Posterior Interpositus Nucleus Research Articles

Topographic organization in the cerebellar nuclei and inferior olive in relation to cerebellar hemispheric lobules in the mouse: Distinction between crus I and neighboring lobules.

The parallel closed-loop topographic connections between subareas of the inferior olive (IO), cerebellar cortex, and cerebellar nuclei (CN) define the fundamental modular organization of the cerebellum. The cortical modules or zones are organized into longitudinal zebrin stripes which are extended across transverse cerebellar lobules. However, how cerebellar lobules, which are related to the cerebellar functional localization, are incorporated into the olivo-cortico-nuclear topographic organization has not been fully clarified. In the present study, we analyzed the lobular topography in the CN and IO by making 57 small bidirectional tracer injections in the lateral zebrin-positive stripes equivalent with C2, D1, and D2 zones in every hemispheric lobule in zebrin stripe-visualized mice. C2, D1, and D2 zones were connected to the lateral part of the posterior interpositus nucleus (lPIN), and caudal and rostral parts of the lateral nucleus (cLN, rLN), respectively, and from the rostral part of the medial accessory olive (rMAO), and ventral and dorsal lamellas of the PO (vPO, dPO), respectively, as reported. Within these areas, crus I was specifically connected to the ventral parts of the lPIN, cLN, and rLN, and from the rostrolateral part of the rMAO and the lateral parts of the vPO and dPO. The results indicated that the cerebellar modules have lobule-related subdivisions and that crus I is topographically distinct from other lobules. We speculate that crus I and crus I-connected subdivisions in the CN and IO are involved more in nonmotor functions than other neighboring areas in the mouse.

New Cerebello-Cortical Pathway Involved in Higher-Order Oculomotor Control.

The cerebellum and the basal ganglia play an important role in the control of voluntary eye movement associated with complex behavior, but little is known about how cerebellar projections project to cortical eye movement areas. Here we used retrograde transneuronal transport of rabies virus to identify neurons in the cerebellar nuclei that project via the thalamus to supplementary eye field (SEF) of the frontal cortex of macaques. After rabies injections into the SEF, many neurons in the restricted region, the ventral aspects of the dentate nucleus (DN), the caudal pole of the DN, and the posterior interpositus nucleus (PIN) were labeled disynaptically via the thalamus, whereas no neuron labeling was found in the anterior interpositus nucleus (AIN). The distribution of the labeled neurons was dorsoventrally different from that of DN and PIN neurons labeled from the motor cortex. In the basal ganglia, a large number of labeled neurons were confined to the dorsomedial portion of the internal segment of the globus pallidus (GPi) as more neurons were labeled in the inner portion of the GPi (GPii) than in the outer portion of the GPi (GPio). This is the first evidence of a projection between cerebellum/basal ganglia and the SEF that could enable the cerebellum to modulate the cognitive control of voluntary eye movement.

Quantitative organization of the excitatory synapses of the primate cerebellar nuclei: further evidence for a specialized architecture underlying the primate cerebellum

The cerebellar intrinsic connectivity is of remarkable regularity with a similar build repeated many times over. However, several modifications of this basic circuitry occur that can provide important clues to evolutionary adaptations. We have observed differences in the wiring of the cerebellar output structures (the deep cerebellar nuclei, DCN) with higher dendritic length density in the phylogenetically newer DCN. In rats, we showed that an increase in wiring is associated with an increase in the presynaptic vesicular glutamate transporter 1 (vGluT1). In this study, we have extended our analysis to the rhesus monkey and can show similarities and differences between the two species. The similarities confirm a higher density in vGluT1+ boutons in the lateral (LN/dentate) and posterior interpositus nucleus compared to the phylogenetically older DCN. In general, we also observe a lower density of vGluT1 and 2+ boutons in the monkey, which however, yields a similar number of excitatory boutons per neuron in both species. The only exception is the vGlut1+ boutons in the macaque LN/dentate, which showed a significantly lower number of vGluT1+ boutons per neuron. We also detected a higher percentage of co-labelled vGluT1 and 2 boutons in the macaque than we found in the rat. In summary, these results confirm that the hyposcalled dendrites of the monkey LN/dentate also show a lower number of vGluT1+ boutons per neuron. These results provide further support of our model relating the dendritic morphology of the LN/dentate neurons to the morphology of the specially enlarged LN/dentate nucleus in primates.

Cerebellar projections to the ventral lateral geniculate nucleus and the thalamic reticular nucleus in the cat.

The ventral lateral geniculate nucleus (LGNv) is a retinorecipient part of the ventral thalamus and in cats, it consists of medial (M), medial intermediate (IM), lateral intermediate (IL), lateral (L), and dorsal (D) subdivisions. These subdivisions can be differentiated not only by their cytoarchitecture, but also by their connectivity and putative functions. The LGNv may play a role in visuomotor gating, in that there is evidence of cerebellar afferent projections to the intermediate subdivisions. The cerebellar posterior interpositus (IP) and lateral (LC) nuclei are known to project to IM and IL, but the specifics of these projections are unclear. We hypothesized that the IP and LC project differentially to IM and IL. To evaluate LGNv innervation by the deep cerebellar nuclei, we injected the tract-tracer wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into several different regions of the LGNv and cerebellar nuclei of adult cats in either sex. Small injections into the middle and posterior LGNv retrogradely labeled cells in the ventral part of the IP. However, injections in the anterior regions of the LGNv, with or without diffusion into the thalamic reticular nucleus (Re), retrogradely labeled cells in the ventral part of both the IP and the LC. Confirmatory injections into the IP and LC produced terminal-like labeling distributed in IM, IL, and Re; injections mostly localized to the LC resulted in labeling mainly in IM and Re. We concluded that the IP projects to IL whereas the LC projects to IM and Re.

Anatomical evidence for the involvement of medial cerebellar output from the interpositus nuclei in cognitive functions

Although the cerebellar interpositus nuclei are known to be involved in cognitive functions, such as associative motor learning, no anatomical evidence has been available for this issue. Here we used retrograde transneuronal transport of rabies virus to identify neurons in the cerebellar nuclei that project via the thalamus to area 46 of the prefrontal cortex of macaques in comparison with the projections to the primary motor cortex (M1). After rabies injections into area 46, many neurons in the restricted region of the posterior interpositus nucleus (PIN) were labeled disynaptically via the thalamus, whereas no neuron labeling was found in the anterior interpositus nucleus (AIN). The distribution of the labeled neurons was dorsoventrally different from that of PIN neurons labeled from the M1. This defines an anatomical substrate for the contribution of medial cerebellar output to cognitive functions. Like the dentate nucleus, the PIN has dual motor and cognitive channels, whereas the AIN has a motor channel only.

Noradrenergic Control of Neuronal Firing in Cerebellar Nuclei: Modulation of GABA Responses

The effects of noradrenaline (NA) on inhibitory responses to gamma aminobutyric acid (GABA) in neurones of the deep cerebellar nuclei were studied in vivo in rats, using extracellular single-unit recordings and microiontophoretic drug application. NA application altered GABA-evoked responses in 95% of the neurones tested, but the effects differed between nuclei. Application of NA depressed GABA responses in the medial (MN) and posterior interpositus (PIN) nuclei, but enhanced GABA responses in the anterior interpositus nucleus (AIN). Comparable proportions of enhancing (57%) and depressive (43%) effects were found in the lateral nucleus (LN). The alpha2 noradrenergic receptor agonist clonidine mimicked the depressive effect of NA on GABA responses in MN and PIN and its enhancing effects in AIN and LN, while the alpha2 antagonist yohimbine partially blocked these effects. The beta-adrenergic agonist isoproterenol and antagonist timolol respectively induced and partially blocked enhancements of GABA responses in all nuclei except for LN, where isoproterenol had a weak depressive effect. It is concluded that NA modulates GABA responses by acting on both alpha2 and beta receptors. Activation of these receptors appears to be synergistic in the AIN and opposite in the remaining deep nuclei. These results support the hypothesis that the noradrenergic system participates in all the regulatory functions involving the cerebellum in a specific and differential manner, and suggest that any change in NA content, as commonly observed in ageing or stress, could influence cerebellar activity.

The Cerebellum and Cerebello-Thalamo-Cortical Channels Contribute to New Learning and Long-Term Memory of Motor Skill

Lu and his research team used the retrograde transneuronal transport of rabies virus to identify neurons in the cerebellar nuclei that project via the thalamus to the cerebral cortex of macaques. In particular, projections from deep cerebellar nuclei to area 46 of the prefrontal cortex were compared with projections to the primary motor cortex (M1). They found that, after viral injections into area 46, many labeled neurons were observed in the ventral aspect of the Posterior Interpositus Nucleus (PIN), whereas no neuron labeling was found in the Anterior Interpositus Nucleus (AIN). In contrast, a number of labeled neurons were found in the dorsal portion of the PIN after viral injections into the M1. Additionally, neurons labeled from the M1 injections were also observed in the AIN [1-3]. These findings demonstrate that the cerebellar interpositus nuclei possess distinct outputs to the prefrontal cortex versus the M1, which potentially contribute to different aspects of behavioral functions such as different stages of the motor learning. Medial cerebellar outputs from the interpositus nuclei have been thought to be crucial for the associative motor learning. McCormick and Thompson have reported that lesions of the interpositus nuclei abolished the memorized eyeblink response; recordings from these nuclei have revealed neuronal activity to response learning [4]. Yet, clinical studies have reported that initial stage of trace eyeblink conditioning learning was impaired in patients with lesions in the PIN [5]. Imaging studies have also shown that the cerebellum play a key role in eyeblink conditioning [6-8]. Moreover, significant changes of positron emission tomography and regional cerebral blood flow in several areas, including the cerebellum and the prefrontal cortex, were observed during performance of associative motor learning task [9]. The above, taken together with the new medial cerebellar channels from the posterior interpositus nucleus to area 46 of the prefrontal cortex, it is reasonable to hypothesize that the cerebellum and cerebello-thalamocortical channels contribute to motor learning. The medial cerebellar output from the ventral PIN and the dorsal PIN/AIN play differential roles in various steps of the motor learning [5,10,11]. The dorsal aspect of the PIN has been thought to contribute to performance of memorized motor responses such as eyeblink and saccadic eye movements rather than to their initial learning [10, 11]. If this is the case, then impairment in the acquisition of the new learning by lesions of the PIN could be due to functional blockade of the ventral rather than dorsal portion of the PIN [5]. Furthermore, previous studies have shown evidence that the expression of representative motor memory formation genes was increased selectively in the AIN, but not in the PIN [12]. This finding strongly suggests that the AIN is involved in the storage and/or retrieval of long-term memory of motor learning. Moreover, many studies have indicated that the AIN is the site for long-term memory rather than new learning during practice of the eyeblink conditioning response. Examples include lesion [13-17]; inactivation [18,19]; electron microscopy [20]; functional magnetic resonance imaging [21]. Given the above, it is natural to raise a theory that the medial cerebellar output from the ventral PIN and the dorsal PIN/AIN plays a critical role in the new learning and long-term memory, respectively, during the motor learning processing. Interestingly, different cortical areas have been thought to be involved in these various steps of motor learning. A considerable theory for motor learning indicates that new learning is an explicit process originating in the prefrontal cortex, and that the long term memory for the learned motor skill becomes automatic and an implicit process formed in the motor cortex [22-24]. Thus, the disynaptic pathway from the ventral aspect of the PIN to area 46 may be involved in the initiation of the association of motor learning. After repeated practice, cerebellar channels to the M1 originating from the dorsal PIN/AIN turn to play a key role in the storage and/or retrieval of long-term memory, which makes the association automatic. Last, neuropsychological testing of patients with cerebellar lesions has revealed specific deficits in different faculties, including visual perception [25-31], short-term memory [32,33], or verbal fluency [34]. Moreover, clinical studies have shown that, in the brains of subjects with autism, the most consistent abnormalities are found in cerebellar Purkinje cells [35]. Accordingly, the questions of whether and how these cerebello-thalamo-cortical channels and their involvements in

Glucocorticoid receptor blockade in the posterior interpositus nucleus reverses maternal separation-induced deficits in adult eyeblink conditioning

Previously, we showed that neonatal maternal separation impaired eyeblink conditioning in adult rats. This impairment is correlated with increased glucocorticoid receptor (GR) expression in the cerebellar posterior interpositus nucleus, a critical site of learning-related plasticity. To assess whether increased GR expression is responsible for the separation-induced learning impairment, we infused a GR antagonist (mifepristone) or vehicle into the posterior interpositus during eyeblink conditioning in adult male Long-Evans rats that had undergone control rearing or neonatal maternal separation (1 h/day, postnatal days 2–14). Rats received standard rearing (control) or neonatal maternal separation (separated; 1 h/day on postnatal days 2–14). In adulthood, rats underwent surgery for implantation of recording electrodes in the orbicularis oculi of the left eyelid, a bipolar stimulating electrode dorsocaudal to the left eye, and an infusion guide cannula positioned over the posterior interpositus. Then, rats underwent 10 daily sessions of eyeblink conditioning. Rats in each group received either 0.2 μl of mifepristone (2 ng in 2% EtOH) or vehicle infusion prior to each eyeblink conditioning session. Mifepristone infusions improved conditioning in separated rats, but impaired control rats’ performance. Thus, separation-induced increases in GRs may mediate the learning deficit seen in adult neonatally separated rats.

Cetacean Brain Evolution: Dwarf Sperm Whale (Kogia sima) and Common Dolphin (Delphinus delphis) – An Investigation with High-Resolution 3D MRI

This study compares a whole brain of the dwarf sperm whale (Kogia sima) with that of a common dolphin (Delphinus delphis) using high-resolution magnetic resonance imaging (MRI). The Kogia brain was scanned with a Siemens Trio Magnetic Resonance scanner in the three main planes. As in the common dolphin and other marine odontocetes, the brain of the dwarf sperm whale is large, with the telencephalic hemispheres remarkably dominating the brain stem. The neocortex is voluminous and the cortical grey matter thin but expansive and densely convoluted. The corpus callosum is thin and the anterior commissure hard to detect whereas the posterior commissure is well-developed. There is consistency as to the lack of telencephalic structures (olfactory bulb and peduncle, olfactory ventricular recess) and neither an occipital lobe of the telencephalic hemisphere nor the posterior horn of the lateral ventricle are present. A pineal organ could not be detected in Kogia. Both species show a tiny hippocampus and thin fornix and the mammillary body is very small whereas other structures of the limbic system are well-developed. The brain stem is thick and underlies a large cerebellum, both of which, however, are smaller in Kogia. The vestibular system is markedly reduced with the exception of the lateral (Deiters’) nucleus. The visual system, although well-developed in both species, is exceeded by the impressive absolute and relative size of the auditory system. The brainstem and cerebellum comprise a series of structures (elliptic nucleus, medial accessory inferior olive, paraflocculus and posterior interpositus nucleus) showing characteristic odontocete dimensions and size correlations. All these structures seem to serve the auditory system with respect to echolocation, communication, and navigation.

Neonatal maternal separation-induced changes in glucocorticoid receptor expression in posterior interpositus interneurons but not projection neurons predict deficits in adult eyeblink conditioning

Neonatal maternal separation impairs adult eyeblink conditioning. This impairment is correlated with increases in adult glucocorticoid receptor (GR) expression in the posterior interpositus nucleus [A.A. Wilber, C. Southwood, G. Sokoloff, J.E. Steinmetz, C.L. Wellman, Neonatal maternal separation alters adult eyeblink conditioning and glucocorticoid receptor expression in the interpositus nucleus of the cerebellum, Developmental Neurobiology 67 (2007) 1751–1764], a key structure in the neural circuitry controlling eyeblink conditioning. To further localize this effect, we assessed adult eyeblink conditioning and GR expression in projection versus interneurons in the interpositus of rats that had undergone standard rearing or maternal separation (1 h/day) on postnatal days 2–14. At 3 months of age, interpositus neurons were labeled with the retrograde tracer biotinylated dextran amine (BDA). After delay eyeblink conditioning, brains were processed immunohistochemically for GR and BDA labeling of interpositus neurons. GR expression was quantified in BDA-labeled and unlabeled neurons. Neonatal maternal separation impaired adult eyeblink conditioning. Control rats had significantly less GR expression in posterior interpositus BDA-unlabeled versus BDA-labeled neurons, but this difference was absent in maternally separated rats. While neonatal separation significantly increased GR expression in BDA-labeled and unlabeled posterior interpositus neurons, only GR expression in non-BDA-labeled neurons was associated with eyeblink conditioning. Thus, neonatal maternal separation may alter interneuronal modulation of interpositus output neurons, producing deficits in adult eyeblink conditioning.

Topographic distribution of output neurons in cerebellar nuclei and cortex to somatotopic map of primary motor cortex

To investigate the somatotopic organization of the cerebellum, we analysed multisynaptic inputs to the primary motor cortex (MI) using retrograde transneuronal transport of rabies virus. At 3 days after rabies injections into proximal forelimb, distal forelimb and hindlimb representations of the macaque MI, second-order neurons via the thalamus were labeled in the deep cerebellar nuclei, including the dentate (DN), anterior interpositus (AIN) and posterior interpositus nuclei. In the DN, the labeling of both the forelimb and hindlimb was seen mainly in the dorsal aspect. The labeling of the hindlimb was located rostral to that of the forelimb and the labeling of the proximal forelimb was located slightly rostral to that of the distal forelimb. The same rostrocaudal arrangement was observed in the AIN. In the posterior interpositus nucleus, however, labeling from the MI hindlimb and forelimb representations largely overlapped. At the 4-day postinjection period, third-order labeling occurred in Purkinje cells of the cerebellar hemisphere. The Purkinje cell labeling from the forelimb representation, including the proximal and distal regions, was observed primarily in lobules IV-VI and crus I. The proximal forelimb labeling was both rostral and lateral to that of the distal forelimb within lobules IV-VI. However, the hindlimb labeling was seen both rostral and lateral to that of the proximal forelimb within lobules III-VI. These results indicate that the hindlimb, proximal forelimb and distal forelimb are arranged rostrocaudally in the DN and AIN, whereas there is dual somatotopy along the rostrocaudal and lateromedial axes in the cerebellar cortex.

Extracellular amino acid levels in the interpositus nucleus during classical eyeblink conditioning in alert cats.

The extracellular levels of selected amino acids in the cerebellar posterior interpositus nucleus (PIN) during classical eyeblink conditioning was analyzed in alert cats using a delay paradigm. Animals were prepared for the chronic recording of eyelid movements (with the magnetic search-coil technique) and the electromyographic activity of the orbicularis oculi muscle. With the help of a guide and push-pull cannulae, selected PIN sites were perfused daily during classical eyeblink conditioning. The perfusate was sampled at intervals of 5 min and analyzed with a high-pressure liquid chromatography- electrochemical detection (HPLC-EC) method. The analysis of push-pull perfusate revealed a significant increase in the release of glycine, taurine, and glutamate across the successive conditioning sessions, in parallel with the acquisition of eyelid conditioned responses (CRs). Both CRs and extracellular levels of these three amino acids returned to control values during extinction. Other amino acids (alanine, GABA, glutamine, serine, and threonine) did not undergo modifications in their extracellular concentrations across the training. Results are discussed with regard to the role of PIN in this type of associative learning.

Olivo-cortico-nuclear localizations within crus I of the cerebellum

Retrograde and anterograde tracers were microinjected into the folia of crus I of the cat cerebellum to investigate spatial localization in olivo-cerebellar and cortico-nuclear projections. The folia were shown to be mainly occupied in rostrocaudal succession by three zones receiving their olivo-cerebellar climbing fiber afferents from parts of, respectively, the dorsal lamella of the principal olive, the ventral lamella of the principal olive, and the rostral half of the medial accessory olive. These zones are presumably parts of the D(2), D(1), and C(2) cerebellar cortical zones, as earlier proposed by Rosina and Provini ([1982] Neuroscience 7:2657-2676). Their respective nuclear target territories were found to be in the rostroventral quadrant of nucleus lateralis, the caudoventral quadrant of nucleus lateralis, and the ventral half of nucleus interpositus posterior. The medial-to-lateral width of each zone was shown to be innervated by different groups of olive cells and to project respectively to medial and lateral parts of the nuclear territory for that zone, consistent with the existence in crus I of olivo-cortico-nuclear microcomplexes (cf. Ito [1984] New York: Raven Press). Parts of the length of each zone located within different folia were also shown to relate to different groups of olive cells and to different regions of the zone's overall nuclear territory. Interfolial localizations, which were heavily overlapping in nature, intersected orthogonally with those for zone width. The fine-grain topography implies that individual microzones exist within each of the zones present within crus I. The results also have implications for the possibility that lateral cerebellar pathways are involved in cognition.

Role of cerebellar interpositus nucleus in the genesis and control of reflex and conditioned eyelid responses.

The role of cerebellar circuits in the acquisition of new motor abilities is still a matter of intensive debate. To establish the contribution of posterior interpositus nucleus (PIN) to the performance and/or acquisition of reflex and classically conditioned responses (CRs) of the eyelid, the effects of microstimulation and/or pharmacological inhibition by muscimol of the nucleus were investigated in conscious cats. Microstimulation of the PIN in naive animals evoked ramp-like eyelid responses with a wavy appearance, without producing any noticeable plastic functional change in the cerebellar and brainstem circuits involved. Muscimol microinjections decreased the amplitude of reflex eyeblinks evoked by air puffs, both when presented alone or when paired with a tone as conditioned stimulus (CS). In half-conditioned animals, muscimol injections also decreased the amplitude and damped the typical wavy profile of CRs, whereas microstimulation of the same sites increased both parameters. However, neither muscimol injections nor microstimulation modified the expected percentage of CRs, suggesting a major role of the PIN in the performance of eyelid responses rather than in the learning process. Moreover, the simultaneous presentation of CS and microstimulation in well trained animals evoked CRs similar in amplitude to the added value of those evoked by the two stimuli presented separately. In contrast, muscimol-injected animals developed CRs to paired CS and microstimulation presentations, larger than those evoked by the two stimuli when presented alone. It is concluded that the PIN contributes to the enhancement of both reflex and conditioned eyelid responses and to the damping of resonant properties of neuromuscular elements controlling eyelid kinematics.

Extracellular Amino Acid Levels in the Posterior Interpositus Nucleus during Eyelid Conditioned Responses in Cats

Extracellular Amino Acid Levels in the Posterior Interpositus Nucleus during Eyelid Conditioned Responses in Cats

An Experimental Study of Posterior Interpositus Involvement in the Genesis and Control of Conditioned Eyelid Responses

The participation of the rostral-dorsal part of the posterior interpositus nucleus in the genesis of classically-conditioned eyelid responses in alert cats was studied. Cats were prepared for the recording of left eyelid movements with the search-coil-in-a-magnetic-field technique and of the electromyographic activity of the orbicularis oculi muscle. A stimulating electrode was implanted in the contralateral red nucleus and a guide cannula in the ipsilateral interpositus. The cannula allowed unitary recordings, electrical microstimulation, drug injection, and push-pull perfusion of the selected interpositus site. Perfusate was used for amino acid analysis with an HPLC-EC method. Animals were conditioned with a delay (CS: tone, US: air puff) paradigm. Antidromically identified interpositus neurons fired during eyelid conditioned responses (CRs) with a variable delay to CR start. Some neurons (type A) increased and other (type B) decreased their firing during CR performance. Electrical microstimulation of posterior interpositus was able to increase CR amplitude when applied during CS presentation. Muscimol decreased CR amplitude in well-trained animals. The analysis of push-pull perfusate showed a significant increase in glutamate, glycine, and taurine, but not GABA levels, during conditioning in comparison with habituation and extinction periods. Results indicate an involvement of the rostral-dorsal part of the posterior interpositus nucleus in the genesis of eyelid conditioned responses, playing an enhancing or controlling role in CR performance, rather than being its initiator.

Uncrossed and crossed projections from the upper cervical spinal cord to the cerebellar nuclei in the rat, studied by anterograde axonal tracing.

In the upper cervical spinal segments, neurons in the medial part of lamina VI give rise to uncrossed spinocerebellar axons, whereas the central cervical nucleus (CCN) and neurons in laminae VII and VIII give rise to crossed spinocerebellar axons. Using anterograde labeling with biotinylated dextran in the rat, we examined the projections of these neuronal groups to the cerebellar nuclei. Uncrossed and crossed projections were distinguished by cerebellar lesions placed on the side contralateral or ipsilateral to the tracer injections confined to the second and third cervical spinal segments (C2 and C3, respectively). Labeled terminals of uncrossed projections were seen in the middle, dorsal, and ventrolateral parts of the middle subdivision and in the ventral part of the caudomedial subdivision of the medial nucleus. In the anterior interpositus nucleus, terminals were seen in the middle of the mediolateral extent, whereas, in the posterior interpositus nucleus, they were seen in lateral and caudal parts. The terminals of crossed projections from the CCN were distributed ventrally in medial to ventrolateral parts of the middle subdivision of the medial nucleus. Some terminals were seen in the caudomedial subdivision of the medial nucleus. In the anterior interpositus nucleus, labeled terminals were seen mainly in rostromedial parts, whereas, in the posterior interpositus nucleus, they were seen in caudal and dorsal parts of the medial half. The present study suggests that the medial lamina VI group and the CCN in the upper cervical segments project to the different areas of the cerebellar nuclei and are concerned with different functions.

Cerebellar posterior interpositus nucleus as an enhancer of classically conditioned eyelid responses in alert cats.

Cerebellar posterior interpositus neurons were recorded in cats during delayed and trace conditioning of eyeblinks. Type A neurons increased their firing in the time interval between conditioned and unconditioned stimulus presentations for both paradigms, while type B neurons decreased it. The discharge of different type A neurons recorded across successive conditioning sessions increased, with slopes of 0.061-0.078 spikes/s/trial. Both types of neurons modified their firing several trials in advance of the appearance of eyelid conditioned responses, but for each conditioned stimulus presentation their response started after conditioned response onset. Interpositus microstimulation evoked eyelid responses similar in amplitude and profiles to conditioned responses, and microinjection of muscimol decreased conditioned response amplitude. It is proposed that the interpositus nucleus is an enhancer, but not the initiator, of eyelid conditioned responses.

Role of the Cerebellar Posterior Interpositus Nucleus in Saccades I. Effect of Temporary Lesions

The ventrolateral corner of the cerebellar posterior interpositus nucleus (VPIN) contains many neurons that respond during saccades. To characterize the VPIN contribution to saccades, I located this area in three monkeys with single-unit recording and injected the GABA(A) agonist muscimol among saccade-related neurons there to reduce or eliminate neural activity. I compared the size, direction, velocity, and duration of saccades recorded before and after a unilateral injection in all three monkeys. In two of three monkeys, I also examined saccades after bilateral injection. After unilateral VPIN inactivation, upward saccades were abnormally large (avg. across all 3 monkeys = 112% of normal) and downward saccades were abnormally small (avg. across all 3 monkeys = 94% of normal). In the two monkeys tested, bilateral inactivation increased these abnormalities. Upward saccades went from 111% of normal size in these two monkeys after unilateral inactivation to 120% after bilateral inactivation; downward saccades went from 97 to 86%. VPIN inactivation caused changes in saccade gain and did not add of a constant offset to saccades. (The 1 exception was upward saccades in 1 monkey in which both gain and offset changed.) Neither uni- nor bilateral VPIN inactivation consistently affected the size of horizontal saccades (uni- avg. = 101% normal; bi- avg. = 97% normal). In two of the three monkeys, saccades to horizontal targets angled significantly upward after VPIN inactivation (uni- avg. = 3.6 degrees above normal, bi- avg. = 10.3 degrees above normal). The velocities of horizontal saccades were not strongly affected, but downward saccades exhibited abnormally low peak velocities and long durations. Upward velocities were inconsistently changed. I interpret these results to mean that the activity of some VPIN neurons helps drive the eyes downward and the activity of others helps drive the eyes upward. The downward drive outweighs the upward drive. The net effect of VPIN inactivation is to deprive all saccades of a downward component and to slow downward saccades.

Differential effects of deep cerebellar nuclei inactivation on reaching and adaptive control.

This study examined the effects of selective inactivation of the cerebellar nuclei in the cat on the control of multijoint trajectories and trajectory adaptation to avoid obstacles. Animals were restrained in a hammock and trained to perform a prehension task in which they reached to grasp a small cube of meat from a narrow food well. To examine trajectory adaptation, reaching was obstructed by placing a horizontal bar in the limb's path. Inactivation was produced by microinjection of the GABA agonist muscimol (0.25-1.0 microg in 1 microL saline). Fastigial nucleus inactivation produced a severe impairment in balance and in head and trunk control but no effect on reaching and grasping. Dentate inactivation slowed movements significantly and produced a significant increase in tip path curvature but did not impair reaching and grasping. Selective inactivation of the anterior and posterior interpositus nuclei did not impair grasping but severely decreased the accuracy of reaching movements and produced different biases in wrist and paw paths. Anterior interpositus inactivation produced movement slowing (wrist speed) and under-reaching to the food well. Wrist and tip paths showed anterior biases and became more curved. Also animals could no longer make anticipatory adjustments in limb kinematics to avoid obstructions but sensory-evoked corrective responses were preserved. Posterior interpositus inactivation produced a significant increase in wrist speed and overreaching. Wrist and tip paths showed a posterior bias and became more curved, although in a different way than during anterior interpositus inactivation. Posterior interpositus inactivation did not impair trajectory adaptation to reach over the obstacle. During inactivation of either interpositus nucleus, all measures of kinematic temporal and spatial variability increased with somewhat greater effects being produced by anterior interpositus inactivation. We discuss our results in relation to the hypothesis that anterior and posterior interpositus have different roles in trajectory control, related possibly to feed-forward use of cutaneous and proprioceptive inputs, respectively. The loss of adaptive reprogramming during anterior interpositus inactivation further suggests a role in motor learning. Comparison with results from our earlier motor cortical study shows that the distinctive impairments produced by inactivation of these two nuclei are similar to those produced by selective inactivation of different zones in the forelimb area of rostral motor cortex. Our findings are consistent with the hypothesis that there are separate functional output channels from the anterior and posterior interpositus nuclei to rostral motor cortex for distinct aspects of trajectory control and, from anterior interpositus alone, for trajectory adaptation.