HCN channels segregate stimulation-evoked movement responses in neocortex and allow for coordinated forelimb movements in rodents

Abstract

The mechanisms by which distinct movements of a forelimb are generated from the same area of motor cortex have remained elusive. Here we examined a role for HCN channels, given their ability to alter synaptic integration, in the expression of forelimb movement responses during intracortical microstimulation (ICMS) and movements of the forelimb on a skilled reaching task. We used short-duration high resolution ICMS to evoke forelimb movements following pharmacological (ZD7288), experimental (electrically induced cortical seizures) or genetic approaches that we confirmed with whole-cell patch clamp to substantially reduce I_h current. We observed significant increases in the number of multiple movement responses evoked at single sites in motor maps to all 3 experimental manipulations in rats or mice. HCN1^KO mice were less successful and exhibited atypical movements on a skilled-motor learning task relative to wild-type controls. Furthermore, in reaching-proficient rats, reaching accuracy was reduced and forelimb movements were altered during infusion of ZD7288 within motor cortex. Thus, HCN channels play a critical role in the separation of overlapping movement responses and allow for successful reaching behaviours. These data provide a novel mechanism for the encoding of multiple movement responses within shared networks of motor cortex. This mechanism supports a viewpoint of primary motor cortex as a site of dynamic integration for behavioural output.

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