Cerebellum is known as a center for sensory/motor coordination and memory storage in motor learning. The vestibular nuclei have extensive afferent and efferent connections with posterior cerebellum which can be referred to as vestibulocerebellum. While secondary vestibular afferents are distributed bilaterally in the vestibulocerebellum, primary afferents may directly project to ipsilateral vestibulocerebellum. The Purkinje cells which are the only output neurons from the cerebellar cortex receive vestibular information via parallel and climbing fibers. That information is integrated and encoded in the Purkinje cells and then conveyed into the vestibular nucleus or deep cerebellar nucleus, which permits adaptive guidance of vestibular function by the vestibulocerebellum.
Cerebellar Cortex ; Cerebellar Nuclei ; Cerebellum ; Electrophysiology ; Learning ; Membranes ; Memory ; Neurons ; Patch-Clamp Techniques ; Purkinje Cells ; Vestibular Nuclei

What is memory? How does the brain process the sensory information and modify an organism's behavior? Many neuroscientists have focused on the activity- and experience-dependent modifications of synaptic functions in order to solve these fundamental questions in neuroscience. Recently, the plasticity of intrinsic excitability (called intrinsic plasticity) has emerged as an important element for information processing and storage in the brain. As the cerebellar Purkinje cells are the sole output neurons in the cerebellar cortex and the information is conveyed from a neuron to its relay neurons by forms of action potential firing, the modulation of the intrinsic firing activity may play a critical role in the cerebellar learning. Many voltage-gated and/or Ca²⁺-activated ion channels are involved in shaping the spiking output as well as integrating synaptic inputs to finely tune the cerebellar output. Recent studies suggested that the modulation of the intrinsic excitability and its plasticity in the cerebellar Purkinje cells might function as an integrator for information processing and memory formation. Moreover, the intrinsic plasticity might also determine the strength of connectivity to the sub-cortical areas such as deep cerebellar nuclei and vestibular nuclei to trigger the consolidation of the cerebellar-dependent memory by transferring the information.
Action Potentials ; Automatic Data Processing ; Brain ; Cerebellar Cortex ; Cerebellar Nuclei ; Cerebellum ; Fires ; Ion Channels ; Learning* ; Memory ; Neuronal Plasticity ; Neurons ; Neurosciences ; Plastics* ; Purkinje Cells* ; Vestibular Nuclei

The pogo mouse is a new ataxic mutant derived from a Korean wild mouse. The pogo mutation is inherited as an autosomal recessive trait on chromosome 8. Mutations in gene coding for the alpha(1A)subunit of voltagegated P/Q-type Ca(2+) channel have been shown to cause phenotypes in humans and mice, i.e., tottering, leaner, rolling mouse mouse Nagoya. Using immunohistochemistry, the expression of the alpha(1A)subunit of voltage-gated P/Q-type Ca(2+) channel was examined in pogo mice cerebellum including deep cerebellar nuclei (DCN). We observed alpha(1A)immunoreactivity in the cerebellar cortex (Purkinje cell and granule cell) and DCN of ataxic pogo mice and heterozygote control mice. There was no difference in cerebellar cortical alpha(1A)immunoreactivity between ataxic pogo mice and heterozygous littermate controls (pogo/+). However, we observed alpha(1A)immunoreactivity in the Purkinje cells of control and ataxic pogo mice cerebellum and DCN. We found a significant difference between pogo and heterozygous controls in terms of alpha(1A)immunoreactivities in the DCN. alpha(1A)immunoreactivity in this nucleus in pogo was much higher than in heterozygous littermate controls. No significant differences were observed in the interposed nucleus between pogo and heterozygous controls, but we found that the alpha(1A)subunits were clearer and more abundant in the lateral and medial regions of pogo than in control mice in these regions, where only weak immunoreactivity was observed. This elevated expression of the alpha(1A)subunit in deep cerebellar neurons of pogo might be a compensation for the altered function of P/Q type calcium channel and be related with the induction of the ataxic phenotype in pogo mice.
Animals ; Ataxia ; Calcium Channels* ; Calcium* ; Cerebellar Cortex ; Cerebellar Nuclei ; Cerebellum* ; Chromosomes, Human, Pair 8 ; Clinical Coding ; Compensation and Redress ; Heterozygote ; Humans ; Immunohistochemistry ; Mice* ; Neurons ; Phenotype ; Purkinje Cells

The purpose of this study is to identify the differences of zebrin II expression between ataxic pogo and normal Balb/C mouse cerebellum. Zebrin II is expressed by subsets of Purkinje cells that form an array of parasagittal bands that extend rostrocaudally throughout the cerebellar cortex, separated by similar bands of Purkinje cells that do not express zebrin II. Zebrin II immunoreactivity was localized in the perikarya of Purkinje cells, and the dendrites. Distribution of zebrin II-immunoreactive Purkinje cells were very similar pattern in pogo and Balb/C mouse cerebellum. But, in the lobule III, distribution of zebrin II expression was different between pogo and Balb/C mouse cerebellum. In lobule III of Balb/c mouse cerebellum, 10~15 zebrin II-immunoreactive Purkinje cells were observed and clustered to form a parasagittal bands. On the other hand, zebrin II expressions of lobule III in pogo mouse cerebellum showed a little different patterns. In lobule III of pogo mouse cerebellum, three bilateral zebrin II immunoreactive parasagittal band were observed. P1 band was almost same with lobule III of Balb/C mouse cerebellum. But, P2 bands were composed of 50~60 Purkinje cells which were immunoreactive with zebrin II. These kind of thickening in zebrin II expression of pogo mouse cerebellum may be due to the genetical difference. Furthermore, these results may provide useful information with further ataxic pogo mice cerebellum studies.
Animals ; Cerebellar Cortex ; Cerebellum* ; Dendrites ; Hand ; Immunohistochemistry ; Mice* ; Purkinje Cells

The cerebellum is conceptualized as a processor of complex movements and is also endowed with roles in cognitive and emotional behaviors. Although the axons of deep cerebellar nuclei are known to project to primary thalamic nuclei, macroscopic investigation of the characteristics of these projections, such as the spatial distribution of recipient zones, is lacking. Here, we studied the output of the cerebellar interposed nucleus (IpN) to the ventrolateral (VL) and centrolateral (CL) thalamic nuclei using electrophysiological recording in vivo and trans-synaptic viral tracing. We found that IpN stimulation induced mono-synaptic evoked potentials (EPs) in the VL but not the CL region. Furthermore, both the EPs induced by the IpN and the innervation of IpN projections displayed substantial heterogeneity across the VL region in three-dimensional space. These findings indicate that the recipient zones of IpN inputs vary between and within thalamic nuclei and may differentially control thalamo-cortical networks.
Axons ; Cerebellar Nuclei ; Cerebellum ; Thalamic Nuclei

There is growing evidence that alterations in Ca2+ homeostasis may play a role in processes of brain aging and neurodegeneration. However, few have focused on voltage-gated Ca2+ channel (VGCC) subunits, much less on expression of other voltage-gated ion channels, i.e. voltage-gated K+ (Kv) and Na+ (Nav) channels. In the present study, we have investigated the spatial patterning of VGCCs, Kv1 and Nav channels by immunohistochemistry. This study have shown clearly that the VGCCs, Kv1 and Nav channels have differential distribution in the cerebellum of gerbil, which is used as an ischemia and epilepsy animal model. Immunoreactivities for Cav2.1, Cav1.2 and Cav1.3 were observed in the cell bodies and dendritic branches of Purkinje cells. In particular, Cav1.3 immunoreactivity was most prominent in the cell bodies and dendritic arborizations. A distinct band of punctate immunoreactivity for the Cav2.1, Cav2.2, Cav1.2 and Cav1.3 were observed in cerebellar nuclei. Strong immunoreactivities for Kv1.3, Kv1.4, Kv1.5 and Kv1.6 were observed in the Purkinje cell bodies, whereas Kv1.2 immunoreactivity was found in the basket cell axon plexus and terminal regions around the Purkinje cells. In the cerebellar nuclei, Kv1.2, Kv1.4 and Kv1.6 proteins were clearly detected in the soma of cerebellar output neurons. The most intense staining for Nav1.1 was observed in the granular layer, whereas strong immunoreactivity for Nav1.2 were seen in the Purkinje cell bodies, and extended into their dendrites. The overall results have demonstrated the expression patterns of VGCCs, Kv1 and Nav channels in gerbil cerebellum. Further studies are needed to define changes in other Ca2+ channel types to determine whether any channel changes represent selective loss of specific receptors or of cell loss, and to determine whether changes in Kv and Nav channels are linked to Ca2+ channel changes.
Aging ; Axons ; Brain ; Carisoprodol ; Cerebellar Nuclei ; Cerebellum* ; Dendrites ; Epilepsy ; Gerbillinae* ; Homeostasis ; Immunohistochemistry ; Ion Channels* ; Ischemia ; Models, Animal ; Neurons ; Purkinje Cells

Channels formed by the transient receptor potential (TRP) family of proteins have a variety of physiological functions. In the present study, we examined the localization of canonical transient receptor potential channels (TRPCs) in rat cerebellum. Twelve adult (4~6 month old) Sprague-Dawley rats were examined in this study. We performed immunohistochemistry using specific antibodies against TRPCs to investigate the detailed and comparative distribution of six TRPCs in rat cerebellum. There was a high density of TRPC1, TRPC3, TRPC4, TRPC5 and TRPC7, with a much lower density of TRPC6 in the rat cerebellar cortex. The somatodendritic Purkinje cell areas were intensely stained with antiTRPC3, TRPC4, TRPC5 or TRPC7 antibodies, whereas the staining intensity of TRPC6 was relatively low in the Purkinje cell bodies. In the cerebellar nuclei, the cell bodies of cerebellar output neurons showed moderate TRPC1, TRPC3, TRPC5 and TRPC7 immunoreactivities, while TRPC6 immunoreactivity was observed in the surrounding neuropil. This study showing the differential localizations of TRPC channels in the cerebellum may provide useful data for the future investigations on the structural and functional properties of TRPCs.
Adult ; Animals ; Antibodies ; Cerebellar Cortex ; Cerebellar Nuclei ; Cerebellum ; Humans ; Immunohistochemistry ; Neurons ; Neuropil ; Proteins ; Rats ; Rats, Sprague-Dawley ; Transient Receptor Potential Channels

It is well known that small heat shock proteins play a role as molecular chaperone. However, during normal development of the cerebellum, expression and distribution of HSP27 and alphaB-crystallin (alphaBC) which are small heat shock proteins have not been reported. To verify the protective role of HSP27 and alphaBC in neurons and glial cells, we examined the expression and distribution of HSP27 and alphaBC in the developing chick cerebellum using immunoblot, immunohistochemical and double immunofluorescence staining. Expression of both HSP27 and alphaBC was first identified in the cerebellum of the embryonic day 14 (E14) embryo, and was increased at E18. Double immunofluorescence analysis with myelin-basic protein (MBP) demonstrated that alphaBC positive (+) cells were mature myelinating oligodendrocytes. alphaBC+ cells were observed in the white matter of the E14 cerebellum. At E18, there were a number of alphaBC+ cells in the white matter and a few cells in the granular layer of the gray matter. On the other hand, HSP27+ cells were observed in the white matter and the Purkinje cell layer at E14. At E18, HSP27+ signals were observed in Purkinje cells and neurons of cerebellar nucleus as well as oligodendrocytes in the white matter and the granular layer. The results that HSP27 and alphaBC were expressed in specific neurons and glial cells in the developing cerebellum suggest that HSP27 and alphaBC may be involved in the protective mechanism for the apoptosis of neurons and the physiological stress occurred in oligodendrocyts during cell maturation.
Apoptosis ; Cerebellar Nuclei ; Cerebellum* ; Embryonic Structures ; Fluorescent Antibody Technique ; Hand ; Heat-Shock Proteins, Small ; Molecular Chaperones ; Myelin Sheath ; Neuroglia ; Neurons ; Oligodendroglia ; Purkinje Cells ; Stress, Physiological

The deep cerebellar nuclei (DCN) integrate various inputs to the cerebellum and form the final cerebellar outputs critical for associative sensorimotor learning. However, the functional relevance of distinct neuronal subpopulations within the DCN remains poorly understood. Here, we examined a subpopulation of mouse DCN neurons whose axons specifically project to the ventromedial (Vm) thalamus (DCN^Vm neurons), and found that these neurons represent a specific subset of DCN units whose activity varies with trace eyeblink conditioning (tEBC), a classical associative sensorimotor learning task. Upon conditioning, the activity of DCN^Vm neurons signaled the performance of conditioned eyeblink responses (CRs). Optogenetic activation and inhibition of the DCN^Vm neurons in well-trained mice amplified and diminished the CRs, respectively. Chemogenetic manipulation of the DCN^Vm neurons had no effects on non-associative motor coordination. Furthermore, optogenetic activation of the DCN^Vm neurons caused rapid elevated firing activity in the cingulate cortex, a brain area critical for bridging the time gap between sensory stimuli and motor execution during tEBC. Together, our data highlights DCN^Vm neurons' function and delineates their kinematic parameters that modulate the strength of associative sensorimotor responses.
Animals ; Blinking ; Cerebellar Nuclei/physiology* ; Cerebellum ; Mice ; Neurons/physiology* ; Thalamus

The toxic effects of morphine sulfate in the adult cerebral cortex and one-day neonatal cerebellum have been studied. This study was carried out to evaluate the effect of maternal morphine exposure during gestational and lactation period on the Purkinje cells and cerebellar cortical layer in 18- and 32-day-old mice offspring. Thirty female mice were randomly allocated into cases and controls. In cases, animals received morphine sulfate (10 mg/kg/body weight intraperitoneally) during the 7 days before mating, gestational day (GD 0-21) 18 or 32. The controls received an equivalent volume of saline. The cerebellum of six infants for each group was removed and each was stained with cresyl violet. Quantitative computer-assisted morphometric study was done on cerebellar cortex. The linear Purkinje cell density in both experimental groups (postnatal day [P]18, 23.40+/-0.5; P32, 23.45+/-1.4) were significantly reduced in comparison with the control groups (P18, 28.70+/-0.9; P32, 28.95+/-0.4) (P<0.05). Purkinje cell area, perimeter and diameter at apex and depth of simple lobules in the experimental groups were significantly reduced compared to the controls (P<0.05). The thickness of the Purkinje layer of the cerebellar cortex was significantly reduced in morphine treated groups (P<0.05). This study reveals that morphine administration before pregnancy, during pregnancy and during the lactation period causes Purkinje cells loss and Purkinje cell size reduction in 18- and 32-day-old infant mice.
Adult ; Animals ; Benzoxazines ; Cell Count ; Cell Size ; Cerebellar Cortex ; Cerebellum ; Cerebral Cortex ; Female ; Humans ; Infant ; Lactation ; Mice ; Morphine ; Pregnancy ; Purkinje Cells ; Viola