Vermal Lobules VII Research Articles

Disynaptic Subthalamic Input to the Posterior Cerebellum in Rat.

In the last decade, the interplay between basal ganglia and cerebellar functions has been increasingly advocated to explain their joint operation in both normal and pathological conditions. Yet, insight into the neuroanatomical basis of this interplay between both subcortical structures remains sparse and is mainly derived from work in primates. Here, in rodents, we have studied the existence of a potential disynaptic connection between the subthalamic nucleus (STN) and the cerebellar cortex as has been demonstrated earlier for the primate. A mixture of unmodified rabies virus (RABV: CVS 11) and cholera toxin B-subunit (CTb) was injected at places in the posterior cerebellar cortex of nine rats. The survival time was chosen to allow for disynaptic retrograde transneuronal infection of RABV. We examined the STN for neurons infected with RABV in all nine cases and related the results with the location of the RABV/CTb injection site, which ranged from the vermis of lobule VII, to the paravermis and hemispheres of the paramedian lobule and crus 2a. We found that cases with injection sites in the vermis of lobule VII showed prominent RABV labeling in the STN. In contrast, almost no subthalamic labeling was noted in cases with paravermal or hemispheral injection sites. We show circumstantial evidence that not only the pontine nuclei but also the pedunculotegmental nucleus may act as the intermediary in the connection from STN to cerebellar cortex. This finding implies that in the rat the STN links disynaptically to the vermal part of lobule VII of the cerebellar cortex, without any major involvement of the cerebellar areas that are linked to sensorimotor functions. As vermal lobule VII recently has been shown to process disynaptic input from the retrosplenial and orbitofrontal cortices, we hypothesize that in the rat the subthalamic input to cerebellar function might be used to influence more prominently non-motor functions of the cerebellum than motor functions. This latter aspect seems to contradict the primate results and could point to a more elaborate interaction between basal ganglia and cerebellum in more demanding motor tasks.

Intermittent theta-burst stimulation of the lateral cerebellum increases functional connectivity of the default network.

Cerebral cortical intrinsic connectivity networks share topographically arranged functional connectivity with the cerebellum. However, the contribution of cerebellar nodes to distributed network organization and function remains poorly understood. In humans, we applied theta-burst transcranial magnetic stimulation, guided by subject-specific connectivity, to regions of the cerebellum to evaluate the functional relevance of connections between cerebellar and cerebral cortical nodes in different networks. We demonstrate that changing activity in the human lateral cerebellar Crus I/II modulates the cerebral default mode network, whereas vermal lobule VII stimulation influences the cerebral dorsal attention system. These results provide novel insights into the distributed, but anatomically specific, modulatory impact of cerebellar effects on large-scale neural network function.

Frontocerebellar connectivity: climbing through the inferior olive

Frontocerebellar connectivity: climbing through the inferior olive

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.

Functional topography in the human cerebellum: A meta-analysis of neuroimaging studies

Clinical, experimental and neuroimaging studies indicate that the cerebellum is involved in neural processes beyond the motor domain. Cerebellar somatotopy has been shown for motor control, but topographic organization of higher-order functions has not yet been established. To determine whether existing literature supports the hypothesis of functional topography in the human cerebellum, we conducted an activation likelihood estimate (ALE) meta-analysis of neuroimaging studies reporting cerebellar activation in selected task categories: motor ( n = 7 studies), somatosensory ( n = 2), language ( n = 11), verbal working memory ( n = 8), spatial ( n = 8), executive function ( n = 8) and emotional processing ( n = 9). In agreement with previous investigations, sensorimotor tasks activated anterior lobe (lobule V) and adjacent lobule VI, with additional foci in lobule VIII. Motor activation was in VIIIA/B; somatosensory activation was confined to VIIIB. The posterior lobe was involved in higher-level tasks. ALE peaks were identified in lobule VI and Crus I for language and verbal working memory; lobule VI for spatial tasks; lobules VI, Crus I and VIIB for executive functions; and lobules VI, Crus I and medial VII for emotional processing. Language was heavily right-lateralized and spatial peaks left-lateralized, reflecting crossed cerebro-cerebellar projections. Language and executive tasks activated regions of Crus I and lobule VII proposed to be involved in prefrontal-cerebellar loops. Emotional processing involved vermal lobule VII, implicated in cerebellar-limbic circuitry. These data provide support for an anterior sensorimotor vs. posterior cognitive/emotional dichotomy in the human cerebellum. Prospective studies of multiple domains within single individuals are necessary to better elucidate neurobehavioral structure–function correlations in the cerebellar posterior lobe.

Independent roles for the dorsal paraflocculus and vermal lobule VII of the cerebellum in visuomotor coordination

Two distinct areas of cerebellar cortex, vermal lobule VII and the dorsal paraflocculus (DPFl) receive visual input. To help understand the visuomotor functions of these two regions, we compared their afferent and efferent connections using the tracers wheatgerm agglutinin horseradish peroxidase (WGA-HRP) and biotinilated dextran amine (BDA). The sources of both mossy fibre and climbing fibre input to the two areas are different. The main mossy fibre input to lobule VII is from the nucleus reticularis tegmenti pontis (NRTP), which relays visual information from the superior colliculus, while the main mossy fibre input to the DPFl is from the pontine nuclei, relaying information from cortical visual areas. The DPFl and lobule VII both also receive mossy fibre input from several common brainstem regions, but from different subsets of cells. These include visual input from the dorsolateral pons, and vestibular-oculomotor input from the medial vestibular nucleus (MVe) and the nucleus prepositus hypoglossi (Nph). The climbing fibre input to the two cerebellar regions is from different subdivisions of the inferior olivary nuclei. Climbing fibres from the caudal medial accessory olive (cMAO) project to lobule VII, while the rostral MAO (rMAO) and the principal olive (PO) project to the DPFl. The efferent projections from lobule VII and the DPF1 are to all of the recognised oculomotor and visual areas within the deep cerebellar nuclei, but to separate territories. Both regions play a role in eye movement control. The DPFl may also have a role in visually guided reaching.

The pontocerebellar projection: longitudinal zonal distribution of fibers from discrete regions of the pontine nuclei to vermal and parafloccular cortices in the rat

A longitudinal parasagittal organization (alternating labeled and unlabeled stripes) of mossy fiber terminals in the paraflocculus and in the vermal lobule VII of the cerebellum was found after small injections (less than 50 nl) of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into discrete regions of the basilar pontine nuclei (BPN) of rats. Up to three stripes were found within the paraflocculus of both sides, following injections (of about 500 μm in diameter) in either the medial or lateral region of the caudal half of the BPN. Up to five stripes were found in the vermal lobule VII after similar size injections into the rostro-ventral region of the BPN. These results emphasize the possibility that the parasagittal zonal arrangement could be a common pattern of organization shared by climbing and mossy fiber afferents.

Differential modulation of Purkinje cell activity by enkephalin and corticotropin releasing factor

Several peptides have been localized within afferents to the opossum's cerebellum, including cholecystokinin (15), enkephalin (16, 17) and corticotropin releasing factor (7, 9). Each of these peptides has a heterogeneous laminar and lobular distribution. Two peptides, enkephalin (ENK) and corticotropin releasing factor (CRF) are present in specific populations of climbing fibers and mossy fibers, which have an overlapping distribution in several areas of the cerebellum, in particular the lateral aspect of vermal lobules VII and VIII. Within this location ENK and CRF are co-localized in individual climbing fibers and mossy fibers (7). In the present study, the physiological effects of these peptides on Purkinje cell activity were analyzed. The data indicate that ENK and CRF have opposite effects on Purkinje cell activity. ENK suppresses spontaneous activity as well as that induced by application of glutamate and aspartate, as described previously (5). In contrast, CRF enhances both spontaneous and amino acid-induced unit activity. Further, when applied simultaneously, CRF blocks the suppressive effect induced by ENK. Previous studies have shown that climbing fibers, as well as the mossy fiber-parallel fiber pathway, are excitatory to Purkinje cells (11). However, immunohistochemical data have shown that these afferents are heterogeneous with respect to their chemical content (7–9, 15–17, 25). As found in the current and previous studies (3, 5) peptides in climbing and mossy fibers modulate the responsiveness of Purkinje cells to primary excitatory neurotransmitters in selected areas of the cerebellar cortex. However, the firing rate of individual Purkinje cells is differentially altered depending on which neurochemical messenger(s) are released. Thus, within circumscribed lobules of the cerebellum, activation of a climbing fiber or the mossy fiberparallel fiber pathway may not always result in a stereotypical excitation of their target neurons. The release of neuromodulators with the primary neurotransmitter may lead to a modification of the response. Thus, a wide range of responses following activation of a single afferent fiber is possible leading to synaptic plasticity in cerebellar circuitry.

Direction-selective saccadic-burst neurons in the fastigial oculomotor region of the macaque

Discharges of 68 neurons, recorded from the oculomotor region of the fastigial nucleus (FN) of the macaque, were characterized by a burst which started approximately 20 msec prior to the onset of a saccade in a direction contralateral to the recording site. These fastigial neurons also paused before saccades in their nonpreferred direction and then discharged with a subsequent burst. All units were spontaneously active but the tonic level of activity did not reflect eye position. They aggregated within the oculomotor region and the firing of 57 units (83.8%) was suppressed by stimulation of vermal lobule VII. Tonic discharges of six other units were closely related to eye position and located rostral to the burst units. Discharges of 16 units increased during the ipsilateral phase of sinusoidal head rotation and those of 50 units increased during contralateral head rotation. These neurons did not show saccade-related activity. They were widely scattered in the rostral and central portions of the FN. None of these units was inhibited by stimulation of vermal lobule VII.

Olivocerebellar and cerebelloolivary connections of the oculomotor region of the fastigial nucleus in the macaque monkey

Anatomical connections of the caudal portion of the fastigial nucleus (FN) with the inferior olive (IO) were studied in macaque monkeys with wheat-germ-agglutinin-conjugated horseradish peroxidase (WGA/HRP) and HRP. When injected HRP was confined to a caudal portion of the FN, retrogradely labeled Purkinje cells (P cells) appeared in the oculomotor vermis. We defined the area that receives the projection from vermal lobule VII as the fastigial oculomotor region. The same HRP injection resulted in retrograde labeling of IO neurons in an area of group b (of Bowman and Sladek: J. Comp. Neurol. 152:299-316, '73) of the contralateral medial accessory olive (MAO). This area was designated as the Z-portion because in the coronal section it appears like the letter "Z." Retrogradely labeled IO neurons were also found in the Z-portion when HRP was injected into the oculomotor vermis, indicating that neurons in this portion project to both the fastigial and vermal oculomotor regions. Anterogradely labeled axons from the contralateral fastigial oculomotor region also terminated in the Z-portion. When the effective site included a region anterior to the fastigial oculomotor region, labeled P cells appeared in lobule V and labeled IO neurons appeared in group a. Labeled terminals of fastigial fibers were also found in group a. When the effective site included a region ventral to the oculomotor region, labeled P cells appeared in vermal lobules VIII and IX and labeled IO neurons appeared in caudal parts of a and b, in addition to group c. HRP injection into the posterior interposed nucleus (PIN) resulted in labeling of P cells in the paravermal zone and of IO neurons in the rostral two-thirds of the MAO and the dorsal accessory olive (DAO). The location of the labeled terminals coincided with the region where the densest labeling of IO neurons was found. Thus, the olivary projections to both the cerebellar cortex and deep cerebellar nuclei and the nucleoolivary projection exhibited a closely related topographical organization.

Saccadic eye movements evoked by microstimulation of the fastigial nucleus of macaque monkeys

1. Systematic exploration throughout the deep cerebellar nuclei and white matter disclosed that the region from which saccadic eye movements (saccades) were evoked with weak currents (less than 10 microA) was confined to the fastigial nucleus and the adjacent white matter. 2. When an electrode for stimulation was advanced in the cerebellum, saccades were evoked in the direction of the stimulated side (ipsilateral saccades) as it entered the low-threshold region. In some tracks, particularly when the electrode was advanced in the medial portion of the fastigial nucleus, the direction of the evoked saccades changed from the ipsilateral to the contralateral. 3. The mappings with microstimulation disclosed that the ipsilateral saccades were elicited from a relatively wide region that included almost the full extent of the fastigial nucleus. The low-threshold region continued in the white matter caudally into vermal lobule VII and rostrally into the dorsal aspect of the brachium conjunctivum. On the other hand, the contralateral saccades were evoked from a relatively circumscribed region in the ventromedial portion of the fastigial nucleus. 4. The reversal in the direction of the horizontal component occurred always in a narrow zone in the core of the fastigial nucleus. The caudal part of this zone coincided with an ellipsoidal region where anterogradely labeled axons of the Purkinje cells terminated when HRP was injected into vermal lobule VII. 5. When bicuculline (0.2-1 microgram) was injected in the ellipsoidal region, the ipsilateral saccades evoked from the dorsocaudal aspect of the region were suppressed for several hours. On the other hand, the contralateral saccades evoked from the ventromedial portion of the fastigial nucleus were either unchanged or enhanced. 6. Because the ipsilateral saccades were suppressed by bicuculline, they were most probably evoked by stimulation of the presynaptic component of gamma-amino-butyric acid-(GABA) mediated synapses, namely the axons of Purkinje cells. 7. Because stimulation of the presynaptic component of the inhibitory synapses evoked ipsilateral saccades, activation of the postsynaptic component would evoke contralateral saccades. In fact, the distribution of the fastigial sites yielding contralateral saccades coincided with the course of axons of fastigial neurons arising in the ellipsoidal region. It is most likely, therefore, that the contralateral saccades were evoked by stimulation of fastigial neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Distribution of external cuneate nucleus afferents to the cerebellum: I. Notes on the projections from the main cuneate and other adjacent nuclei. An experimental study with radioactive tracers in the cat.

Transport of radioactive leucine was used to demonstrate cerebellar projections from the external cuneate nucleus (NCE) and from adjacent portions of the main cuneate nucleus (NC), of the spinal trigeminal nucleus (N.tr.sp.V) and of the vestibular nuclei. Projections from NCE and NC in part terminate over exclusive regions and in part overlap. After injections limited to NCE, labeling is found in all regions of the anterior lobe and lobule VI, in vermal lobules VII, VIII, and IX, and in medial regions of central folia of the paramedian lobule. Afferents from NC are observed in intermediate and lateral regions of lobules IV-VI, in lobules VIII and IX, in medial portions of crura I and II, and in lateral parts of central folia of the paramedian lobule as well as in its rostral folia. Afferents from N.tr.sp.V are distributed in lateral regions of lobules II-VI, in the rostral folium of lobule IX, in medial parts of crura I and II, and in rostral folia of the paramedian lobule. Afferents from the vestibular nuclei are present in vermal lobules VII, IX, and X and in the paramedian lobule. Projections from NCE are bilateral with ipsilateral predominance, whereas those from NC and N.tr.sp.V are ipsilateral. Projections from NCE are generally much denser than those from the other nuclei. Throughout the projection area, afferents from NCE are distributed in greater amounts in folia close to the medullary core and are much less dense near the surface. Afferents from the other nuclei do not show surface-to-depth density differences.

Projections to the basilar pontine nuclei from face sensory and motor regions of the cerebral cortex in the rat.

Orthograde axonal transport tracing methods were used to describe the projections to the basilar pontine nuclei (BPN) which arise within the face representation of motor or somatosensory cerebral cortex. Injections centered in motor face (MF) cortex resulted in the labeling of several corticopontine terminal fields which exhibit a rostrocaudal columnar arrangement within the ipsilateral BPN. The location of such terminal zones is consistent with the somatotopic pattern of termination previously described for limb sensorimotor cortices. In contrast, the projections from somatosensory face (SF) cortical regions largely terminate in BPN areas separate from those receiving either limb sensorimotor or MF inputs. Both MF and SF cortices also give rise to projections to the contralateral BPN; those from SF cortex are less extensive than those of MF origin. In addition to their relationship with limb sensorimotor corticopontine terminations, the MF projections to the BPN also seem to partially overlap the projection zones of the cerebellopontine system, particularly the regions projected upon by the lateral cerebellar nucleus. The SF projections, on the other hand, appear to terminate in BPN areas that also receive input from either the dorsal column nuclei or the spinal trigeminal complex. There is only minimal potential overlap between MF and SF projections in the BPN. With regard to the pontocerebellar system, the projections from MF cortex terminate among BPN neurons which project to the cerebellar hemispheres, particularly lobus simplex, crus I and crus II. The SF projections also overlap BPN neurons which project to the lateral hemispheres in addition to the paraflocculus and vermal lobules VII and IXa,b. Taken together these observations suggest that subsets of BPN neurons might exist such that some receive convergent inputs from systems whose function can generally be regarded as motor (sensorimotor cortex, cerebellopontine) while another population of BPN neurons might integrate signals from systems which transmit somatosensory information (dorsal column nuclei, spinal trigeminal).