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 Synaptic inputs to the inferior olive from cerebellar and vestibular nuclei have distinct release kinetics and neurotransmitters

2020 ◽  
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 ◽  
Synaptic Inputs

AbstractThe inferior olive (IO) is comprised 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 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.

The anlage of the cerebellar nuclei in chick after early extirpation of the vestibular region

Development ◽  
1964 ◽  
Vol 12 (1) ◽  
pp. 51-64
Author(s):  
Sven-Ingvar Rüdeberg
Keyword(s):  
Cell Layer ◽  
Relevant Literature ◽  
Vestibular Nuclei ◽  
Cerebellar Nuclei ◽  
Embryonic Brain ◽  
Stratum Granulosum ◽  
Deep Cerebellar Nuclei ◽  
The Matrix ◽  
Matrix Region ◽  
A Cell

Diverse opinions have been advanced in the relevant literature concerning the embryological origin of the cells constituting the deep cerebellar nuclei in vertebrates. A number of different regions in the embryonic brain have in turn been regarded as the matrix region of the cerebellar nuclei; these are given below. 1. The vestibular nuclei. Dowd (1929, pig), Larsell (1935, opossum), Nistri, Fabiani & Cannizzaro (1959, man). 2. The cerebellar neural epithelium. Gentès (1906, chick), Hajashi (1924, man), Tello (1940, mouse), Baffoni (1956, cat), Baffoni & D'Ancona (1958, chick and pigeon), Baffoni (1959, toad). 3. The cerebellar neural epithelium, probably reinforced with cells from the superficial stratum granulosum, in species possessing such a cell-layer. Rüdeberg (1961, lamprey, dog-fish, pike, frog, chick, pigeon, cow and man). 4. The inner cell layer of the embryonic cerebellar cortex. Loewe (1880, rabbit [nucleus lateralis cerebelli]). Nistri & Fabiani (1956, man) traced the anlagen of the cerebellar nuclei from the neural epithelium of the cerebellum.

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.

Dynamical Working Memory and Timed Responses: The Role of Reverberating Loops in the Olivo-Cerebellar System

2002 ◽  
Vol 14 (11) ◽  
pp. 2597-2626 ◽  
Author(s):  
Werner M. Kistler ◽  
Chris I. De Zeeuw
Keyword(s):  
Working Memory ◽  
Discrete Model ◽  
Inferior Olive ◽  
Mean Field ◽  
Cerebellar Nuclei ◽  
Field Approximation ◽  
Network Effect ◽  
Mean Field Approximation ◽  
Inhibitory Input ◽  
Cerebellar Purkinje Cells

This article explores dynamical properties of the olivo-cerebellar system that arise from the specific wiring of inferior olive (IO), cerebellar cortex, and deep cerebellar nuclei (DCN). We show that the irregularity observed in the firing pattern of the IO neurons is not necessarily produced by noise but can instead be the result of a purely deterministic network effect. We propose that this effect can serve as a dynamical working memory or as a neuronal clock with a characteristic timescale of about 100 ms that is determined by the slow calcium dynamics of IO and DCN neurons. This concept provides a novel explanation of how the cerebellum can solve timing tasks on a timescale that is two orders of magnitude longer than the millisecond timescale usually attributed to neuronal dynamics. One of the key ingredients of our model is the observation that due to postinhibitory rebound, DCN neurons can be driven by GABAergic (“inhibitory”) input from cerebellar Purkinje cells. Topographic projections from the DCN to the IO form a closed reverberating loop with an overall synaptic transmission delay of about 100 ms that is in resonance with the intrinsic oscillatory properties of the inferior olive. We use a simple time-discrete model based on McCulloch-Pitts neurons in order to investigate in a first step some of the fundamental properties of a network with delayed reverberating projections. The macroscopic behavior is analyzed by means of a mean-field approximation. Numerical simulations, however, show that the microscopic dynamics has a surprisingly rich structure that does not show up in a mean-field description. We have thus performed extensive numerical experiments in order to quantify the ability of the network to serve as a dynamical working memory and its vulnerability by noise. In a second step, we develop a more realistic conductance-based network model of the inferior olive consisting of about 20 multicompartment neurons that are coupled by gap junctions and receive excitatory and inhibitory synaptic input via AMPA and GABAergic synapses. The simulations show that results for the time-discrete model hold true in a time-continuous description.

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.

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