HCN

HCN or hyperpolarization-activated, cyclic-nucleotide gated, cation nonselective channels play a role in regulating neuronal electrical activity. The channels are gated by a chemical ligand (the cyclic nucleotide; e.g. cAMP or cGMP), but have a more structure similar to voltage-gated ion channels than to the ligand-gated channels. They often have +/- charged areas that respond to changes in membrane potential.

I_h is a mixed cation current that typically activates with hyperpolarizing steps to potentials negative to -60 mV.

Physiological Expression

HCN1 are expressed at high levels in Purkinje and basket cells of the cerebellar cortex, which suggest a possible role in cerebellar learning. Hyperpolarzation-activated currents (I_h ) have been recorded from these cerebellar Purkinje neurons and basket cells; however, it is not clear how I_h potentials such as pacemaking of spontaneous action potential firing, waveform shaping of dendritic synaptic potentials, or preventing membrane potential bistability may contribute to motor learning.

Neural Correlates to Behavior

The role of HCN1 in regulating motor learning has been investigated by several groups of researchers including Nolan, Siegelbaum, Kandel, et al. (2003) where they explore the HCN1 subunit's function in motor learning using generalized and regional knockouts. In one mouse line, the HCN1 channel was knocked out in all cells; in the other line, HCN1 was knocked out in the forebrain only. The former of the two lines allowed them to study the function of HCN1 in motor learning, and the latter in Purkinje cells (which are the sole output of the cerebellum).

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