scholarly journals Distributed sensory coding by cerebellar complex spikes in units of cortical segments

2020 ◽  
Author(s):  
Takayuki Michikawa ◽  
Takamasa Yoshida ◽  
Satoshi Kuroki ◽  
Takahiro Ishikawa ◽  
Shinji Kakei ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Sensory Processing ◽  
Inferior Olive ◽  
Dorsal Surface ◽  
Population Coding ◽  
Sensory Coding ◽  
Trial Basis ◽  
Complex Spikes ◽  
Stimulation Of

SummarySensory processing is essential for motor control. Climbing fibers from the inferior olive transmit sensory signals to Purkinje cells, but how the signals are represented in the cerebellar cortex remains elusive. We examined the olivocerebellar organization of the mouse brain by optically measuring complex spikes (CSs) evoked by climbing fiber inputs over the entire dorsal surface of the cerebellum. We discovered that the surface was divided into approximately 200 segments each composed of ∼100 Purkinje cells that fired CSs synchronously. Our in vivo imaging of evoked responses revealed that whereas stimulation of four limb muscles individually similar global CS responses across nearly all segments, the timing and location of a stimulus were derived by Bayesian inference from coordinated activation and inactivation of multiple segments on a single trial basis. Our findings suggest that the cerebellum performs segment-based distributed population coding by assembling probabilistic sensory representation in individual segments.

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.

scholarly journals Cerebellar implementation of movement sequences through feedback

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Andrei Khilkevich ◽  
Juan Zambrano ◽  
Molly-Marie Richards ◽  
Michael Dean Mauk
Keyword(s):  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
General Framework ◽  
Eyelid Conditioning ◽  
Mossy Fibers ◽  
Learning Processes ◽  
Single Component ◽  
Associate Learning ◽  
Stimulation Of

Most movements are not unitary, but are comprised of sequences. Although patients with cerebellar pathology display severe deficits in the execution and learning of sequences (Doyon et al., 1997; Shin and Ivry, 2003), most of our understanding of cerebellar mechanisms has come from analyses of single component movements. Eyelid conditioning is a cerebellar-mediated behavior that provides the ability to control and restrict inputs to the cerebellum through stimulation of mossy fibers. We utilized this advantage to test directly how the cerebellum can learn a sequence of inter-connected movement components in rabbits. We show that the feedback signals from one component are sufficient to serve as a cue for the next component in the sequence. In vivo recordings from Purkinje cells demonstrated that all components of the sequence were encoded similarly by cerebellar cortex. These results provide a simple yet general framework for how the cerebellum can use simple associate learning processes to chain together a sequence of appropriately timed responses.

scholarly journals Distinct responses of Purkinje neurons and roles of simple spikes during associative motor learning in larval zebrafish

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Thomas C Harmon ◽  
Uri Magaram ◽  
David L McLean ◽  
Indira M Raman
Keyword(s):  
Motor Learning ◽  
Purkinje Cells ◽  
Tactile Stimulation ◽  
Visual Stimulation ◽  
Purkinje Neurons ◽  
Related Activity ◽  
Larval Zebrafish ◽  
Whole Cell Recordings ◽  
Complex Spikes ◽  
Stimulation Of

To study cerebellar activity during learning, we made whole-cell recordings from larval zebrafish Purkinje cells while monitoring fictive swimming during associative conditioning. Fish learned to swim in response to visual stimulation preceding tactile stimulation of the tail. Learning was abolished by cerebellar ablation. All Purkinje cells showed task-related activity. Based on how many complex spikes emerged during learned swimming, they were classified as multiple, single, or zero complex spike (MCS, SCS, ZCS) cells. With learning, MCS and ZCS cells developed increased climbing fiber (MCS) or parallel fiber (ZCS) input during visual stimulation; SCS cells fired complex spikes associated with learned swimming episodes. The categories correlated with location. Optogenetically suppressing simple spikes only during visual stimulation demonstrated that simple spikes are required for acquisition and early stages of expression of learned responses, but not their maintenance, consistent with a transient, instructive role for simple spikes during cerebellar learning in larval zebrafish.

TRPV1 receptor blockade is ineffective in different in vivo models of migraine

Cephalalgia ◽  
2010 ◽  
Vol 31 (2) ◽  
pp. 172-180 ◽  
Author(s):  
Oliver Summ ◽  
Philip R Holland ◽  
Simon Akerman ◽  
Peter J Goadsby
Keyword(s):  
Electrical Stimulation ◽  
Sensory Processing ◽  
Dynamic Range ◽  
Sprague Dawley ◽  
In Vivo Models ◽  
Trpv1 Receptor ◽  
C Fibers ◽  
Trpv1 Receptors ◽  
Stimulation Of

Background: It has been proposed that TRPV1 receptors may play a role modulating trigeminal sensory processing. We used models of trigeminovascular nociceptive activation to study the involvement of TRPV1 receptors in the rat. Due to a possible role of TRPV1 receptors in cortical spreading depression (CSD), an experimental phenomenon sharing many features with migraine aura, we also utilized a model of mechanically induced CSD. Methods: Male Sprague Dawley rats ( N = 39) were anesthetized and cannulated for monitoring and drug administration to study the effects of the TRPV1 receptor antagonist A-993610 (8 mg kg−1 IV). Wide-dynamic-range neurons, responding to electrical stimulation of the middle meningeal artery (MMA)/dura mater were identified and recorded using electrophysiological techniques. Intravital microscopy was used to study neurogenic dural vasodilation (NDV) of the MMA comparing capsaicin and electrical stimulation, and the effect of A-993610 on mechanically induced CSD was examined. Results: Administration of A-993610 had no significant effect on trigeminal firing of A- or C-fibers elicited by electrical stimulation of the MMA. It also showed no effect on NDV whilst blocking vasodilation due to intravenous capsaicin injection. The mechanically induced CSD response could not be altered by A-993610 administration. Conclusions: Although there is evidence that TRPV1 receptors play an important role in sensory processing in general, the new data do not support a role in the treatment of acute migraine.

scholarly journals Neurons of the inferior olive respond to broad classes of sensory input while subject to homeostatic control

2018 ◽  
Author(s):  
Chiheng Ju ◽  
Laurens W.J. Bosman ◽  
Tycho M. Hoogland ◽  
Arthiha Velauthapillai ◽  
Pavithra Murugesan ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Inferior Olive ◽  
Recent History ◽  
Climbing Fibre ◽  
Homeostatic Control ◽  
Complex Spike ◽  
History Of ◽  
Sensory Evoked ◽  
Complex Spikes ◽  
Spike Firing

AbstractCerebellar Purkinje cells integrate sensory information with motor efference copies to adapt movements to behavioural and environmental requirements. They produce complex spikes that are triggered by the activity of climbing fibres originating in neurons of the inferior olive. These complex spikes can shape the onset, amplitude and direction of movements as well as the adaptation of such movements to sensory feedback. Clusters of nearby inferior olive neurons project to parasagittally aligned stripes of Purkinje cells, referred to as “microzones”. It is currently unclear to what extent individual Purkinje cells within a single microzone integrate climbing fibre inputs from multiple sources of different sensory origins, and to what extent sensory-evoked climbing fibre responses depend on the strength and recent history of activation. Here we imaged complex spike responses in cerebellar lobule crus 1 to various types of sensory stimulation in awake mice. We find that different sensory modalities and receptive fields have a mild, but consistent, tendency to converge on individual Purkinje cells. Purkinje cells encoding the same stimulus show increased events with coherent complex spike firing and tend to lie close together. Moreover, whereas complex spike firing is only mildly affected by variations in stimulus strength, it strongly depends on the recent history of climbing fibre activity. Our data point towards a mechanism in the olivo-cerebellar system that regulates complex spike firing during mono- or multisensory stimulation around a relatively low set-point, highlighting an integrative coding scheme of complex spike firing under homeostatic control.

scholarly journals Multiple signals evoked by unisensory stimulation converge onto cerebellar granule and Purkinje cells in mice

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Misa Shimuta ◽  
Izumi Sugihara ◽  
Taro Ishikawa
Keyword(s):  
Purkinje Cells ◽  
Granule Cells ◽  
Late Phase ◽  
Two Phase ◽  
Cell Responses ◽  
Different Types ◽  
Peripheral Sensory ◽  
Whole Cell Recordings ◽  
Complex Spikes

AbstractThe cerebellum receives signals directly from peripheral sensory systems and indirectly from the neocortex. Even a single tactile stimulus can activate both of these pathways. Here we report how these different types of signals are integrated in the cerebellar cortex. We used in vivo whole-cell recordings from granule cells and unit recordings from Purkinje cells in mice in which primary somatosensory cortex (S1) could be optogenetically inhibited. Tactile stimulation of the upper lip produced two-phase granule cell responses (with latencies of ~8 ms and 29 ms), for which only the late phase was S1 dependent. In Purkinje cells, complex spikes and the late phase of simple spikes were S1 dependent. These results indicate that individual granule cells combine convergent inputs from the periphery and neocortex and send their outputs to Purkinje cells, which then integrate those signals with climbing fiber signals from the neocortex.

scholarly journals Direct translation of climbing fiber burst-mediated sensory coding into post-synaptic Purkinje cell dendritic calcium

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Seung-Eon Roh ◽  
Seung Ha Kim ◽  
Changhyeon Ryu ◽  
Chang-Eop Kim ◽  
Yong Gyu Kim ◽  
...  
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Sensory Information ◽  
Sensory Coding ◽  
Information Coding ◽  
Direct Translation ◽  
Spike Number ◽  
Cerebellar Purkinje Cells ◽  
Complex Spikes

Climbing fibers (CFs) generate complex spikes (CS) and Ca2+ transients in cerebellar Purkinje cells (PCs), serving as instructive signals. The so-called 'all-or-none' character of CSs has been questioned since the CF burst was described. Although recent studies have indicated a sensory-driven enhancement of PC Ca2+ signals, how CF responds to sensory events and contributes to PC dendritic Ca2+ and CS remains unexplored. Here, single or simultaneous Ca2+ imaging of CFs and PCs in awake mice revealed the presynaptic CF Ca2+ amplitude encoded the sensory input’s strength and directly influenced post-synaptic PC dendritic Ca2+ amplitude. The sensory-driven variability in CF Ca2+ amplitude depended on the number of spikes in the CF burst. Finally, the spike number of the CF burst determined the PC Ca2+ influx and CS properties. These results reveal the direct translation of sensory information-coding CF inputs into PC Ca2+, suggesting the sophisticated role of CFs as error signals.

scholarly journals Convergence of unisensory-evoked signals via multiple pathways to the cerebellum

2019 ◽  
Author(s):  
Misa Shimuta ◽  
Izumi Sugihara ◽  
Taro Ishikawa
Keyword(s):  
Purkinje Cells ◽  
Granule Cells ◽  
Late Phase ◽  
Two Phase ◽  
Cell Responses ◽  
Different Types ◽  
Peripheral Sensory ◽  
Whole Cell Recordings ◽  
Complex Spikes

SUMMARYThe cerebellum receives signals directly from peripheral sensory systems and indirectly from the neocortex. To reveal how these different types of signals are processed in the cerebellar cortex, in vivo whole-cell recordings from granule cells and unit recordings from Purkinje cells were performed in mice in which primary somatosensory cortex (S1) could be optogenetically inhibited. Tactile stimulation of the upper lip produced two-phase granule cell responses (with latencies of ∼ 8 ms and 28 ms), for which only the late phase was S1 dependent. Complex spikes and the late phase of simple spikes in Purkinje cells were also S1 dependent. These results indicate that individual granule cells integrate convergent inputs from the periphery and neocortex, and send their outputs to Purkinje cells, which then combine those signals with climbing fiber signals from the neocortex.

Floccular Modulation of Vestibuloocular Pathways and Cerebellum-Related Plasticity: An In Vitro Whole Brain Study

2000 ◽  
Vol 84 (5) ◽  
pp. 2514-2528 ◽  
Author(s):  
Alexander L. Babalian ◽  
Pierre-Paul Vidal
Keyword(s):  
Purkinje Cells ◽  
Nerve Stimulation ◽  
Inferior Olive ◽  
Vestibular Nuclei ◽  
Vestibular Nerve ◽  
Abducens Nucleus ◽  
Postsynaptic Potentials ◽  
Oculomotor Nerves ◽  
Stimulation Of

The isolated whole brain (IWB) preparation of the guinea pig was used to investigate the floccular modulation of vestibular-evoked responses in abducens and oculomotor nerves and abducens nucleus; for identification of flocculus target neurons (FTNs) in the vestibular nuclei and intracellular study of some of their physiological properties; to search for possible flocculus-dependent plasticity at the FTN level by pairing of vestibular nerve and floccular stimulations; and to study the possibility of induction of long-term depression (LTD) in Purkinje cells by paired stimulation of the inferior olive and vestibular nerve. Stimulation of the flocculus had only effects on responses evoked from the ipsilateral (with respect to the stimulated flocculus) vestibular nerve. Floccular stimulation significantly inhibited the vestibular-evoked discharges in oculomotor nerves on both sides and the inhibitory field potential in the ipsilateral abducens nucleus while the excitatory responses in the contralateral abducens nerve and nucleus were free from such inhibition. Eleven second-order vestibular neurons were found to receive a short-latency monosynaptic inhibitory input from the flocculus and were thus characterized as FTNs. Monosynaptic inhibitory postsynaptic potentials from the flocculus were bicuculline sensitive, suggesting a GABAA-ergic transmission from Purkinje cells to FTNs. Two of recorded FTNs could be identified as vestibulospinal neurons by their antidromic activation from the cervical segments of the spinal cord. Several pairing paradigms were investigated in which stimulation of the flocculus could precede, coincide with, or follow the vestibular nerve stimulation. None of them led to long-term modification of responses in the abducens nucleus or oculomotor nerve evoked by activation of vestibular afferents. On the other hand, pairing of the inferior olive and vestibular nerve stimulation resulted in approximately a 30% reduction of excitatory postsynaptic potentials evoked in Purkinje cells by the vestibular nerve stimulation. This reduction was pairing-specific and lasted throughout the entire recording time of the neurons. Thus in the IWB preparation, we were able to induce a LTD in Purkinje cells, but we failed to detect traces of flocculus-dependent plasticity at the level of FTNs in vestibular nuclei. Although these data cannot rule out the possibility of synaptic modifications in FTNs and/or at other brain stem sites under different experimental conditions, they are in favor of the hypothesis that the LTD in the flocculus could be the essential mechanism of cellular plasticity in the vestibuloocular pathways.

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