Purkinje cell intrinsic excitability increases after synaptic long term depression.
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.
UTSA Neurosciences Institute and Department of Biology, University of Texas at San Antonio, San Antonio, Texas.
Zhen
Z
Yang
UTSA Neurosciences Institute and Department of Biology, University of Texas at San Antonio, San Antonio, Texas Fidel.santamaria@utsa.edu.
Fidel
0000-0001-8750-2932
F
Santamaria
D000818:Animals; D015536:Down-Regulation / Q000502:physiology; D017097:Electric Impedance; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000378:metabolism; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D046509:Tissue Culture Techniques
D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
cerebellar function; dendritic integration; memory; synaptic throughput