Neuronal Mechanisms Underlying HCN1-Dependent Motor Behavior Deficits

Abstract

Molecular mechanisms that configure neuronal responses to synaptic input are critical for coordinated behavior. Evidence from mice with global deletion of the HCN1 gene, which encodes hyperpolarization-activated cyclic nucleotide-gated (HCN) channels with rapid kinetics, suggests that this channel is important for synaptic integration underlying learned motor behaviors. We have shown earlier that HCN1 channels control the waveform of responses of neurons in the inferior olive to long-range synaptic input. But how does this affect inferior olive output, cerebellar output, and consequently cerebellar-dependent behavior? To address the neuronal mechanism by which HCN1 channels might influence motor behavior, I made cell-attached patch clamp recordings from cerebellar Purkinje cells in awake behaving mice with a global deletion of the HCN1 channel. I show that HCN1 channels affect neuronal firing patterns and complex spike waveforms, and next investigated how these specific changes affect motor behavior.