidinyl benzilate (QNB), and the M2-specific antagonist [ 3H]AF-DX384, and immunocytochemistry with a monoclonal antibody specific for the cloned m2 muscarinic receptor protein. [ 3H]QNB and [ 3H]AF-DX384 binding sites and m2-immunoreactivity had similar overall distributions: dense labeling occurred in the dendritec arbors of a subset of Purkinje cells that are organized into parasagittal bands. A high level of muscarinic receptor labeling was also observed in a thin substratum of the molecular layer immediately above the Purkinje cell layer of the vestibulo-cerebellar lobules, i.e. the nodulus, the ventral uvula and the flocculus. Labeling in this stratum was associated with densely packed fibres, which were putatively identified as parallel fibres. Also Golgi cells, which were localized in part in the molecular layer, and a subset of mossy fibre rosettes, primarily concentrated in lobule VI, were immunoreactive for the m2 receptor. The parasagittal bands of labeled Purkinje cell dendrites were most prominent in the anterior lobe (lobules I–V), in crus 1 and 2, in the flocculus, the ventral paraflocculus and the rostral folium of the nodulus. In other lobules, only infrequent Purkinje cells contained muscarinic receptors. The parasagittal organisation of muscarinic receptors differed from that of zebrin I, a Purkinje cell-specific protein which is often used as a marker of parasagittal parcelation of the cerebellar cortex. In the anterior lobe, however, there was a partial correspondence between muscarinic receptor and zebrin I bands. In the flocculus the distribution of muscarinic-receptor-positive Purkinje cells was related to the distinct white matter compartments as revealed with acetylcholinesterase (AChE) histochemistry. Muscarinic receptor-containing Purkinje cells were located primarily in the floccular zone 1, which is implicated in the control of eye movements about a horizontal axis. In order to relate the distribution of muscarinic receptor labeling to that of cholinergic nerve terminals, [ 3H]QNB binding sites and sodium-dependent [ 3H]hemicholinium-3 binding were compared. Sodium-dependent [ 3H]hemicholinium-3 binding sites mainly occurred in the granule cell layer of the vestibulo-cerebellum, which corresponds well with the distribution of the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT). However, sodium-dependent [ 3H]hemicholinium binding complemented, rather than co-localized with, muscarinic receptors which were primarily distributed in the molecular layer of the lobules of the vestibulo-cerebellar lobules. Their functional significance is puzzling, since their distribution does not correspond to that of markers of cholinergic innervation.

Anatomical compartments in the white matter of the rabbit flocculus

The white matter of the rabbit flocculus is subdivided into five compartments by narrow sheets of densely staining acetylcholinesterase-positive fibers. The most lateral compartment is continuous with the C2 compartment of the paraflocculus and contains the posterior interposed nucleus. The other four compartments are numbered from lateral to medial as floccular compartments 1, 2, 3, and 4 (FC1-4). FC1-3 continue across the posterolateral fissure into the adjacent folium (folium p) of the ventral paraflocculus. FC4 is present only in the rostral flocculus. In the caudal flocculus FC1 and FC3 abut dorsal to FC2. Fibers of FC1-4 can be traced into the lateral cerebellar nucleus and the floccular peduncle. The presence of acetylcholinesterase in the deep stratum of the molecular layer of the flocculus and ventral paraflocculus distinguishes them from the dorsal paraflocculus. The topographical relations to the flocculus and the floccular peduncle with group y and the cerebellar nuclei are discussed.

Zonal organization of the climbing fiber projection to the flocculus and nodulus of the rabbit: a combined axonal tracing and acetylcholinesterase histochemical study.

The localization and termination of olivocerebellar fibers in the flocculus and nodulus of the rabbit were studied with anterograde axonal transport methods [wheatgerm agglutinin-horseradish peroxidase (WGA-HRP) and tritiated leucine] and correlated with the compartments in the white matter of these lobules delineated with acetylcholinesterase histochemistry (Tan et al. J. Comp. Neurol., 1995, this issue). Olivocerebellar fibers originating from the caudal dorsal cap travel through floccular compartments FC2 and FC4 to terminate as climbing fibers in floccular zones FZII and FZIV. Fibers from the rostral dorsal cap and the ventrolateral outgrowth traverse compartments FC1 and FC3, which are interleaved with compartments FC2 and FC4, and terminate in zones FZI and FZIII. Fibers from the rostral pole of the medial accessory olive traverse the C2 compartment and terminate in the C2 zone. FZI-III extend into the adjoining folium (folium p) of the ventral paraflocculus. The C2 zone continues across folium p into other folia of the ventral paraflocculus and into the dorsal paraflocculus. Four compartments and five zones were distinguished in the nodulus. Medial compartment XC1 contains olivocerebellar fibers from the caudal dorsal cap and subnucleus beta that terminate in the XZI zone. Olivocerebellar fibers from the rostral dorsal cap and the ventrolateral outgrowth occupy XC2 and terminate in XZII. The XC4 compartment contains fibers from both the caudal dorsal cap and from the rostral dorsal cap and the ventrolateral outgrowth. The latter terminate in a central portion of the XZIV zone. The dorsomedial cell column projects to the XZIII zone, which is present only in the dorsal part of the nodulus. The rostral medial accessory olive projects to the XZV zone, which occupies the lateral border of the nodulus. These results confirm and extend the conclusions of Katayama and Nisimaru ([1988] Neurosci. Res. 5:424-438) on the zonal pattern in the olivo-nodular projection in the rabbit. Additional observations were made on the presence of a lateral A zone (Buisseret-Delmas [1988] Neurosci. Res. 5:475-493) in the hemisphere of lobules VI and VII. Retrograde labeling of the nucleo-olivary tract of Legendre and Courville ([1987] Neuroscience 21:877-891) was observed after WGA-HRP injections into the inferior olive including the rostral dorsal cap and the ventrolateral outgrowth. The anatomical and functional implications of these observations are discussed.

Cerebellovestibular projection from the posterior lobe cortex in the rabbit: an experimental study with the retrograde HRP method. I. Topographical relationships.

The sources of corticovestibular projections from the cerebellar posterior lobe vermis and hemisphere in the rabbit were investigated by the retrograde horseradish peroxidase (HRP) tracing method. Following iontophoretic injections into various subdivisions of the vestibular nuclear complex (VNC), labelled Purkinje neurones were identified ipsilaterally in all vermal lobules (VI through IX) and some regions of the hemisphere. The results indicate that projection is profuse and directed to all four nuclei of VNC. The labelling suggests some topographical relationships between lobules and especially sublobules of the posterior lobe and individual nuclei of VNC. The major projection originates from lobules VI and IX. A moderate projection derives from lobule VIII whereas that from lobule VII is small. Projections from the hemisphere arise mainly from crus I and crus II of the ansiform lobule. Those from the copula pyramidis, lobule HV and the ventral paraflocculus are sparse. In the present study a topographical relationships were more precisely established than before because the technique revealed VNC afferents from individual sublobules of the cerebellar posterior lobe cortex.

Cerebellovestibular projection from the posterior lobe cortex in the rabbit: an experimental study with the retrograde HRP method. II. Zonal organization.

The mediolateral distribution of neurones of origin of the corticovestibular projection from the cerebellar posterior lobe in the rabbit was studied with the retrograde horseradish peroxidase (HRP) tracing method. After iontophoretic injections confined to various subdivisions of the vestibular nuclear complex (VNC) labelled Purkinje neurones were found ipsilaterally in widespread mediolateral cortical regions of vermal lobules from VI to IX, as well as in crus I and crus II of the ansiform lobule, the copula pyramidis, lobule HV and the ventral paraflocculus. However, when projections from individual sublobules were examined, a clearly visible zonal pattern was found. Thus, Purkinje neurones projecting to VNC were arranged in longitudinal bands with medial and lateral boundaries quite well demarcated. These bands had a different width and were found to be located at different distances from the midline. The present findings constitute the first indication of a zonal organization of corticovestibular projections from individual sublobules of the cerebellar posterior lobe in the rabbit. This zonal arrangement of VNC afferents is discussed with the special emphasis on the cerebellar longitudinal zones and related to previous studies on other species.

Non-Reciprocal Connections between the Perihypoglossal Nuclei and the Cerebellar Paramedian Lobule in Rabbits and Their Relationship to the Climbing Fiber Zones

Retrogradely transported horseradish peroxidase (HRP) was used to investigate the organization of projections from the perihypoglossal nuclei to the cerebellar paramedian lobule, and possible reciprocal corticoperihypoglossal connections in rabbits. The absence of labeled Purkinje cells in the paramedian lobule after HRP injections of the perihypoglossal nuclei, compared with labeling in the nodulus, ipsilateral flocculus and adjacent ventral paraflocculus, strongly suggests that corticoperihypoglossal projections do not originate in the paramedian lobule. Comparison of labeling patterns in the perihypoglossal nuclei following HRP injections into various sublobules of the paramedian lobule suggests that projections from the perihypoglossal nuclei to the paramedian lobule exist and that some degree of topographic organization is present exclusively in bilateral projections from the caudal part of nucleus prepositus hypoglossi. All perihypoglossal projections end in deep parts of sublobules e-b of zones C2 and D1 (as defined by inferior olivary labeling). It is significant that in the ipsilateral nucleus prepositus hypoglossi, two groups of cells projecting to zone C2 are arranged rostrocaudally between three other groups projecting to zone D1.

Visual pontocerebellar projections in the macaque

The cerebellum plays an important role in the visual guidance of movement. In order to understand the anatomical basis of visuomotor control, we studied the projection of pontine visual cells onto the cerebellar cortex of monkeys. Wheat germ agglutinin horseradish peroxidase was injected into the dorsolateral pons two monkeys. Retrogradely labelled cells were mapped in the cerebral cortex and superior colliculus, and orthogradely labelled fibers in the cerebellar cortex. The largest number of retrogradely labelled cells in the cerebral cortex was in a group of medial extrastriate visual areas. The major cerebellar target of these dorsolateral pontine cells is the dorsal paraflocculus. There is a weaker projection to the uvula, paramedian lobe, and Crus II, and a sparse but definite projection to the ventral paraflocculus. There are virtually no projections to the flocculus. There are sparse ipsilateral pontocerebellar projections to these same regions of cerebellar cortex. In nine monkeys, we made small injections of the tracer into the cerebellar cortex and studied the location of retrogradely filled cells in the pontine nuclei and inferior olive. Injections into the dorsal paraflocculus or rostral folia of the uvula retrogradely labelled large numbers of cells in the dorsolateral region of the contralateral pontine nuclei. Labelled cells were found ipsilaterally, but in reduced numbers. Injections outside of these areas in ventral paraflocculus or paramedian lobule labelled far fewer cells in this region of the pons. We conclude that the principal source of cerebral cortical visual information arises from a medial group of extrastriate visual areas and is relayed through cells in the dorsolateral pontine nuclei. The principal target of pontine visual cells is the dorsal paraflocculus.

Responses during eye movements of brain stem neurons that receive monosynaptic inhibition from the flocculus and ventral paraflocculus in monkeys.

1. We have identified a group of brain stem cells called "flocculus target neurons" (or FTNs) because they are inhibited at monosynaptic latencies by stimulation of the flocculus and the ventral paraflocculus with single electrical pulses. We report the responses of FTNs, as well as those of other brain stem cells, during horizontal eye movements with the head stationary and during natural vestibular stimulation in monkeys. 2. FTNs discharged primarily in relation to eye movements. The majority (71%) showed increased firing for eye movement away from the side of the recording ("contraversive"), which is consistent with their inhibition by Purkinje cells that show increased firing for eye movement toward the side of recording. However, a significant and surprisingly large percentage (29%) of FTNs showed increased firing for eye movement toward the side of recording ("ipsiversive"). 3. The firing rate of FTNs showed strong modulation during pursuit of sinusoidal target motion with the head stationary and during the compensatory eye movements evoked by fixation of an earth-stationary target with sinusoidal head rotation. In addition, firing rate was related to eye position during steady fixation at different positions. Of the FTNs that showed increased firing for contraversive eye motion during pursuit with the head stationary, most had an infection in the relationship between firing rate and eye position so that the sensitivity to eye position was low for eye positions ipsilateral to straight-ahead gaze and high for eye positions contralateral to straight-ahead gaze. 4. When the monkey canceled the vestibuloocular reflex (VOR) by tracking a target that moved exactly with him during sinusoidal head rotation, the firing rate of FTNs was modulated much less strongly than during pursuit with the head stationary. In the FTNs that showed increased firing for contraversive eye motion during pursuit, firing rate during cancellation of the VOR increased for contraversive head motion during sinusoidal vestibular rotation at 0.4 Hz but was only weakly modulated during rotation at 0.2 Hz. 5. The position-vestibular-pause cells (PVP-cells), previously identified as interneurons in the disynaptic VOR pathways, were not inhibited by stimulation of the flocculus and ventral paraflocculus and had response properties that were different from FTNs. The majority (69%) showed increased firing for contraversive eye motion during pursuit and for ipsiversive head motion during cancellation of the VOR, whereas some (31%) showed the opposite direction preferences under both conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Neural basis for motor learning in the vestibuloocular reflex of primates. III. Computational and behavioral analysis of the sites of learning

1. We have used a combination of eye movement recordings and computer modeling to study long-term adaptive modification (motor learning) in the vestibuloocular reflex (VOR). The eye movement recordings place constraints on possible sites for motor learning. The computer model abides by these constraints, as well as constraints provided by data in previous papers, to formalize a new hypothesis about the sites of motor learning. The model was designed to reproduce as much of the existing neural and behavioral data as possible. 2. Motor learning was induced in monkeys by fitting them with spectacles that caused the gain of the VOR (eye speed divided by head speed) to increase to values > 1.6 or to decrease to values < 0.4. We elicited pursuit by providing ramp motion of a small target at 30 degrees/s along the horizontal axis. Changes in the gain of the VOR caused only small and inconsistent changes in the eye acceleration in the first 100 ms after the onset of pursuit and had no effect on the eye velocity during tracking of steady target motion. Electrical stimulation in the flocculus and ventral paraflocculus with single pulses or trains of pulses caused smooth eye movement toward the side of stimulation after latencies of 9-11 ms. Neither the latency, the peak eye velocity, nor the initial eye acceleration varied as a consistent function of the gain of the VOR. 3. The computer model contained nodes that represented position-vestibular-pause cells (PVP-cells) and flocculus target neurons (FTNs) in the vestibular nucleus, and horizontal gaze-velocity Purkinje cells (HGVP-cells) in the cerebellar flocculus and ventral paraflocculus. Node FTN represented only the "E-c FTNs," which show increased firing for eye motion away from the side of recording. The transfer functions in the model included dynamic elements (filters) as well as static elements (summing junctions, gain elements, and time delays). Except for the transfer functions that converted visual motion inputs into commands for smooth eye movement, the model was linear. 4. The performance of the model was determined both by computer simulation and, for the VOR in the dark, by analytic solution of linear equations. For simulation, we adjusted the parameters by hand to match the output of the model to the eye velocity of monkeys and to match the activity of the relevant nodes in the model to the firing of HGVP-cells, FTNs, and PVP-cells when the gain of the VOR was 0.4, 1.0, and 1.6.(ABSTRACT TRUNCATED AT 400 WORDS)

Neural basis for motor learning in the vestibuloocular reflex of primates. II. Changes in the responses of horizontal gaze velocity Purkinje cells in the cerebellar flocculus and ventral paraflocculus

1. We made extracellular recordings from Purkinje cells in the flocculus and ventral paraflocculus of awake monkeys before and after motor learning in the vestibuloocular reflex (VOR). Three samples were recorded 1) after miniaturizing spectacles had reduced the gain of the VOR (eye speed divided by head speed) to 0.4; 2) when the gain of the VOR was near 1.0; and 3) after magnifying spectacles had increased the gain of the VOR to 1.6. 2. We studied Purkinje cells that showed stronger modulation of simple-spike firing rate during horizontal than during vertical pursuit. These cells corresponded to the previously identified "horizontal gaze velocity Purkinje cells" or HGVP-cells. During pursuit of smooth target motion with the head stationary, HGVP-cells showed strong modulation of firing rate with increases for ipsiversive eye motion (toward the side of recording). When the monkey canceled his VOR by tracking a target that moved exactly with him during sinusoidal head rotation in the horizontal plane, HGVP-cells again showed strong modulation of firing rate with increases for ipsiversive head motion. 3. The responses of HGVP-cells during pursuit with the head stationary and during cancellation of the VOR reveal separate components of firing rate related to eye and head velocity. We used these two behavioral conditions to test for effects of motor learning on the head and eye velocity components of the simple-spike firing of HGVP-cells. Our data confirm the previous observation that motor learning causes the sensitivity to head velocity to be larger when the gain of the VOR is high and smaller when the gain of the VOR is low. Thus we agree with the previous conclusion that changes in the vestibular sensitivity of HGVP-cells, measured during sinusoidal head motion at low frequencies, are in the wrong direction to cause changes in the gain of the VOR. 4. To determine whether the simple-spike output from the HGVP-cells plays a role in the VOR after motor learning, we recorded simple-spike firing during the VOR evoked by transient, rapid changes in head velocity in darkness. When the gain of the VOR was low, firing rate increased during the VOR evoked by ipsiversive head motion and decreased during the VOR evoked by contraversive head motion. When the gain of the VOR was high, the direction selectivity of the responses was reversed.(ABSTRACT TRUNCATED AT 400 WORDS)

Neural basis for motor learning in the vestibuloocular reflex of primates. I. Changes in the responses of brain stem neurons.

1. We recorded from neurons in the brain stem of monkeys before and after they had worn magnifying or miniaturizing spectacles to cause changes in the gain of the vestibuloocular reflex (VOR). The gain of the VOR was estimated as eye speed divided by head speed during passive horizontal head rotation in darkness. Electrical stimulation in the cerebellum was used to identify neurons that receive inhibition at monosynaptic latencies from the flocculus and ventral paraflocculus (flocculus target neurons or FTNs). Cells were studied during smooth pursuit eye movements with the head stationary, fixation of different positions, cancellation of the VOR, and the VOR evoked by rapid changes in head velocity. 2. FTNs were divided into two populations according to their responses during pursuit with the head stationary. The two groups showed increased firing during smooth eye motion toward the side of recording (Eye-ipsiversive or E-i) or away from the side of recording (Eye-contraversive or E-c). A higher percentage of FTNs showed increased firing rate for contraversive pursuit when the gain of the VOR was high (> or = 1.6) than when the gain of the VOR was low (< or = 0.4). 3. Changes in the gain of the VOR had a striking effect on the responses during the VOR for the FTNs that were E-c during pursuit with the head stationary. Firing rate increased during contraversive VOR eye movements when the gain of the VOR was high or normal and decreased during contraversive VOR eye movements when the gain of the VOR was low. Changes in the gain of the VOR caused smaller changes in the responses during the VOR of FTNs that were E-i during pursuit with the head stationary. We argue that motor learning in the VOR is the result of changes in the responses of individual FTNs. 4. The responses of E-i and E-c FTNS during cancellation of the VOR depended on the gain of the VOR. Responses tended to be in phase with contraversive head motion when the gain of the VOR was low and in phase with ipsiversive head motion when the gain of the VOR was high. Comparison of the effect of motor learning on the responses of FTNs during cancellation of the VOR with the results of similar experiments on horizontal-gaze velocity Purkinje cells in the flocculus and ventral paraflocculus suggests that the brain stem vestibular inputs to FTNs are one site of motor learning in the VOR.(ABSTRACT TRUNCATED AT 400 WORDS)

The unipolar brush cells of the rat cerebellar cortex and cochlear nucleus are calretinin-positive: a study by light and electron microscopic immunocytochemistry.

Cell class-specific markers are powerful tools for the study of individual neuronal populations. The peculiar unipolar brush cells of the mammalian cerebellar cortex have only recently been definitively identified by means of the Golgi method, and we have explored markers of cerebellar neurons with the purpose of facilitating the analysis of this new cell population and, especially, its distribution and ultrastructural features. By light microscopic immunocytochemistry, we demonstrate that, in the rat, the unipolar brush cells are the cortical neurons that are most densely immunostained with antiserum to calretinin, a recently discovered calcium-binding protein. The unipolar brush cells are highly concentrated in the flocculo-nodular lobe, the ventral uvula and the ventral paraflocculus, occur at relatively high density in the lingula, at moderate-to-low density in other folia of the vermis and in the narrow intermediate cortex, and at low to very low density, with the exception of a few hot spots, in the lateral regions of the cerebellar hemispheres and in the dorsal paraflocculus. Unipolar brush cells are also found in the cochlear nucleus. In addition to the unipolar brush cells, calretinin antibody distinctly stains certain mossy fibers, and weakly to moderately stains other cerebellar elements, such as granule neurons and climbing fibers. In the lobules containing high densities of unipolar brush cells, the granule cell bodies and the parallel fibers are much less immunoreactive, and there are many more densely immunostained mossy fibers than in the lobules, where these cells are rare, which suggests some relationships between these elements. In the cerebellar nuclei, small neurons are densely immunostained, while large neurons are immunonegative. The unipolar brush cells reside nearly exclusively in the granular layer. They are small neurons, intermediate in size between granule cells and Golgi cells, and their features are remarkably similar across all lobules. They usually have a single, relatively thick dendrite of varying length that terminates in a brush-like tip consisting of several short branchlets. Utilizing a pre-embedding protocol, we have identified unipolar brush cells with the electron microscope. The cytoplasm of these cells is partially obscured by the electron dense product of calretinin immunoreaction in all regions of the soma and processes. The cells are often covered with non-synaptic appendages and contain a peculiar cytoplasmic inclusion consisting of ringlet subunits. Other characteristic components are numerous neurofilaments, mitochondria and large, dense-core vesicles. Individual brushes enter one or two glomeruli, where the dendritic branchlets establish an unusually extensive synapse with mossy fiber rosettes.(ABSTRACT TRUNCATED AT 400 WORDS)

Climbing fiber inputs to monkey cerebellar ventral paraflocculus during ocular following responses

Climbing fiber inputs to monkey cerebellar ventral paraflocculus during ocular following responses

Unusual neurofilament composition in cerebellar unipolar brush neurons.

During antibody screening on sections of rat cerebellum, we noticed a group of small neurons which exhibited unusual staining properties. They were robustly immunopositive for the high molecular weight neurofilament protein, moderately immunostained with antibodies to the low molecular weight neurofilament protein and alpha-internexin, but only faintly immunoreactive (in PAP sections) or essentially immunonegative (in immunofluorescent sections) with all members of a panel of antibodies directed against the middle molecular weight neurofilament protein. Since neurons generally react equally well with phosphate-independent, (antibodies to) low, middle and high molecular weight neurofilament protein, we conclude that middle molecular weight neurofilament protein is present in these cells in an unusually low relative amount. These cells are found in the granular layer and appear concentrated in the flocculus, ventral paraflocculus, and vermis, particularly in the ventral uvula and nodulus (lobules IXd and X). Previous studies performed by Hockfield defined a population of neurons of similar appearance and distribution using the monoclonal antibody Rat-302, which recognized an uncharacterized 160 kDa protein. We show here that the cells described by Hockfield are identical to those we have found and furthermore that the Rat-302 antibody specifically recognizes the dephosphorylated form of the lysine-serine-proline repeated sequences of high molecular weight neurofilament protein. These cells were studied by pre-embedding immunoelectron microscopy. The nucleus is deeply indented and shows little condensed chromatin. The cytoplasm contains scattered microtubules and a larger number of neurofilaments than expected in a small cell. There are numerous large dense core vesicles, an unusual organelle consisting of ringlet subunits, and relatively little granular endoplasmic reticulum. A thin axon and a single stout dendritic trunk emanate from the perikaryon. Although the cell body and the dendritic shaft may form either complex contacts with mossy fibres (resembling those previously termed en marron synapses) or simple symmetric synapses with small boutons containing pleomorphic vesicles, most of the synaptic relations are established on the shafts of brush-like branchlets that form at the tip of the dendrite and enter one or two glomeruli. Each branchlet forms an extraordinarily extensive asymmetric synapse with the mossy fibre rosette and the subsynaptic region shows a microfibrillar web connected to the postsynaptic density. In addition to other organelles, the branchlets contain numerous mitochondria and large dense core vesicles. Short, non-synaptic appendages with few cytoplasmic organelles emanated from the cell body, dendritic shaft and branchlets.(ABSTRACT TRUNCATED AT 400 WORDS)

Inverse-dynamics model eye movement control by Purkinje cells in the cerebellum.

Many lines of evidence suggest that the cerebellum is involved in motor control. But what features of these movements are encoded by cerebellar neurons? For slow-tracking eye movements, the activity of Purkinje cells in the ventral paraflocculus of the cerebellum is known to be correlated with eye velocity and acceleration. Here we show that the complex temporal pattern of the firing frequency that occurs during the ocular following response elicited by movements of a large visual scene can be reconstructed by an inverse-dynamics representation, which uses the position, velocity and acceleration of eye movements. Further analysis reveals that the velocity and acceleration components can provide appropriate dynamic drive signals to ocular motor neurons, whereas the position component often has the wrong polarity. We conclude that these Purkinje cells primarily contribute dynamic command signals.