scholarly journals Kv3.3b: a novel Shaw type potassium channel expressed in terminally differentiated cerebellar Purkinje cells and deep cerebellar nuclei

1994 ◽  
Vol 14 (2) ◽  
pp. 511-522 ◽  
Author(s):  
DS Goldman-Wohl ◽  
E Chan ◽  
D Baird ◽  
N Heintz
Keyword(s):  
Potassium Channel ◽  
Purkinje Cells ◽  
Cerebellar Nuclei ◽  
Deep Cerebellar Nuclei ◽  
Cerebellar Purkinje Cells

scholarly journals Calcium imaging reveals coordinated simple spike pauses in populations of Cerebellar Purkinje cells

2016 ◽  
Author(s):  
Jorge E. Ramirez ◽  
Brandon M. Stell
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Calcium Imaging ◽  
Spatial Organization ◽  
Cell Activity ◽  
Cerebellar Nuclei ◽  
Deep Cerebellar Nuclei ◽  
Firing Rates ◽  
Simple Spike ◽  
Cerebellar Purkinje Cells

The brain’s control of movement is thought to involve coordinated activity between cerebellar Purkinje cells. The results reported here demonstrate that somatic Ca2+ imaging is a faithful reporter of Na+-dependent “simple spike” pauses and enables us to optically record changes in firing rates in populations of Purkinje cells. This simultaneous calcium imaging of populations of Purkinje cells reveals a striking spatial organization of pauses in Purkinje cell activity between neighboring cells. The source of this organization is shown to be the presynaptic GABAergic network and blocking GABAARs abolishes the synchrony. These data suggest that presynaptic interneurons synchronize (in)activity between neighboring Purkinje cells and thereby maximize their effect on downstream targets in the deep cerebellar nuclei.

scholarly journals Cerebellar and vestibular nuclear synapses in the inferior olive have distinct release kinetics and neurotransmitters

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Josef Turecek ◽  
Wade G Regehr
Keyword(s):  
Purkinje Cells ◽  
Inferior Olive ◽  
Release Kinetics ◽  
Vestibular Nuclei ◽  
Cerebellar Nuclei ◽  
Climbing Fiber ◽  
Inhibitory Input ◽  
Deep Cerebellar Nuclei

The inferior olive (IO) is composed of electrically-coupled neurons that make climbing fiber synapses onto Purkinje cells. Neurons in different IO subnuclei are inhibited by synapses with wide ranging release kinetics. Inhibition can be exclusively synchronous, asynchronous, or a mixture of both. Whether the same boutons, neurons or sources provide these kinetically distinct types of inhibition was not known. We find that in mice the deep cerebellar nuclei (DCN) and vestibular nuclei (VN) are two major sources of inhibition to the IO that are specialized to provide inhibitory input with distinct kinetics. DCN to IO synapses lack fast synaptotagmin isoforms, release neurotransmitter asynchronously, and are exclusively GABAergic. VN to IO synapses contain fast synaptotagmin isoforms, release neurotransmitter synchronously, and are mediated by combined GABAergic and glycinergic transmission. These findings indicate that VN and DCN inhibitory inputs to the IO are suited to control different aspects of IO activity.

scholarly journals A Purkinje cell to parabrachial nucleus pathway enables broad cerebellar influence over the forebrain and emotional valence

2021 ◽  
Author(s):  
Christopher H. Chen ◽  
Leannah N. Newman ◽  
Amanda P. Stark ◽  
Katherine E. Bond ◽  
Dawei Zhang ◽  
...  
Keyword(s):  
Motor Control ◽  
Basal Forebrain ◽  
Emotional Regulation ◽  
Emotional Valence ◽  
Cerebellar Nuclei ◽  
Parabrachial Nucleus ◽  
Deep Cerebellar Nuclei ◽  
Cerebellar Dysfunction ◽  
Parabrachial Nuclei ◽  
Cerebellar Purkinje Cells

In addition to its well-known contributions to motor control and motor learning, the cerebellum is involved in language, emotional regulation, anxiety, and affect1-4. We found that suppressing the firing of cerebellar Purkinje cells (PCs) rapidly excites forebrain areas that could contribute to such functions, including the amygdala, basal forebrain, and septum, but that the classic cerebellar outputs, the deep cerebellar nuclei (DCN), do not project to these regions. Here we show that parabrachial nuclei (PBN) neurons that receive direct PC input, project to and influence all of these forebrain regions and many others. Furthermore, the function of this pathway is distinct from the canonical pathway: suppressing PC to PBN activity is aversive, whereas suppressing the PC to DCN pathway is rewarding. Therefore, the PBN pathway allows the cerebellum to influence the entire spectrum of valence, modulate the activity of forebrain regions known to regulate diverse nonmotor behaviors, and may be the substrate for many nonmotor disorders related to cerebellar dysfunction.

Structural and quantitative studies on the normal C3H and lurcher mutant mouse

1979 ◽  
Vol 287 (1020) ◽  
pp. 167-201 ◽  
Keyword(s):  
Purkinje Cells ◽  
Normal Mouse ◽  
Granule Cells ◽  
Cerebellar Nuclei ◽  
Inferior Olivary Nucleus ◽  
Deep Cerebellar Nuclei ◽  
Climbing Fibres ◽  
The Mean ◽  
Inferior Olivary ◽  
Olivary Nucleus

The cerebellum, the deep cerebellar nuclei, and the inferior olivary nucleus of the heterozygote Lurcher mutant mouse have been compared with the same structures in normal littermates. The comparison was made using light and electron microscopic methods for qualitative observations and light microscopic methods for quantitative observations. The study included the newborn period from 4 days of age up to 730 days, which is old age for a mouse. The cerebellum of the normal mouse is similar to that of many other species though apparently minor structural differences are seen. Amongst these was the similarity between the mouse climbing fibre and mossy fibre glomeruli which contrasts with the rat where they can be distinguished by the high density of synaptic vesicles and central cluster of mitochondria in the climbing fibres. In Golgi stained material the inferior olivary nucleus of the normal mouse showed cells with highly ramified dendrites and cells with simple dendrite patterns. In the adult Lurcher mouse the cerebellum is much smaller than is normal. There are no Purkinje cells and the internal granule cell layer is reduced in thickness and density. Examination of younger animals shows that Purkinje cells are present and that they undergo degeneration. In Golgi stained material from younger animals Purkinje cells often show more than one primary dendrite, sometimes as many as five, and somatic spines persist well beyond the first week of life. Cytoplasmic organelles often have a random orientation and the mitochondria are rounded rather like those seen in the nervous mutant. Granule cells in the adult Lurcher mutant are reduced in number and during the developmental period degenerative changes are seen. The Golgi cells and stellate cells are relatively normal and some cells, identified as basket cells, are seen. The inferior olivary nucleus is found with ease in the Lurcher mutant and is as extensive as in the normal mouse. However, in Golgi stained material only cells with highly ramified dendrites are seen. In addition the total number of neurons is reduced. It is possible that the neurons with a simple dendrite pattern have climbing fibres which pass only to the Purkinje cells. The deep cerebellar nuclei in the normal mouse cannot be separated easily into their three subdivisions, lateral, interpositus and medial. In the Lurcher mutant the neurons are of similar size to those of the normal mouse but they are crowded more closely together than is normal. In the Lurcher mutant as in the normal adult the neuronal cell bodies are covered with synapses and not with glial cells. Estimates of total cell numbers were made in order to obtain evidence about the time course of the development of the changes in structure and to make a detailed comparison between the normal mouse and the Lurcher mutant with respect to Purkinje cells, granule cells, olive neurons, and deep cerebellar nuclei neurons. In the normal mouse the mean number of Purkinje cells between 10 and 730 days was 177 000, s.d. ± 11600, n = 12. The number of granule cells probably reached a peak at about 17 days. At 26 days post-natal the number estimated was 27 million and at 730 days 28 million. The mean number of olive neurons between 14 and 730 days post-natal was 32700, s.d. ± 1900, 9; the mean number of deep cerebellar neurons counted at three adult ages was 17 600, s.d. ± 1800. In the adult the ratio of Purkinje cells to olive cells is ca . 5.4:1, of granule cells to Purkinje cells is ca. 170:1, of Purkinje cells to deep cerebellar nuclei neurons is 10:1, and of olive neurons to deep cerebellar nuclei neurons is 1.85:1. This last would chiefly be of interest if there are olive neurons projecting solely to deep cerebellar neurons. In the Lurcher mutant the number of Purkinje cells falls below normal from 8 days post-natally, reaches 10% of normal at 26 days and probably falls to zero at around 90 days. At this point such are the changes in the overall structure that confusion of Purkinje cells with Golgi cells may occur. At 4 days post-natal age the number of granule cells is smaller than normal by 25 % and this difference increases with age to a reduction of ca. 90 %. The number of olive cells is close to normal until 8 days of age, is only 60 % of normal at 15 days when the highest number is reached, and is 25 % of normal at 121 days. The deep cerebellar nuclei neuron numbers were the same as those in the normal. Included in the discussion is a detailed critical comparison of these results from the normal mouse with all previous estimates of cell numbers in the cerebellum. The lesion in Lurcher is compared with that found in the other mouse cerebellar mutants and with experimentally evoked lesions of the cerebellum. For the Lurcher mutant the tentative conclusion is that the primary lesion may arise in the Purkinje cells.

scholarly journals Disrupted Calcium Signaling in Animal Models of Human Spinocerebellar Ataxia (SCA)

2019 ◽  
Vol 21 (1) ◽  
pp. 216 ◽  
Author(s):  
Francesca Prestori ◽  
Francesco Moccia ◽  
Egidio D’Angelo
Keyword(s):  
Animal Models ◽  
Purkinje Cell ◽  
Calcium Signaling ◽  
Purkinje Cells ◽  
Motor Coordination ◽  
Cerebellar Atrophy ◽  
Cerebellar Nuclei ◽  
Spinocerebellar Ataxias ◽  
Cell Degeneration ◽  
Cerebellar Purkinje Cells

Spinocerebellar ataxias (SCAs) constitute a heterogeneous group of more than 40 autosomal-dominant genetic and neurodegenerative diseases characterized by loss of balance and motor coordination due to dysfunction of the cerebellum and its efferent connections. Despite a well-described clinical and pathological phenotype, the molecular and cellular events that underlie neurodegeneration are still poorly undaerstood. Emerging research suggests that mutations in SCA genes cause disruptions in multiple cellular pathways but the characteristic SCA pathogenesis does not begin until calcium signaling pathways are disrupted in cerebellar Purkinje cells. Ca2+ signaling in Purkinje cells is important for normal cellular function as these neurons express a variety of Ca2+ channels, Ca2+-dependent kinases and phosphatases, and Ca2+-binding proteins to tightly maintain Ca2+ homeostasis and regulate physiological Ca2+-dependent processes. Abnormal Ca2+ levels can activate toxic cascades leading to characteristic death of Purkinje cells, cerebellar atrophy, and ataxia that occur in many SCAs. The output of the cerebellar cortex is conveyed to the deep cerebellar nuclei (DCN) by Purkinje cells via inhibitory signals; thus, Purkinje cell dysfunction or degeneration would partially or completely impair the cerebellar output in SCAs. In the absence of the inhibitory signal emanating from Purkinje cells, DCN will become more excitable, thereby affecting the motor areas receiving DCN input and resulting in uncoordinated movements. An outstanding advantage in studying the pathogenesis of SCAs is represented by the availability of a large number of animal models which mimic the phenotype observed in humans. By mainly focusing on mouse models displaying mutations or deletions in genes which encode for Ca2+ signaling-related proteins, in this review we will discuss the several pathogenic mechanisms related to deranged Ca2+ homeostasis that leads to significant Purkinje cell degeneration and dysfunction.

Dynamic Synchronization of Purkinje Cell Simple Spikes

2006 ◽  
Vol 96 (6) ◽  
pp. 3485-3491 ◽  
Author(s):  
Soon-Lim Shin ◽  
Erik De Schutter
Keyword(s):  
Purkinje Cell ◽  
Firing Rate ◽  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Cerebellar Nuclei ◽  
Temporal Coding ◽  
Sharp Peak ◽  
Deep Cerebellar Nuclei

Purkinje cells (PCs) integrate all computations performed in the cerebellar cortex to inhibit neurons in the deep cerebellar nuclei (DCN). Simple spikes recorded in vivo from pairs of PCs separated by <100 μm are known to be synchronized with a sharp peak riding on a broad peak, but the significance of this finding is unclear. We show that the sharp peak consists exclusively of simple spikes associated with pauses in firing. The broader, less precise peak was caused by firing-rate co-modulation of faster firing spikes. About 13% of all pauses were synchronized, and these pauses had a median duration of 20 ms. As in vitro studies have reported that synchronous pauses can reliably trigger spikes in DCN neurons, we suggest that the subgroup of spikes causing the sharp peak is important for precise temporal coding in the cerebellum.

scholarly journals Climbing fiber synapses rapidly inhibit neighboring Purkinje cells via ephaptic coupling

2019 ◽  
Author(s):  
Kyung-Seok Han ◽  
Christopher H. Chen ◽  
Mehak M. Khan ◽  
Chong Guo ◽  
Wade G. Regehr
Keyword(s):  
Purkinje Cells ◽  
Inferior Olive ◽  
Cerebellar Nuclei ◽  
Extracellular Signals ◽  
Distance Dependence ◽  
Cerebellar Purkinje Cells ◽  
Motor Thalamus ◽  
Complex Spikes ◽  
Ephaptic Coupling

AbstractClimbing fibers (CFs) from the inferior olive (IO) provide strong excitatory inputs onto the dendrites of cerebellar Purkinje cells (PC), and trigger distinctive responses known as complex spikes (CSs). We find that in awake, behaving mice, a CS in one PC suppresses conventional simple spikes (SSs) in neighboring PCs for several milliseconds. This involves a novel form of ephaptic coupling, in which an excitatory synapse nonsynaptically inhibits neighboring cells by generating large negative extracellular signals near their dendrites. The distance dependence of CS-SS ephaptic signaling, combined with the known divergence of CF synapses made by IO neurons, allows a single IO neuron to influence the output of the cerebellum by synchronously suppressing the firing of potentially over one hundred PCs. Optogenetic studies in vivo and dynamic clamp studies in slice indicate that such brief PC suppression can effectively promote firing in neurons in the deep cerebellar nuclei and motor thalamus.

Evidence that the loss of Purkinje cells and deep cerebellar nuclei neurons in homozygous weaver is not related to neurogenetic patterns

2001 ◽  
Vol 19 (6) ◽  
pp. 599-610 ◽  
Author(s):  
Joaquı́n Martı́ ◽  
Katherine V Wills ◽  
Bernardino Ghetti ◽  
Shirley A Bayer
Keyword(s):  
Purkinje Cells ◽  
Cerebellar Nuclei ◽  
Deep Cerebellar Nuclei
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