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

E. De Schutter, J. M. Bower

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

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 Ca2+-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 interspike 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. In addition, changes in inhibitory frequency caused a parallel shift of the relationship between excitatory input and spiking frequency. Because of the specific cerebellar circuitry, inhibitory inputs may allow Purkinje cells to detect small fluctuations in excitatory input at any mean frequency of input. 6. When climbing fiber input was given in the presence of background asynchronous excitatory and inhibitory inputs the shape of the complex spike in the soma was significantly affected. However, the shape of the spike in the dendrites was almost constant. This difference reflected the more variable excitability of the soma compared with the dendrites. 7. Synchronous activation of basket cell inhibitory synapses during asynchronous activation of granule and stellate cell synapses interrupted somatic spiking. However, the hyperpolarization caused by the basket cell synapse did not penetrate far into the dendrite but stayed localized to the soma and main dendrite. 8. This simulation work demonstrates that a model based on voltage-clamp data and tuned entirely on the response of Purkinje cells to current injection is capable of reproducing a wide range of synaptically activated responses. In the presence of continuous granule cell excitation the model showed a stable in vivo state different from the silent, resting in vitro state. Further, the model suggests that there may be important functional interactions between different types of synaptic inputs. In particular, it makes several specific predictions about the role of stellate cell inhibition.

Original languageEnglish (US)
Pages (from-to)401-419
Number of pages19
JournalJournal of Neurophysiology
Volume71
Issue number1
StatePublished - 1994
Externally publishedYes

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Purkinje Cells
Synapses
Dendrites
Membranes
Carisoprodol
Action Potentials
Calcium-Activated Potassium Channels
Sodium
Injections

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

An active membrane model of the cerebellar Purkinje cell II. Simulation of synaptic responses. / De Schutter, E.; Bower, J. M.

In: Journal of Neurophysiology, Vol. 71, No. 1, 1994, p. 401-419.

Research output: Contribution to journalArticle

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