Complex spike firing adapts to saliency of inputs and engages readiness to act

AbstractThe cerebellum is involved in cognition next to motor coordination. During complex tasks, climbing fiber input to the cerebellum can deliver seemingly opposite signals, covering both motor and non-motor functions. To elucidate this ambiguity, we hypothesized that climbing fiber activity represents the saliency of inputs leading to action-readiness. We addressed this hypothesis by recording Purkinje cell activity in lateral cerebellum of awake mice learning go/no-go decisions based on entrained saliency of different sensory stimuli. As training progressed, the timing of climbing fiber signals switched in a coordinated fashion with that of Purkinje cell simple spikes towards the moment of occurrence of the salient stimulus that required action. Trial-by-trial analysis indicated that emerging climbing fiber activity is not linked to individual motor responses or rewards per se, but rather reflects the saliency of a particular sensory stimulus that engages a general readiness to act, bridging the non-motor with the motor functions.In briefMice were trained to identify the saliency of different sensory inputs in that they had to learn to ignore a prominent sound cue and respond to a light tactile cue in a Go/No-Go licking task. As the mice learned to discriminate the two inputs and respond to the proper signal, the Purkinje cells in the lateral cerebellum switched their climbing fiber activity (i.e., complex spike activity) towards the moment of occurrence of the salient stimulus that required a response, while concomitantly shifting the phase of their simple spike modulation. Trial-by-trial analysis indicates that the emerging climbing fiber activity is not linked to the occurrence of the motor response or reward per se, but rather reflects the saliency of a particular sensory stimulus engaging a general readiness to act.

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Climbing Fiber Discharge Regulates Cerebellar Functions by Controlling the Intrinsic Characteristics of Purkinje Cell Output

Journal of Neurophysiology ◽

10.1152/jn.00627.2006 ◽

2007 ◽

Vol 97 (4) ◽

pp. 2590-2604 ◽

Cited By ~ 43

Author(s):

Bruce E. McKay ◽

Jordan D. T. Engbers ◽

W. Hamish Mehaffey ◽

Grant R. J. Gordon ◽

Michael L. Molineux ◽

...

Keyword(s):

Purkinje Cell ◽

Purkinje Cells ◽

Motor Coordination ◽

Climbing Fiber ◽

State Transitions ◽

Cellular Functions ◽

Complex Spike ◽

Network Activation ◽

Cellular Factors

The contribution of Purkinje cells to cerebellar motor coordination and learning is determined in part by the chronic and acute effects of climbing fiber (CF) afferents. Whereas the chronic effects of CF discharge, such as the depression of conjunctive parallel fiber (PF) inputs, are well established, the acute cellular functions of CF discharge remain incompletely understood. In rat cerebellar slices, we show that CF discharge presented at physiological frequencies substantially modifies the frequency and pattern of Purkinje cell spike output in vitro. Repetitive CF discharge converts a spontaneous trimodal pattern of output characteristic of Purkinje cells in vitro to a more naturalistic nonbursting pattern consisting of spike trains interrupted by short CF-evoked pauses or longer pauses associated with state transitions. All effects of CF discharge could be reproduced in the presence of synaptic blockers by using current injections to simulate complex spike depolarizations, revealing that CF-evoked changes in Purkinje cell output can occur independently of network activation. Rather postsynaptic changes are sufficient to account for the CF-evoked block of trimodal activity and include at least the activation of Ca2+-dependent K+ channels. Furthermore by controlling the frequency of Purkinje cell spike output over three discrete firing levels, CF discharge modulates the gain of Purkinje cell responsiveness to PF inputs in vitro through postsynaptic mechanisms triggered by the complex spike depolarization. The ability for CF discharge to acutely modulate diverse aspects of Purkinje cell output provides important insights into the probable cellular factors contributing to motor disturbances following CF denervation.

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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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