Hyperpolarization-activated currents are differentially expressed in mice brainstem auditory nuclei

The hyperpolarization-activated cation current (I_h) may influence precise auditory processing by modulating resting membrane potential and cell excitability. We used electrophysiology and immunohistochemistry to investigate the properties of I_h in three auditory brainstem nuclei in mice: the anteroventral cochlear nucleus (AVCN), the medial nucleus of the trapezoid body (MNTB) and the lateral superior olive (LSO). I_h amplitude varied considerably between these cell types, with the order of magnitude LSO > AVCN > MNTB. Kinetically, I_h is faster in LSO neurons, and more active at rest, compared with AVCN and MNTB cells. The half-activation voltage is - 10 mV more hyperpolarized for AVCN and MNTB cells compared with LSO neurons. HCN1 immunoreactivity strongly labelled AVCN and LSO neurons, while HCN2 staining was more diffuse in all nuclei. The HCN4 subunit displayed robust membrane staining in AVCN and MNTB cells but weak labelling of the LSO. We used a dynamic clamp, after blocking I_h, to reinsert I_h to the different cell types. Our results indicate that the native I_h for each cell type influences the resting membrane potential and can delay the generation of action potentials in response to injected current. Native I_h increases rebound depolarizations following hyperpolarizations in all cell types, and increases the likelihood of rebound action potentials (particularly in multiple-firing LSO neurons). This systematic comparison shows that I_h characteristics vary considerably between different brainstem nuclei, and that these differences significantly affect the response properties of cells within these nuclei.