Intrinsic Plasticity of Cerebellar Purkinje Cells




Yang, Zhen

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Coding in cerebellar Purkinje cells not only depends on synaptic plasticity but also on their intrinsic membrane excitability. We performed whole cell patch-clamp recordings of Purkinje cells in sagittal cerebellar slices in mice. We found that inducing long-term depression (LTD) in the parallel fiber to Purkinje cell synapses results in an increase in the gain of the firing rate response. This increase in excitability is accompanied by an increase in the input resistance and a decrease in the amplitude of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel mediated voltage sag. Application of a HCN channel blocker prevents the increase in input resistance and excitability without blocking the expression of synaptic LTD. We conclude that the induction of parallel fiber-Purkinje cell LTD is accompanied by an increase in excitability of Purkinje cells through downregulation of the HCN mediated h current. We suggest that HCN downregulation is linked to the biochemical pathway that sustains synaptic LTD. Given the diversity of information carried by the parallel fiber system, we suggest that changes in intrinsic excitability enhance the coding capacity of the Purkinje cell to specific input sources.

To further explore the impact of synaptic plasticity induction on calcium dynamics in cerebellar Purkinje cells, we measured the changes in intracellular calcium in response to climbing fiber stimulation before and after induction of LTD in the parallel fiber synapse. We found that the calcium response to climbing fiber activation increases in the region near and around the induction site of LTD while dendritic regions far from the site of conditioning are not affected. Furthermore, the changes in calcium response after LTD induction are localized in spiny dendrites, but not in smooth main dendrites, even when they are in close vicinity to conditioning sites. Thus, our results show that the climbing fiber evoked calcium response increases in spiny dendrites around the presumed synaptic LTD induction site. Given the dependence of synaptic plasticity on calcium concentration, this could facilitate synapses that underwent LTD to reach the threshold for further synaptic plasticity.


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Integrative Biology