Changes in the Responses of Purkinje Cells in the Floccular Complex of Monkeys After Motor Learning in Smooth Pursuit Eye Movements

We followed simple- and complex-spike firing of Purkinje cells (PCs) in the floccular complex of the cerebellum through learned modifications of the pursuit eye movements of two monkeys. Learning was induced by double steps of target speed in which initially stationary targets move at a “learning” speed for 100 ms and then change to either a higher or lower speed in the same direction. In randomly interleaved control trials, targets moved at the learning speed in the opposite direction. When the learning direction was theon direction for simple-spike responses, learning was associated with statistically significant changes in simple-spike firing for 10 of 32 PCs. Of the 10 PCs that showed significant expressions of learning, 8 showed changes in simple-spike output in the expected direction: increased or decreased firing when eye acceleration increased or decreased through learning. There were no statistically significant changes in simple-spike responses or eye acceleration during pursuit in the control direction. When the learning direction was in the off direction for simple-spike responses, none of 15 PCs showed significant correlates of learning. Although changes in simple-spike firing were recorded in only a subset of PCs, analysis of the population response showed that the same relationship between population firing and eye acceleration obtained before and after learning. Thus learning is associated with changes that render the modified population response appropriate to drive the changed behavior. To analyze complex-spike firing during learning we correlated complex-spike firing in the second, third, and fourth 100 ms after the onset of target motion with the retinal image motion in the previous 100 ms. Data were largely consistent with previous evidence that image motion drives complex spikes with a direction selectivity opposite that for simple spikes. Comparison of complex-spike responses at different times after the onset of control and learning target motions in the learning direction implied that complex spikes could guide learning during decreases but not increases in eye acceleration. Learning caused increases or decreases in the sensitivity of complex spikes to image motion in parallel with changes in eye acceleration. Complex-spike responses were similar in all PCs, including many in which learning did not modify simple-spike responses. Our data do not disprove current theories of cerebellar learning but suggest that these theories would have to be modified to account for simple- and complex-spike firing of floccular Purkinje cells reported here.

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Visual responses of Purkinje cells in the cerebellar flocculus during smooth-pursuit eye movements in monkeys. II. Complex spikes

Journal of Neurophysiology ◽

10.1152/jn.1990.63.5.1262 ◽

1990 ◽

Vol 63 (5) ◽

pp. 1262-1275 ◽

Cited By ~ 125

Author(s):

L. S. Stone ◽

S. G. Lisberger

Keyword(s):

Eye Movements ◽

Firing Rate ◽

Target Motion ◽

Image Motion ◽

Retinal Slip ◽

Complex Spike ◽

Simple Spike ◽

P Cells ◽

Complex Spikes ◽

Spike Firing

1. We report the complex-spike responses of two groups of Purkinje cells (P-cells). The cell were classified according to their simple-spike firing during smooth eye movements evoked by visual and vestibular stimuli with the use of established criteria (Lisberger and Fuchs 1978; Stone and Lisberger 1990). During pursuit with the head fixed, ipsi gaze-velocity P-cells (GVP-cells) showed increased simple-spike firing when gaze moved toward the side of the recording, whereas down GVP-cells showed increased simple-spike firing when gaze moved downward. 2. During pursuit of sinusoidal target motion, the complex-spike firing rate was modulated out-of-phase with the simple-spike firing rate. Ipsi GVP-cells showed increased complex-spike firing during pursuit away from the side of the recording, and down GVP-cells showed increased complex-spike firing during upward pursuit. The strength of the complex-spike response increased as a function of the frequency of sinusoidal target motion. 3. GVP-cells showed directionally selective complex-spike responses during the initiation of pursuit to ramp target motion. Ipsi GVP-cells had increased complex-spike firing 100 ms after the onset of contralaterally directed target motion and decreased complex-spike activity after the onset of ipsilaterally directed target motion. Down GVP-cells had increased complex-spike firing 100 ms after the onset of upward target motion and decreased firing after the onset of downward target motion. As during sinusoidal target motion, each cell's simple- and complex-spike responses had the opposite directional preferences. 4. When the monkeys fixated a stationary target during a transient vestibular stimulus, the retinal slip caused by the 14-ms latency of the vestibuloocular reflex (VOR) affected the complex-spike firing rate. For ipsi GVP-cells, ipsilateral head motion caused transient contralateral image motion and an increase in complex-spike firing. The same vestibular stimulus in darkness caused an almost identical eye movement but had no effect on complex-spike firing. We conclude that complex spikes in ipsi GVP-cells are driven by contralaterally directed image motion. 5. To determine the events surrounding complex-spike firing during pursuit, we triggered averages of eye and target velocity on the occurrence of complex spikes during pursuit of sine-wave target motion. The averages revealed a transient pulse of retinal image motion that peaked approximately 100 ms before the complex spike. We conclude that complex spikes during steady-state pursuit are driven by the retinal slip associated with imperfect pursuit.(ABSTRACT TRUNCATED AT 400 WORDS)

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

10.1101/379149 ◽

2018 ◽

Cited By ~ 4

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.

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In vivo analysis of Purkinje cell firing properties during postnatal mouse development

Journal of Neurophysiology ◽

10.1152/jn.00586.2014 ◽

2015 ◽

Vol 113 (2) ◽

pp. 578-591 ◽

Cited By ~ 45

Author(s):

Marife Arancillo ◽

Joshua J. White ◽

Tao Lin ◽

Trace L. Stay ◽

Roy V. Sillitoe

Keyword(s):

Purkinje Cell ◽

Purkinje Cells ◽

Motor Behavior ◽

Developmental Trajectories ◽

Cell Activity ◽

Mouse Development ◽

Complex Spike ◽

Simple Spike ◽

Spike Firing

Purkinje cell activity is essential for controlling motor behavior. During motor behavior Purkinje cells fire two types of action potentials: simple spikes that are generated intrinsically and complex spikes that are induced by climbing fiber inputs. Although the functions of these spikes are becoming clear, how they are established is still poorly understood. Here, we used in vivo electrophysiology approaches conducted in anesthetized and awake mice to record Purkinje cell activity starting from the second postnatal week of development through to adulthood. We found that the rate of complex spike firing increases sharply at 3 wk of age whereas the rate of simple spike firing gradually increases until 4 wk of age. We also found that compared with adult, the pattern of simple spike firing during development is more irregular as the cells tend to fire in bursts that are interrupted by long pauses. The regularity in simple spike firing only reached maturity at 4 wk of age. In contrast, the adult complex spike pattern was already evident by the second week of life, remaining consistent across all ages. Analyses of Purkinje cells in alert behaving mice suggested that the adult patterns are attained more than a week after the completion of key morphogenetic processes such as migration, lamination, and foliation. Purkinje cell activity is therefore dynamically sculpted throughout postnatal development, traversing several critical events that are required for circuit formation. Overall, we show that simple spike and complex spike firing develop with unique developmental trajectories.

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Simple spike responses of gaze velocity Purkinje cells in the floccular lobe of the monkey during the onset and offset of pursuit eye movements

Journal of Neurophysiology ◽

10.1152/jn.1994.72.4.2045 ◽

1994 ◽

Vol 72 (4) ◽

pp. 2045-2050 ◽

Cited By ~ 39

Author(s):

R. J. Krauzlis ◽

S. G. Lisberger

Keyword(s):

Eye Movements ◽

Firing Rate ◽

Purkinje Cells ◽

Target Motion ◽

Transient Increase ◽

Pursuit Eye Movements ◽

Simple Spike ◽

Preferred Direction ◽

Population Average ◽

Ventral Paraflocculus

1. We recorded the simple spike firing rate of gaze velocity Purkinje cells (GVP-cells) in the flocculus/ventral paraflocculus of two monkeys during the smooth pursuit eye movements evoked by a target that was initially at rest, started suddenly, moved at a constant velocity, and then stopped. 2. For target motion in the preferred direction, GVP-cells showed a large transient increase in firing rate at the onset of pursuit, a smaller but sustained increase during the maintenance of pursuit, and a smooth return to baseline firing with little undershoot at the offset of pursuit. For target motion in the nonpreferred direction, GVP-cells showed a small decrease in firing rate at the onset of pursuit, a similar sustained decrease during the maintenance of pursuit, but a large transient increase in firing rate at the offset of pursuit before returning to baseline firing. 3. We pooled the data in our sample of horizontal GVP-cells by subtracting the population average of firing rate recorded during pursuit in the nonpreferred direction from the population average recorded during pursuit in the preferred direction. We transformed this net population average by passing it through a model of the brain stem final common pathway and the oculomotor plant. This yielded a signal that closely matched the observed trajectory of eye velocity during pursuit. We conclude that the transient overshoots exhibited in the firing rate of GVP-cells can provide appropriate compensation for the lagging dynamics of the oculomotor plant.

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Increase in Purkinje cell gain associated with naturally activated climbing fiber input

Journal of Neurophysiology ◽

10.1152/jn.1983.50.1.205 ◽

1983 ◽

Vol 50 (1) ◽

pp. 205-219 ◽

Cited By ~ 88

Author(s):

T. J. Ebner ◽

Q. X. Yu ◽

J. R. Bloedel

Keyword(s):

Purkinje Cell ◽

Purkinje Cells ◽

Mossy Fiber ◽

Climbing Fiber ◽

Peripheral Stimulus ◽

Short Term ◽

Spike Response ◽

Complex Spike ◽

Simple Spike ◽

Complex Spikes

These experiments were designed to test the hypothesis that climbing fiber inputs evoked by a peripheral stimulus increase the responsiveness of Purkinje cells to mossy fiber inputs. This hypothesis was based on a previous series of observations demonstrating that spontaneous climbing fiber inputs are associated with an accentuation of the Purkinje cell responses to subsequent mossy fiber inputs (10, 12). Furthermore, short-term nonpersistent interactions between climbing and mossy fiber inputs have been an important aspect of many theories of cerebellar function (5, 7, 8, 12, 36). Extracellular unitary recordings were made from Purkinje cells in lobule V of decerebrate, unanesthetized cats. To activate mossy and climbing fiber inputs, the forepaw was passively flexed by a Ling vibrator system. A data analysis was developed to sort the simple spike trials into two groups, based on the presence or absence of complex spikes activated by the stimulus. In addition, during those trials in which complex spikes were activated, the simple spike train was aligned on the occurrence of the complex spike. For each simple spike response to the forepaw input, the average firing rate during the response was compared to background both in those trials in which complex spikes were activated and in those in which they were not. The ratio of the response amplitudes in the histograms constructed from these two groups of trials permitted a quantification of the change in responsiveness when climbing fiber inputs were activated. The results show that both excitatory and inhibitory simple spike responses are accentuated when associated with the activation of a complex spike. Using an arbitrary level of a gain change ratio of 120% as indicating a significant modification, 64% of the response components analyzed increased their amplitude when climbing fiber input was present. Simple spike response components occurring prior to complex spike activation were usually not accentuated, although in a few cells the amplitude of this component of the response increased. In addition, in a small number of cells the occurrence of complex spikes was associated with a new simple spike component. For excitatory responses, the magnitude of the gain change ratio was shown to be inversely related to the amplitude of the simple spike response evoked by the mossy fiber inputs. The data obtained is consistent with the hypothesis that the climbing fiber input is associated with an increase in the responsiveness of Purkinje cells to mossy fiber inputs. The increased responsiveness occurs whether the simple spike modulation evoked by the peripheral stimulus is excitatory or inhibitory. The change in responsiveness is short term and nonpersistent. It is argued that the activation of climbing fiber inputs to the cerebellar cortex is associated with an increase in the gain of Purkinje cells to mossy fiber inputs activated by natural peripheral stimuli.

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An active membrane model of the cerebellar Purkinje cell II. Simulation of synaptic responses

Journal of Neurophysiology ◽

10.1152/jn.1994.71.1.401 ◽

1994 ◽

Vol 71 (1) ◽

pp. 401-419 ◽

Cited By ~ 163

Author(s):

E. De Schutter ◽

J. M. Bower

Keyword(s):

Purkinje Cell ◽

Purkinje Cells ◽

Average Frequency ◽

Climbing Fiber ◽

Cerebellar Purkinje Cell ◽

Inhibitory Synapses ◽

Complex Spike ◽

Simple Spike ◽

Spike Firing

1. Both excitatory and inhibitory postsynaptic channels were added to a previously described complex compartmental model of a cerebellar Purkinje cell to examine model responses to synaptic inputs. All model parameters remained as described previously, leaving maximum synaptic conductance as the only parameter that was tuned in the studies described in this paper. Under these conditions the model was capable of reproducing physiological recorded responses to each of the major types of synaptic input. 2. When excitatory synapses were activated on the smooth dendrites of the model, the model generated a complex dendritic Ca2+ spike similar to that generated by climbing fiber inputs. Examination of the model showed that activation of P-type Ca2+ channels in both the smooth and spiny dendrites augmented the depolarization during the complex spike and that Ca(2+)-activated K+ channels in the same dendritic regions determined the duration of the spike. When these synapses were activated under simulated current-clamp conditions the model also generated the characteristic dual reversal potential of the complex spike. The shape of the dendritic complex spike could be altered by changing the maximum conductance of the climbing fiber synapse and thus the amount of Ca2+ entering the cell. 3. To explore the background simple spike firing properties of Purkinje cells in vivo we added excitatory “parallel fiber” synapses to the spiny dendritic branches of the model. Continuous asynchronous activation of these granule cell synapses resulted in the generation of spontaneous sodium spikes. However, very low asynchronous input frequencies produced a highly regular, very fast rhythm (80–120 Hz), whereas slightly higher input frequencies resulted in Purkinje cell bursting. Both types of activity are uncharacteristic of in vivo Purkinje cell recordings. 4. Inhibitory synapses of the sort presumably generated by stellate cells were also added to the dendritic tree. When asynchronous activation of these inhibitory synapses was combined with continuous asynchronous excitatory input the model generated somatic action potentials in a much more stochastic pattern typical of real Purkinje cells. Under these conditions simulated inter-spike interval distributions resembled those found in experimental recordings. Also, as with in vivo recordings, the model did not generate dendritic bursts. This was mainly due to inhibition that suppressed the generation of dendritic Ca2+ spikes. 5. In the presence of asynchronous inhibition, changes in the average frequency of excitatory inputs modulated background simple spike firing frequencies in the natural range of Purkinje cell firing frequencies (30–100 Hz). This modulation was very sensitive to small changes in the average frequency of excitatory inputs.(ABSTRACT TRUNCATED AT 400 WORDS)

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Effect of simple spike firing mode on complex spike firing rate and waveform in cerebellar Purkinje cells in non-anesthetized mice

Neuroscience Letters ◽

10.1016/j.neulet.2004.05.109 ◽

2004 ◽

Vol 367 (2) ◽

pp. 171-176 ◽

Cited By ~ 15

Author(s):

Laurent Servais ◽

Bertrand Bearzatto ◽

Raphaël Hourez ◽

Bernard Dan ◽

Serge N. Schiffmann ◽

...

Keyword(s):

Firing Rate ◽

Purkinje Cells ◽

Complex Spike ◽

Simple Spike ◽

Firing Mode ◽

Cerebellar Purkinje Cells ◽

Spike Firing

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Molecular layer interneurons shape the spike activity of cerebellar Purkinje cells

10.1101/376517 ◽

2018 ◽

Author(s):

Amanda M. Brown ◽

Marife Arancillo ◽

Tao Lin ◽

Daniel R. Catt ◽

Joy Zhou ◽

...

Keyword(s):

Purkinje Cell ◽

Purkinje Cells ◽

Stellate Cell ◽

Molecular Layer ◽

Complex Spike ◽

Gabaergic Neurotransmission ◽

Simple Spike ◽

Firing Properties ◽

Spike Firing

One-sentence summaryCerebellar stellate cells and basket cells shape distinct Purkinje cell firing propertiesAbstractPurkinje cells receive synaptic input from several classes of interneurons. Here, we address the roles of inhibitory molecular layer interneurons in establishing Purkinje cell function in vivo. Using conditional genetics approaches in mice, we compare how the lack of stellate cell versus basket cell GABAergic neurotransmission sculpts the firing properties of Purkinje cells. We take advantage of an inducible Ascl1CreER allele to spatially and temporally target the deletion of the vesicular GABA transporter, Vgat, in developing neurons. Selective depletion of basket cell GABAergic neurotransmission increases the frequency of Purkinje cell simple spike firing and decreases the frequency of complex spike firing in adult behaving mice. In contrast, lack of stellate cell communication increases the regularity of Purkinje cell simple spike firing while increasing the frequency of complex spike firing. Our data uncover complementary roles for molecular layer interneurons in shaping the rate and pattern of Purkinje cell activity in vivo.

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