Hyperpolarization activated cation channels of the HCN gene family such as HCN1, contribute to spontaneous rhythmic activity in both heart and brain. HCN1 is a member of a family of pacemaker channels activated by hyperpolarisation and regulated by cyclic nucleotides. HCN1 and HCN2 play an important role for motor learning and neuronal integration by cerebellar Purkinje cells; as well as, shaping autonomous activity of single neurons and the periodicity of network oscillations. HCN1 expression is highly enriched in cerebral cortex, hippocampus, cerebellum, and facial motor nucleus. HCN2 is highly abundant in mamillary bodies, pontine nucleus, ventral cochlear nucleus, and nucleus of the trapezoid body. These variations in regional specificity of HCN channels could generate important differences in neuronal pacemaker activity across brain systems.