Local Changes in the Excitability of the Cerebellar Cortex Produce Spatially Restricted Changes in Complex Spike Synchrony

Olivocerebellar activity is organized such that synchronous complex spikes occur primarily among Purkinje cells located within the same parasagittally oriented strip of cortex. Previous findings have shown that this synchrony distribution is modulated by the release of GABA and glutamate within the inferior olive, which probably act by controlling the efficacy of the electrotonic coupling between olivary neurons. The relative strengths of these two neurotransmitters in modulating the patterns of synchrony were compared by obtaining multiple electrode recordings of spontaneous crus 2a complex spike activity during intraolivary injection of solutions containing a GABAA (picrotoxin) and/or AMPA [1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium (NBQX)] receptor antagonist. Injection of either antagonist led to increased synchrony between cells located within the same parasagittally oriented ≈250-μm-wide cortical strip. Picrotoxin also increased complex spike synchrony among cells located in different cortical strips, leading to a less prominent banding pattern, whereas injections of NBQX tended to decrease complex spike synchrony among such cells, enhancing the banding pattern. The relative strength of these two classes of olivary afferents was assessed by first injecting one of the antagonists alone and then in combination with the other. The enhanced banding pattern of complex spike synchrony following injection of NBQX alone remained during the subsequent combined injection of both antagonists. Furthermore, the widespread synchronization of complex spike activity following injection of picrotoxin alone was partially or completely reversed by combined injection of picrotoxin and NBQX. Changes in the climbing fiber reflex induced by the intraolivary injections paralleled the changes observed for spontaneous complex spike activity, indicating that the effects of picrotoxin and NBQX on the synchrony distribution reflect changes in the pattern of effective coupling of inferior olivary neurons and demonstrating that synchronous complex spike activity does not require simultaneous excitatory input to olivary cells. Finally the pattern of synchrony during motor cortical stimulation was examined. It was found that the patterns of synchrony for motor-cortex-evoked complex spike activity were similar to those of spontaneous activity, indicating an important role for electrotonic coupling in determining the response of the olivocerebellar system to afferent input. Moreover, intraolivary injections of picrotoxin increased the spatial distribution of the evoked response. In sum, the results provide evidence for the hypothesis that electrotonic coupling of inferior olivary neurons via gap junctions is the mechanism underlying complex spike synchrony and that this coupling plays an important role in determining the responses of the olivocerebellar system to synaptic input.

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Responses of cerebellar Purkinje cells to slip of a hand-held object

Journal of Neurophysiology ◽

10.1152/jn.1992.67.3.483 ◽

1992 ◽

Vol 67 (3) ◽

pp. 483-495 ◽

Cited By ~ 89

Author(s):

C. Dugas ◽

A. M. Smith

Keyword(s):

Receptive Field ◽

Purkinje Cells ◽

Cerebellar Cortex ◽

Grip Force ◽

Receptive Fields ◽

Emg Activity ◽

Spike Discharge ◽

Complex Spike ◽

Simple Spike ◽

Force Pulse

1. Two monkeys were trained to grasp, lift, and hold a device between the thumb and forefinger for 1 s. The device was equipped with a position transducer and strain gauges that measured the horizontal grip force and the vertical lifting or load force. On selected blocks of 20-30 trials, a force-pulse perturbation was applied to the object during static holding to simulate object slip. The animals were required to resist this displacement by stiffening the joints of their wrists and fingers to obtain a fruit juice reward. Single cells in the hand representation area of the paravermal anterior lobe of the cerebellar cortex were recorded during perturbed and unperturbed holding. If conditions permitted, the cell discharge was also recorded during lifting of objects of various weights (15, 65, or 115 g) or different surface textures (sandpaper or polished metal), and when possible the cutaneous or proprioceptive fields of the neurons were characterized with the use of natural stimulation. 2. On perturbed trials, the force pulse was always applied to the manipulandum after it had been held stationary within the position window for 750 ms. The perturbation invariably elicited a reflexlike increase of electromyographic (EMG) activity in wrist and finger muscles, resulting in a time-locked increase in grip force that peaked at a latency between 50 and 100 ms. 3. The object-slip perturbation had a powerful effect on cerebellar cortical neurons at a mean latency of 45 +/- 14 (SD) ms. Reflexlike increases or decreases in simple spike discharge occurred in 55% (53/97) of unidentified cells and 49% (21/43) of Purkinje cells recorded in the anterior paravermal and lateral cerebellar cortex. 4. The perturbation failed to evoke complex spike responses from any of the Purkinje cells examined. All the perturbation-evoked activity changes involved modulation of the simple spike discharge. The perturbations stimulated the simple-spike receptive field of most Purkinje cells recorded here, which suggests that the short-latency unit responses were triggered by afferent stimulation. Only one Purkinje cell was found with a distinct complex-spike receptive field on the thumb, but this neuron did not respond to the perturbation. It appears that simple- and complex-spike to receptive fields are not always identical or even closely related. 5. The majority of Purkinje and unidentified neurons that responded to the perturbation had cutaneous receptive fields, although some had proprioceptive fields. Seventy-seven neurons were examined for peripheral receptive fields and were also tested with the perturbation.(ABSTRACT TRUNCATED AT 400 WORDS)

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Isochrony in the olivocerebellar system underlies complex spike synchrony

The Journal of Physiology ◽

10.1113/jphysiol.2006.571101 ◽

2006 ◽

Vol 573 (1) ◽

pp. 277-279 ◽

Cited By ~ 12

Author(s):

Eric J. Lang ◽

Rodolfo Llinás ◽

Izumi Sugihara

Keyword(s):

Spike Synchrony ◽

Complex Spike

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Excitatory afferent modulation of complex spike synchrony

The Cerebellum ◽

10.1080/14734220309420 ◽

2003 ◽

Vol 2 (3) ◽

pp. 165-170

Author(s):

Eric J Lang

Keyword(s):

Spike Synchrony ◽

Complex Spike

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Role of Myelination in the Development of a Uniform Olivocerebellar Conduction Time

Journal of Neurophysiology ◽

10.1152/jn.00922.2002 ◽

2003 ◽

Vol 89 (4) ◽

pp. 2259-2270 ◽

Cited By ~ 50

Author(s):

Eric J. Lang ◽

Jack Rosenbluth

Keyword(s):

Cerebellar Cortex ◽

Conduction Time ◽

Compensatory Mechanisms ◽

Response Latencies ◽

Complex Spike ◽

Normal Expression ◽

Myelin Deficient ◽

Inferior Olivary ◽

Complex Spikes

Purkinje cells generate simultaneous complex spikes as a result of olivocerebellar activity. This synchronization (to within 1 ms) is thought to result from electrotonic coupling of inferior olivary neurons. However, the distance from the inferior olive (IO) varies across the cerebellar cortex. Thus signals generated simultaneously at the IO should arrive asynchronously across the cerebellar cortex, unless the length differences are compensated for. Previously, it was shown that the conduction time from the IO to the cerebellar cortex remains nearly constant at ≈4 ms in the rat, implying the existence of such compensatory mechanisms. Here, we examined the role of myelination in generating a constant olivocerebellar conduction time by investigating the latency of complex spikes evoked by IO stimulation during development in normal rats and myelin-deficient mutants. In normal rats, myelination not only reduced overall olivocerebellar conduction time, but also disproportionately reduced the conduction time to vermal lobules, which had the longest response latencies prior to myelination. The net result was a nearly uniform conduction time. In contrast, in myelin-deficient rats, conduction time differences to different parts of the cerebellum remained during the same developmental period. Thus myelination is the primary factor in generating a uniform olivocerebellar conduction time. To test the importance of a uniform conduction time for generating synchronous complex spike activity, multiple electrode recordings were obtained from normal and myelin-deficient rats. Average synchrony levels were higher in normal rats than mutants. Thus the uniform conduction time achieved through myelination of olivocerebellar fibers appears to be essential for the normal expression of complex spike synchrony.

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Structure–Function Relationships between Aldolase C/Zebrin II Expression and Complex Spike Synchrony in the Cerebellum

Journal of Neuroscience ◽

10.1523/jneurosci.2170-14.2015 ◽

2015 ◽

Vol 35 (2) ◽

pp. 843-852 ◽

Cited By ~ 43

Author(s):

Shinichiro Tsutsumi ◽

Maya Yamazaki ◽

Taisuke Miyazaki ◽

Masahiko Watanabe ◽

Kenji Sakimura ◽

...

Keyword(s):

Structure Function ◽

Spike Synchrony ◽

Complex Spike ◽

Aldolase C ◽

Zebrin Ii

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Synchronous spiking of cerebellar Purkinje cells during control of movements

10.1101/2021.09.16.460700 ◽

2021 ◽

Author(s):

Ehsan Sedaghat-Nejad ◽

Jay S. Pi ◽

Paul Hage ◽

Mohammad Amin Fakharian ◽

Reza Shadmehr

Keyword(s):

Purkinje Cells ◽

Cerebellar Cortex ◽

Saccadic Eye Movements ◽

Spike Response ◽

Spike Synchrony ◽

Firing Rates ◽

Output Neurons ◽

Cerebellar Purkinje Cells ◽

P Cells ◽

Spike Firing

AbstractThe information that the brain transmits from one region to another is often viewed through the lens of firing rates. However, if the output neurons could vary the timing of their spikes with respect to each other, then through synchronization they could highlight information that may be critical for control of behavior. In the cerebellum, the computations that are performed by the cerebellar cortex are conveyed to the nuclei via inhibition. Yet, synchronous activity entrains nucleus neurons, making them fire. Does the cerebellar cortex rely on spike synchrony within populations of Purkinje cells (P-cells) to convey information to the nucleus? We recorded from multiple P-cells while marmosets performed saccadic eye movements and organized them into populations that shared a complex spike response to error. Before movement onset, P-cells transmitted information via a rate code: the simple spike firing rates predicted the direction and velocity of the impending saccade. However, during the saccade, the spikes became temporally aligned within the population, signaling when to stop the movement. Thus, the cerebellar cortex relies on spike synchronization within a population of P-cells, not individual firing rates, to convey to the nucleus when to stop a movement.

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