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

Abstract

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.

Repertoire of high voltage-activated Ca2+ channels in the lateral superior olive: functional analysis in wild-type, Cav1.3−/−, and Cav1.2DHP−/− mice

“…As we used a Cs-based intracellular solution, we could not use criteria like firing pattern, resting membrane potential, K ϩ -mediated outward currents, or hyperpolarization-activated inward currents for cell identification. Nevertheless, our whole cell capacitance values are in very good accord with data from mouse and rat principal LSO neurons (Barnes-Davies et al 2004;Dodson et al 2002;Leao et al 2006;Sterenborg et al 2010). We therefore conclude that our recordings originated from principal cells and thus from a homogenous population.…”

Comparative posthearing development of inhibitory inputs to the lateral superior olive in gerbils and mice

“…We characterized the membrane properties of principal neurons in mice and gerbil LSO in response to hyper-and depolarizing current injections. The intrinsic properties of LSO principal neurons have been reported to differ among various species in terms of firing pattern, input resistance, and membrane potential changes upon hyperpolarization (Adam et al 2001;Adam et al 1999;Barnes-Davies et al 2004;Hassfurth et al 2009;Kandler and Friauf 1995;Leao et al 2006;Sanes 1993). However, these studies were carried out under different conditions, such as various compositions of ACSFs and electrode solutions and different temperatures and ages of animals.…”

“…However, one has also to consider that these studies were performed at different developmental stages and under various experimental conditions. It is generally known that the major ion channels that determine the intrinsic membrane properties of LSO neurons, namely various K-channels and the hyperpolarization-activated cyclic nucleotide-gated channels, can be modulated by neuronal activity via the activation and deactivation of second messengers, or can be affected by the composition of the electrode solution, or by recording conditions such as temperature (Leao et al 2006). Fig.…”

Combined application of brain-derived neurotrophic factor and neurotrophin-3 and its impact on spiral ganglion neuron firing properties and hyperpolarization-activated currents

“…HCN channels and I h have previously been shown to play an important role in shaping the activity of auditory neurons (Bal and Oertel, 2000;Banks et al, 1993;Chen, 1997;Cuttle et al, 2001;Leao et al, 2011Leao et al, , 2006Leao et al, , 2005Rodrigues and Oertel, 2006;Yamada et al, 2005;Yi et al, 2010). This current has also been linked to functional changes in hearing loss (Hassfurth et al, 2009).…”