Hyperpolarization‐activated (I_h) currents in auditory brainstem neurons of normal and congenitally deaf mice

Abstract

We have investigated the membrane properties of brainstem auditory neurons in a mouse model of congenital deafness (dn ⁄ dn). Whole-cell recordings were made from visualized neurons in slices of the medial nucleus of the trapezoid body (MNTB) and anteroventral cochlear nucleus (AVCN). We have recently demonstrated that MNTB neurons in deaf mice are more excitable than in normal mice, due in part to a reduced expression of low-threshold potassium currents. In this study, we have examined the contribution of hyperpolarization-activated (I h ) channels to the membrane properties of MNTB and AVCN neurons. Our results show that I h is larger in MNTB neurons from deaf mice than in normal mice. In contrast, no significant differences were found in I h or excitability between AVCN bushy cells from dn ⁄ dn and normal mice. Experimental evidence and neuronal modelling suggests that, in the MNTB of normal mice, a small contribution of I h helps to reduce temporal summation of synaptic potentials. A larger I h in neurons from deaf mice has a much greater effect in reducing temporal summation of synaptic potentials, counteracting to some extent the greater excitability of these cells. Our results provide further insight into the role of activity during development in regulating the membrane and firing properties of central neurons.

P2 Receptor–Mediated Signaling in Spherical Bushy Cells of the Mammalian Cochlear Nucleus

“…1, Ac and Bc), consistent with type II discharge pattern of AVCN bushy cells (Francis and Manis 2000;Oertel 1983;Wu and Oertel 1984). As in previous studies on bushy cells in gerbil and mice (Cao et al 2007;Leao et al 2005;Schwarz and Puil 1997), hyperpolarizing current pulses produced voltage changes that sagged back toward rest caused by hyperpolarization-activated conductances, and anode-break action potentials occurred after the pulse offset. Biocytin labeling of recorded cells showed the morphological features of large spherical bushy cells which occupy the anterior pole of the AVCN in low frequency hearing animals (Bazwinsky et al Ostapoff et al 1994;Rouiller and Ryugo 1984;Ryugo and Sento 1991).…”

Spontaneous activity in the developing auditory system

“…This aberrant Cl − homeostasis prevents the shift of GABA/glycinergic responses from depolarizing to hyperpolarizing, and disrupts inhibition of neurons in lateral superior olive (LSO) and IC (Kotak and Sanes 1996;Sanes 2000, 2002;Vale et al 2003). Moreover, principal neurons of the MNTB in congenitally deaf dn/dn mouse show enhanced excitability and non-synchronized firing in response to synaptic inputs (Leao et al 2004a(Leao et al , 2005(Leao et al , 2006a, and lose their gradient in expression of ion channels along the tonotopic axis (Leao et al 2006b). The firing properties and channel expression of LSO neurons also are altered in congenitally deaf mouse lines (Couchman et al 2011;Hirtz et al 2011), providing further indication that lack of peripheral excitatory drive disrupts the physiological maturation of central auditory neurons.…”

Kv7/KCNQ Channels Control Action Potential Phasing of Pyramidal Neurons during Hippocampal Gamma OscillationsIn Vitro

“…and the third-order coefficient a used as a measure of the histogram "peakedness" (AP synchronicity or randomness (Leao et al, 2005). To block the native I M of single cells we supplemented our internal solution with 0.5 mM BaCl 2 (Lamas et al, 1997).…”