Ventral Paraflocculus Research Articles

Altered functional connectivity among frontal eye fields, thalamus and cerebellum in bipolar disorder.

The aim of our study is to evaluate functional connectivity of cerebellothalamo-cortical networks linking frontal eye fields (FEF) and cerebellar regions associated with oculomotor control: nodulus (X), uvula (IX), flocculus (H X) and ventral paraflocculus (H IX) in bipolar disorder (BD) with the use of resting state functional magnetic resonance imaging (rsfMRI). 19 euthymic BD patients and 14 healthy controls underwent rsfMRI examination. Functional connectivity between bilateral FEF, thalamus and cerebellar regions associated with oculomotor control was evaluated. BD patients revealed decreased functional connectivity between following structures: right FEF and bilateral thalamus, flocculus (H X), uvula (IX); right thalamus and right FEF; between right flocculus (H X) and right FEF, left thalamus; between left thalamus and bilateral FEF and right flocculus (H X). BD patients presented decreased functional connectivity among FEF, thalamus and cerebellar structures associated with eye movements control. Oculomotor evaluation of BD patients assessed with rsfMRI may help to determine whether altered functional connectivity observed in our study is associated with eye movements deficits in BD.

The Macaque Cerebellar Flocculus Outputs a Forward Model of Eye Movement.

The central nervous system (CNS) achieves fine motor control by generating predictions of the consequences of the motor command, often called forward models of the movement. These predictions are used centrally to detect not-self generated sensations, to modify ongoing movements, and to induce motor learning. However, finding a neuronal correlate of forward models has proven difficult. In the oculomotor system, we can identify neuronal correlates of forward models vs. neuronal correlates of motor commands by examining neuronal responses during smooth pursuit at eccentric eye positions. During pursuit, torsional eye movement information is not present in the motor command, but it is generated by the mechanic of the orbit. Importantly, the directionality and approximate magnitude of torsional eye movement follow the half angle rule. We use this rule to investigate the role of the cerebellar flocculus complex (FL, flocculus and ventral paraflocculus) in the generation of forward models of the eye. We found that mossy fibers (input elements to the FL) did not change their response to pursuit with eccentricity. Thus, they do not carry torsional eye movement information. However, vertical Purkinje cells (PCs; output elements of the FL) showed a preference for counter-clockwise (CCW) eye velocity [corresponding to extorsion (outward rotation) of the ipsilateral eye]. We hypothesize that FL computes an estimate of torsional eye movement since torsion is present in PCs but not in mossy fibers. Overall, our results add to those of other laboratories in supporting the existence in the CNS of a predictive signal constructed from motor command information.

The entire trajectories of single pontocerebellar axons and their lobular and longitudinal terminal distribution patterns in multiple aldolase C-positive compartments of the rat cerebellar cortex.

The mammalian cerebellar cortex is compartmentalized, both anatomically and histochemically, into multiple parasagittal bands. To characterize the multiple zonal patterns of pontocerebellar mossy fiber projection, single neurons in the basilar pontine nucleus (BPN) were labeled by injecting biotinylated dextran amine into the BPN, and the entire axonal trajectory of single labeled neurons (n = 25) was reconstructed in relation to aldolase C compartments of Purkinje cells in rats. Single pontocerebellar axons, after passing through the contralateral middle cerebellar peduncle, ran transversely in the deep cerebellar white matter toward and often across the midline, and on their ways, gave rise to 2-10 primary collaterals at almost right angles in specific lobules only contralaterally or bilaterally with contralateral predominance. Each primary collateral further branched in a parasagittal plane to form a strip-shaped longitudinal termination zone with rosette-type swellings clustered in aldolase C-positive compartments in a single or multiple lobules, mainly in compartment 4+//5+, 5+//6+, and 6+//7+. Axons arising from the central, rostral, and lateral part of the BPN projected with multiple branches, mainly to simple lobule, crus II and paramedian lobule, to crus I and dorsal paraflocculus, and to ventral paraflocculus and lobule IXc, respectively. The results showed the pontocerebellar projection is closely related to lobular and compartmental organization of the cerebellum. A comparison of single axon morphologies of different mossy fiber systems indicates that the projection pattern of single pontocerebellar neurons with multiple collaterals innervating different longitudinal compartments arranged in a mediolateral direction represents a general feature of mossy fiber projection.

Choroid Plexus Cyst in a Neonatal Burmeister's Porpoise (Phocoena spinipinnis)

Neuroectodermal developmental anomalies are reported rarely in cetaceans and central nervous system cysts are not described. We describe the gross, microscopical, histochemical and immunohistochemical features of a neuraxial myelencephalic cyst in a stranded neonatal Burmeister's porpoise (Phocoena spinipinnis). Grossly, a subdural, extra-axial, well-demarcated, yellow fluid-filled cystic structure (1.9×1.6×1cm) expanded the left foramen of Luschka, the left caudolateral cerebellar recess and the left cranioventral myelencephalon. The cyst displaced the ipsilateral ventral paraflocculus and distended the underlying cranial nerves IX, X, XI and XII. Microscopically, the cystic structure was lined by a monolayer of low cuboidal to flattened epithelium supported by a thin fibrovascular matrix. Immunohistochemistry (IHC) revealed strong and diffuse expression of AE1/AE3 and focal positivity for vimentin. IHC for epithelial membrane antigen, glial fibrillary acid protein, synaptophysin and S100 was negative. Based on these findings, an extra-axial cyst of the choroid plexus of the fourth ventricle (CCPFV) was diagnosed. The pathological relevance of the CCPFV in this case is uncertain. The cause of death involved severe perinatal interspecific (shark) trauma. The present case provides the first evidence of a neuroepithelial cyst in cetacean species.

Searching for an Internal Representation of Stimulus Kinematics in the Response of Ventral Paraflocculus Purkinje Cells.

Motor control theories propose that the central nervous system builds internal representations of the motion of both our body and external objects. These representations, called forward models, are essential for accurate motor control. For instance, to produce a precise reaching movement to catch a flying ball, the central nervous system must build predictions of the current and future states of both the arm and the ball. Accumulating evidence suggests that the cerebellar cortex contains a forward model of an individual's body movement. However, little evidence is yet available to suggest that it also contains a forward model of the movement of external objects. We investigated whether Purkinje cell simple spike responses in an oculomotor region of the cerebellar cortex called the ventral paraflocculus contained information related to the kinematics of behaviorally relevant visual stimuli. We used a visuomotor task that obliges animals to track moving targets while keeping their eyes fixated on a stationary target to separate signals related to visual tracking from signals related to eye movement. We found that ventral paraflocculus Purkinje cells do not contain information related to the kinematics of behaviorally relevant visual stimuli; they only contain information related to eye movements. Our data stand in contrast with data obtained from cerebellar Crus I, wherein Purkinje cell discharge contains information related to moving visual stimuli. Together, these findings suggest specialization in the cerebellar cortex, with some areas participating in the computation of our movement kinematics and others computing the kinematics of behaviorally relevant stimuli.

Cerebellar Cortex Granular Layer Interneurons in the Macaque Monkey Are Functionally Driven by Mossy Fiber Pathways through Net Excitation or Inhibition

The granular layer is the input layer of the cerebellar cortex. It receives information through mossy fibers, which contact local granular layer interneurons (GLIs) and granular layer output neurons (granule cells). GLIs provide one of the first signal processing stages in the cerebellar cortex by exciting or inhibiting granule cells. Despite the importance of this early processing stage for later cerebellar computations, the responses of GLIs and the functional connections of mossy fibers with GLIs in awake animals are poorly understood. Here, we recorded GLIs and mossy fibers in the macaque ventral-paraflocculus (VPFL) during oculomotor tasks, providing the first full inventory of GLI responses in the VPFL of awake primates. We found that while mossy fiber responses are characterized by a linear monotonic relationship between firing rate and eye position, GLIs show complex response profiles characterized by “eye position fields” and single or double directional tunings. For the majority of GLIs, prominent features of their responses can be explained by assuming that a single GLI receives inputs from mossy fibers with similar or opposite directional preferences, and that these mossy fiber inputs influence GLI discharge through net excitatory or inhibitory pathways. Importantly, GLIs receiving mossy fiber inputs through these putative excitatory and inhibitory pathways show different firing properties, suggesting that they indeed correspond to two distinct classes of interneurons. We propose a new interpretation of the information flow through the cerebellar cortex granular layer, in which mossy fiber input patterns drive the responses of GLIs not only through excitatory but also through net inhibitory pathways, and that excited and inhibited GLIs can be identified based on their responses and their intrinsic properties.

Diversity of vestibular nuclei neurons targeted by cerebellar nodulus inhibition

A functional role of the cerebellar nodulus and ventral uvula (lobules X and IXc,d of the vermis) for vestibular processing has been strongly suggested by direct reciprocal connections with the vestibular nuclei, as well as direct vestibular afferent inputs as mossy fibres. Here we have explored the types of neurons in the macaque vestibular nuclei targeted by nodulus/ventral uvula inhibition using orthodromic identification from the caudal vermis. We found that all nodulus-target neurons are tuned to vestibular stimuli, and most are insensitive to eye movements. Such non-eye-movement neurons are thought to project to vestibulo-spinal and/or thalamo-cortical pathways. Less than 20% of nodulus-target neurons were sensitive to eye movements, suggesting that the caudal vermis can also directly influence vestibulo-ocular pathways. In general, response properties of nodulus-target neurons were diverse, spanning the whole continuum previously described in the vestibular nuclei. Most nodulus-target cells responded to both rotation and translation stimuli and only a few were selectively tuned to translation motion only. Other neurons were sensitive to net linear acceleration, similar to otolith afferents. These results demonstrate that, unlike the flocculus and ventral paraflocculus which target a particular cell group, nodulus/ventral uvula inhibition targets a large diversity of cell types in the vestibular nuclei, consistent with a broad functional significance contributing to vestibulo-ocular, vestibulo-thalamic and vestibulo-spinal pathways.

Tinnitus, Unipolar Brush Cells, and Cerebellar Glutamatergic Function in an Animal Model

Unipolar brush cells (UBCs) are excitatory interneurons found in the dorsal cochlear nucleus (DCN) and the granule cell layer of cerebellar cortex, being particularly evident in the paraflocculus (PFL) and flocculus (FL). UBCs receive glutamatergic inputs and make glutamatergic synapses with granule cells and other UBCs. It has been hypothesized that UBCs comprise local networks of tunable feed-forward amplifiers. In the DCN they might also participate in feed-back amplification of signals from higher auditory centers. Recently it has been shown that UBCs, in the vestibulocerebellum and DCN of adult rats, express doublecortin (DCX), previously considered a marker of newborn and migrating neurons. In an animal model, both the DCN, and more recently the PFL, have been implicated in contributing to the sensation of acoustic-exposure-induced tinnitus. These studies support the working hypothesis that tinnitus emerges after loss of peripheral sensitivity because inhibitory processes homeostatically down regulate, and excitatory processes up regulate. Here we report the results of two sequential experiments that examine the potential role of DCN and cerebellar UBCs in tinnitus, and the contribution of glutamatergic transmission in the PFL. In Experiment 1 it was shown that adult rats with psychophysical evidence of tinnitus induced by a single unilateral high-level noise exposure, had elevated DCX in the DCN and ventral PFL. In Experiment 2 it was shown that micro-quantities of glutamatergic antagonists, delivered directly to the PFL, reversibly reduced chronically established tinnitus, while similarly applied glutamatergic agonists induced tinnitus-like behavior in non-tinnitus controls. These results are consistent with the hypothesis that UBC up regulation and enhanced glutamatergic transmission in the cerebellum contribute to the pathophysiology of tinnitus.

小脳と眼球運動―視標追跡眼球運動をモデルとした基礎研究と臨床応用―

Recent studies implicate the cerebellum in cognitive functions in addition to its well-established roles in motor control and learning. Using a memory-based smooth-pursuit task that separates visual working memory from motor preparation and execution, monkeys were trained to pursue (i.e., go) or not pursue (i.e., no-go), a cued direction, based on the working memory of visual motion-direction and a go/no-go instruction. Task-related neuronal activity was examined in cerebral and cerebellar major smooth-pursuit pathways. Different cerebral and cerebellar areas carried distinctly different signals during memory-based smooth-pursuit. In the cerebellum, prediction-related signals (visual working memory, pursuit selection and movement preparation) were represented in the vermal lobules VI-VII and caudal fastigial nucleus, whereas the floccular region (flocculus and ventral paraflocculus) contained predominantly execution-related signals. This task was applied to patients with cerebellar degeneration and idiopathic Parkinson's disease (PD). None of the PD patients tested exhibited impaired working memory of motion-direction and/or go/no-go selection, but they did show task-specific difficulty in generating an initial smooth-pursuit component, suggesting difficulty in smooth-pursuit preparation. In contrast, most cerebellar patients exhibited impaired visual working memory in addition to difficulty in preparing for and executing smooth-pursuit. These results suggest different roles for the basal ganglia and cerebellum in smooth-pursuit planning.

Expression of doublecortin, a neuronal migration protein, in unipolar brush cells of the vestibulocerebellum and dorsal cochlear nucleus of the adult rat

Doublecortin (DCX) is a microtubule-associated protein that is critical for neuronal migration and the development of the cerebral cortex. In the adult, it is expressed in newborn neurons in the subventricular and subgranular zones, but not in the mature neurons of the cerebral cortex. By contrast, neurogenesis and neuronal migration of cells in the cerebellum continue into early postnatal life; migration of one class of cerebellar interneuron, unipolar brush cells (UBCs), may continue into adulthood. To explore the possibility of continued neuronal migration in the adult cerebellum, closely spaced sections through the brainstem and cerebellum of adult (3–16 months old) Sprague–Dawley rats were immunolabeled for DCX. Neurons immunoreactive (ir) to DCX were present in the granular cell layer of the vestibulocerebellum, most densely in the transition zone (tz), the region between the flocculus (FL) and ventral paraflocculus (PFL), as well as in the dorsal cochlear nucleus (DCN). These DCX-ir cells had the morphological appearance of UBCs with oval somata and a single dendrite ending in a brush. There were many examples of colocalization of DCX with Eps8 or calretinin, UBC markers. We also identified DCX-ir elements along the fourth ventricle and its lateral recess that had labeled somata but lacked the dendritic structure characteristic of UBCs. Labeled UBCs were seen in nearby white matter. These results suggest that there may be continued neurogenesis and/or migration of UBCs in the adult. Another possibility is that UBCs maintain DCX expression even after migration and maturation, reflecting a role of DCX in adult neuronal plasticity in addition to a developmental role in migration.

Golgi Cells Operate as State-Specific Temporal Filters at the Input Stage of the Cerebellar Cortex

Cerebellar processing of incoming information begins at the synapse between mossy fibers and granule cells, a synapse that is strongly controlled through Golgi cell inhibition. Thus, Golgi cells are uniquely positioned to control the flow of information into the cerebellar cortex and understanding their responses during behavior is essential to understanding cerebellar function. Here we show, for the first time, that Golgi cells express a unique oculomotor-related signal that can be used to provide state- and time-specific filtering of granule cell activity. We used newly established criteria to identify the unique electrophysiological signature of Golgi cells and recorded these neurons in the squirrel monkey ventral paraflocculus during oculomotor behaviors. We found that they carry eye movement, but not vestibular or visual, information and that this eye movement information is only expressed within a specific range of eye positions for each neuron. In addition, simultaneous recordings of Golgi cells and nearby mossy fibers revealed that Golgi cells have the opposite directional tuning of the mossy fiber(s) that likely drive their responses, and that these responses are more sluggish than their mossy fiber counterparts. Because the mossy fiber inputs appear to convey the activity of burst-tonic neurons in the brainstem, Golgi cell responses reflect a time-filtered negative image of the motor command sent to the extraocular muscles. We suggest a role for Golgi cells in the construction of forward models of movement, commonly hypothesized as a major function of the cerebellar cortex in motor control.

Mossy and climbing fiber collateral inputs in monkey cerebellar paraflocculus lobulus petrosus and hemispheric lobule VII and their relevance to oculomotor functions

Recent lesion studies on monkeys suggest that the cerebellar lobulus petrosus of the paraflocculus (LP) and crura I and II of hemispheric lobule VII (H-7) are involved in smooth pursuit eye movement control. To reveal the relationship between the LP and H-7, we studied mossy and climbing fiber collateral inputs to these areas in four cynamolgus monkeys. After unilateral injections of retrograde tracers into the LP, labeled mossy fibers were seen ipsilaterally in the crura I and II of H-7. A very small number of labeled mossy fiber collaterals were also seen in the dorsal paraflocculus (DP). Labeled climbing fibers were seen exclusively in the ipsilateral crus I. No labeled mossy/climbing fibers were seen in the flocculus, ventral paraflocculus and other cortical areas. Combined injections of fast blue in the LP and cholera toxin subunit B in the posterior crus I and crus II of H-7 resulted in a small number of the double-labeled pontine and principal olivary neurons. Combined injections in the LP and DP induced only a few double-labeled neurons in the pontine nuclei, and no double-labeled neurons in the olivary nuclei. These results suggest that the LP and crura I and II of H-7 may share some of their mossy and climbing fiber inputs and mediate similar functional roles involving smooth pursuit eye movement control.

Difference of climbing fiber input sources between the primate oculomotor-related cerebellar vermis and hemisphere revealed by a retrograde tracing study

The cerebellar flocculus–paraflocculus complex, vermal lobule VII (V-7) and hemispheric lobule VII (H-7) are involved in learning-dependent smooth pursuit eye movement control. To locate the sources of climbing fiber inputs to the H-7 and V-7, we injected retrograde tracers and examined the locations of retrogradely labeled neurons in the inferior olive in 4 monkeys. After the injection of cholera toxin B (CTB) into the H-7, retrogradely labeled neurons were observed abundantly in cell group d, i.e., dorsal cap, of the caudal medial accessory olive (MAO) and ventral lamella of principal olive (PO). After injections of fast blue (FB) into the V-7, retrogradely labeled neurons were observed mainly in cell group b of MAO, but rarely in cell group d or PO. Cell group d is known to receive inputs from the nucleus optic tract (NOT) and project climbing fibers to the flocculus and ventral paraflocculus, and cell group b is known to receive inputs from the superior colliculus. These results suggest that the three oculomotor cerebellar areas may use different visual signals for the control of smooth pursuit: the flocculus–paraflocculus complex and H-7 receive visual climbing fiber inputs derived mainly from the NOT via cell group d, while the V-7 receive visual climbing fiber inputs derived mainly from the superior colliculus via cell group b.

Neurophysiology and neuroanatomy of smooth pursuit: Lesion studies

Smooth pursuit impairment is recognized clinically by the presence of saccadic tracking of a small object and quantified by reduction in pursuit gain, the ratio of smooth eye movement velocity to the velocity of a foveal target. Correlation of the site of brain lesions, identified by imaging or neuropathological examination, with defective smooth pursuit determines brain structures that are necessary for smooth pursuit. Paretic, low gain, pursuit occurs toward the side of lesions at the junction of the parietal, occipital and temporal lobes (area V5), the frontal eye field and their subcortical projections, including the posterior limb of the internal capsule, the midbrain and the basal pontine nuclei. Paresis of ipsiversive pursuit also results from damage to the ventral paraflocculus and caudal vermis of the cerebellum. Paresis of contraversive pursuit is a feature of damage to the lateral medulla. Retinotopic pursuit paresis consists of low gain pursuit in the visual hemifield contralateral to damage to the optic radiation, striate cortex or area V5. Craniotopic paresis of smooth pursuit consists of impaired smooth eye movement generation contralateral to the orbital midposition after acute unilateral frontal or parietal lobe damage. Omnidirectional saccadic pursuit is a most sensitive sign of bilateral or diffuse cerebral, cerebellar or brainstem disease. The anatomical and physiological bases of defective smooth pursuit are discussed here in the context of the effects of lesion in the human brain.

Towards manipulative neuroscience based on brain-network -interface

Event Abstract Back to Event Towards manipulative neuroscience based on brain-network -interface Mitsuo Kawato1* 1 ATR Computational Neuroscience Labs, Japan The cerebellar internal model theory postulates that the cerebellar cortex acquires many internal models of controlled objects, dynamical processes in the external world dependent on long-term depression (LTD) of Purkinje cells. It predicts that the climbing fiber inputs to Purkinje cells carry the feedback motor command and can supervise learning of inverse dynamics models. Many experimental supports were obtained from the ventral paraflocculus of the cerebellum during monkey control of ocular following responses. fMRI studies mapped forward and inverse models of manipulated objects and tools in the cerebellar cortex. Kinetic models of LTD [1,2] suggest a cascade of excitable and bistable dynamical processes, which may resolve plasticity-stability dilemma at single spine level. That is, even a single pulse of climbing fiber input combined with an early train of several parallel fiber pulses can induce Ca2+ induced Ca2+ release via IP3 receptors on ER. The MAPK positive feedback loop leaky integrates resulting large Ca2+ elevation and if it crosses the threshold then the state moves to the depressed equilibrium. These models explain diverse LTD experiments and clearly demonstrate that LTD is a supervised learning rule, and not anti-Hebbian as erroneously characterized. The MAPK positive feedback loop model [1] was recently supported by a Ca2+ photo-uncaging and imaging experiment [3] that supports LTD all-or-none character. In [3], the most important information within the system, Ca2+ can be measured and manipulated directly, thus the theory was quite rigorously proved. At the system level, the cerebellar internal models for arm movements are still debated and we need to develop a method to directly manipulate information. In our "Understanding brain by Creating Brain"-approach, high-performance humanoid robots have been developed, and sensory-motor coordination problems were investigated. We explored several computational theories such as MOSAIC, imitation learning, biologically motivated robot biped locomotion, modular and hierarchical reinforcement learning models. Our paradigms include computational-model based imaging and non-invasive decoding of neural representations. However, we got frustrated that most experiments can show just temporal correlation between data and theory but not causality, unlike the above spine-level LTD story. We hope that manipulative neuroscience based on real time feedback of decoded neural information could be a resolution to this difficulty. Hierarchical Bayesian approach to combine fMRI and MEG, or NIRS and EEG, or neural decoding with machine learning techniques, and real-time control of robots with decoded information are expected to be key technological elements. Demonstrations of real-time robot hand control by decoded information from fMRI (http://www.atr.jp/html/topics/press_060526_e.html) in collaboration with Honda, control of a humanoid robot locomotion-like movements from monkey brain in collaboration with Miguel Nicolelis [4], prediction of wrist joint angular acceleration from the primary motor cortex currents estimated by hierarchical Bayesian MEG, or estimation of visual target velocity from MST currents, etc could be technical bases for this new approach.

Synchronized Firing among Retinal Ganglion Cells Signals Motion Reversal

We show that when a moving object suddenly reverses direction, there is a brief, synchronous burst of firing within a population of retinal ganglion cells. This burst can be driven by either the leading or trailing edge of the object. The latency is constant for movement at different speeds, objects of different size, and bright versus dark contrasts. The same ganglion cells that signal a motion reversal also respond to smooth motion. We show that the brain can build a pure reversal detector using only a linear filter that reads out synchrony from a group of ganglion cells. These results indicate that not only can the retina anticipate the location of a smoothly moving object, but that it can also signal violations in its own prediction. We show that the reversal response cannot be explained by models of the classical receptive field and suggest that nonlinear receptive field subunits may be responsible.

Zonal organization of the vestibulo-cerebellar pathways controlling the horizontal eye muscles using two recombinant strains of pseudorabies virus

Many studies have documented the influence of the flocculus upon vestibulo-ocular reflex eye movements. Electrical stimulation of Purkinje cells in a central longitudinal zone evoked slow ipsilateral eye movements in the horizontal plane. Recently, the organization of neurons in the vestibulo-cerebellar pathways controlling single lateral rectus and medial rectus muscles was identified in rats using the transynaptic transport of pseudorabies virus. Overlapping distributions of neurons innervating single muscles were located predominantly in a central longitudinal zone of ventral paraflocculi/dorsal flocculi, and the rostral half of ventral flocculi. This study used two isogenic pseudorabies virus recombinants to determine whether individual cells in those brain regions have collateralized projections to motoneuron pools innervating the right lateral rectus and the left medial rectus muscles using different survival times and dual injection paradigms. The infected neurons were detected using dual-labeling immunofluorescence. Three populations of labeled neurons were observed: two populations replicated only one reporter while a third contained both viruses (i.e. dual-labeled). Most dual-labeled cells were located in a central longitudinal zone of the ventral paraflocculus, ipsilateral to the injection into the medial rectus, whereas very few were in the flocculus. This finding suggests that the flocculus and ventral paraflocculus may exert influence upon distinct vestibulo-cerebellar pathways. Most Purkinje cells in the ventral paraflocculus may influence the vestibulo-ocular reflex pathways through collateralization, whereas those in the flocculus may instead provide a monocular control of eye movements.

Context contingent signal processing in the cerebellar flocculus and ventral paraflocculus during gaze saccades.

The vestibuloocular reflex (VOR) functions to stabilize gaze when the head moves. The flocculus region (FLR) of the cerebellar cortex, which includes the flocculus and ventral paraflocculus, plays an essential role in modifying signal processing in VOR pathways so that images of interest remain stable on the retina. In squirrel monkeys, the firing rate of most FLR Pk cells is modulated during VOR eye movements evoked by passive movement of the head. In this study, the responses of 48 FLR Purkinje cells, the firing rates of which were strongly modulated during VOR evoked by passive whole body rotation or passive head-on-trunk rotation, were compared to the responses generated during compensatory VOR eye movements evoked by the active head movements of eye-head saccades. Most (42/48) of the Purkinje cells were insensitive to eye-head saccade-related VOR eye movements. A few (6/48) generated bursts of spikes during saccade-related VOR but only during on-direction eye movements. Considered as a population FLR Pk cells were <5% as responsive to the saccade-related VOR as they were to the VOR evoked by passive head movements. The observations suggest that the FLR has little influence on signal processing in VOR pathways during eye-head saccade-related VOR eye movements. We conclude that the image-stabilizing signals generated by the FLR are highly dependent on the behavioral context and are called on primarily when external forces unrelated to self-generated eye and head movements are the cause of image instability.

Zonal organization of the vestibulo-cerebellum in the control of horizontal extraocular muscles using pseudorabies virus: I. flocculus/ventral paraflocculus

Much literature has studied the relationship between the organization of neurons in the flocculus/ventral paraflocculus and vestibulo-ocular reflex pathways. Although activation of a flocculus central zone produces ipsilateral horizontal eye movement, anatomical tracing evidence in rats suggests that there may not be a simple one-to-one correspondence between flocculus/ventral paraflocculus zones and control of single extraocular muscles or coplanar pairs of antagonistic extraocular muscles. This study used the retrograde transynaptic transport of pseudorabies virus to identify the topographical organization of Purkinje cells in the flocculus/ventral paraflocculus that control the lateral rectus (LR) and medial rectus (MR) muscles in rats. A survival time of 80 h and 84 h was necessary to observe consistent transynaptically labeled cells in the flocculus/ventral paraflocculus following injections of pseudorabies virus into the MR and LR, respectively. The organization of Purkinje cells in the dorsal flocculus and ventral paraflocculus abided by the traditional boundaries, whereas the labeling pattern in the ventral flocculus showed a more complex, interdigitated arrangement. In agreement with prior studies, transynaptically labeled neurons were also observed in specific vestibular nuclear regions within the medial and superior vestibular nuclei and dorsal Y group. The distribution of labeled neurons in ipsilateral and contralateral vestibular nuclei was associated with features of ipsilateral and contralateral retrograde labeling of Purkinje cells in flocculus/ventral paraflocculus. Importantly, this study provides the first evidence of vestibulo-cerebellar zones controlling individual extraocular muscles and also overlapping distribution of neurons in flocculo-vestibular zones that influence the LR and MR motoneuron pools. This suggests that some of these neurons may be responsible for controlling both muscles.

Collateralization of climbing and mossy fibers projecting to the nodulus and flocculus of the rat cerebellum

Collateralization of mossy and climbing fibers was investigated using cortical injections of cholera toxin b-subunit in the rat vestibulocerebellum. Injections were characterized by their retrograde labeling within the inferior olive. Collateral labeling was plotted using color-coded density profiles of the whole cerebellar cortex. Injections in the medial part of the nodulus resulted in olivary labeling that was restricted to the rostral part of the dorsal cap. Climbing fiber collaterals were found in medial and lateral nodular zones as well as in the ventral paraflocculus and adjacent flocculus. Injections in the intermediate part of the nodulus resulted in olivary labeling of the beta-subnucleus but could also involve the ventrolateral outgrowth. In the latter case, climbing fiber collaterals were found in the two floccular zones and in a small region in the lateral-most part of crus I. All nodular injections showed a bilaterally symmetric distribution of collateral mossy fiber rosettes that was mostly confined to the vestibulocerebellum and originated predominantly from the vestibular nuclei. Injections in the flocculus labeled the caudal part of the dorsal cap and/or the ventrolateral outgrowth. Mossy fiber rosettes were observed throughout the vestibulocerebellum but also included other regions of the cerebellar cortex in a bilaterally symmetric pattern corresponding with a more widespread precerebellar origin. Climbing fibers originating in the rostral dorsal cap, labeled from an injection in the ventral paraflocculus, collateralize to a medial and lateral zone in the nodulus. Climbing fiber collaterals were usually accompanied by subjacent labeling of mossy fiber rosettes. These results demonstrate that some nodular and floccular zones are related and, at least partially, share a common input.