Purkinje cell intrinsic excitability increases after synaptic long term depression

Area of Science:

• Neuroscience
• Cellular Electrophysiology
• Synaptic Plasticity

Background:

• Cerebellar Purkinje cell function relies on both synaptic plasticity and intrinsic membrane excitability.
• Understanding how these properties interact is crucial for deciphering neural coding mechanisms.

Purpose of the Study:

• To investigate the impact of inducing long-term depression (LTD) at parallel fiber-Purkinje cell synapses on Purkinje cell intrinsic excitability.
• To identify the specific ion channels involved in LTD-induced changes in Purkinje cell excitability.

Main Methods:

• Whole-cell patch-clamp recordings were performed on Purkinje cells in mouse cerebellar slices.
• Long-term depression (LTD) was induced at parallel fiber synapses.
• The effects of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers were assessed.

Main Results:

• Induction of LTD increased Purkinje cell firing rate gain, input resistance, and decreased HCN channel-mediated voltage sag.
• Blocking HCN channels prevented the LTD-induced increase in excitability without affecting LTD expression.
• LTD induction leads to downregulation of the HCN-mediated h current.

Conclusions:

• Parallel fiber-Purkinje cell LTD increases Purkinje cell excitability via downregulation of the HCN-mediated h current.
• HCN channel downregulation is linked to the biochemical pathways sustaining synaptic LTD.
• Altered intrinsic excitability enhances Purkinje cell coding capacity for specific inputs.