Low‐voltage activated Kv1.1 subunits are crucial for the processing of sound source location in the lateral superior olive in mice

Abstract

Non-technical summary Voltage-gated potassium channels control excitability throughout the nervous system and their dysfunction (or mutation) is associated with epilepsy and movement disorders. Loss of the insulating myelin sheath around nerve fibres (axons) in multiple sclerosis causes transmission failure by exposing too many potassium channels. We show that too few potassium channels also causes errors in information transmission as measured by the ability to localize the source of a sound, and suggests a general role for potassium channels along myelinated nerve fibres. These results give insights into normal neuronal function and into neurodegenerative disease mechanisms for patients with ataxia and multiple sclerosis.Abstract Voltage-gated potassium (Kv) channels containing Kv1.1 subunits are strongly expressed in neurons that fire temporally precise action potentials (APs). In the auditory system, AP timing is used to localize sound sources by integrating interaural differences in time (ITD) and intensity (IID) using sound arriving at both cochleae. In mammals, the first nucleus to encode IIDs is the lateral superior olive (LSO), which integrates excitation from the ipsilateral ventral cochlear nucleus and contralateral inhibition mediated via the medial nucleus of the trapezoid body. Previously we reported that neurons in this pathway show reduced firing rates, longer latencies and increased jitter in Kv1.1 knockout (Kcna1 −/− ) mice. Here, we investigate whether these differences have direct impact on IID processing by LSO neurons. Single-unit recordings were made from LSO neurons of wild-type (Kcna1 +/+ ) and from Kcna1 −/− mice. IID functions were measured to evaluate genotype-specific changes in integrating excitatory and inhibitory inputs. In Kcna1 +/+ mice, IID sensitivity ranged from +27 dB (excitatory ear more intense) to −20 dB (inhibitory ear more intense), thus covering the physiologically relevant range of IIDs. However, the distribution of IID functions in Kcna1 −/− mice was skewed towards positive IIDs, favouring ipsilateral sound positions. Our computational model revealed that the reduced performance of IID encoding in the LSO of Kcna1 −/− mice is mainly caused by a decrease in temporal fidelity along the inhibitory pathway. These results imply a fundamental role for Kv1.1 in temporal integration of excitation and inhibition during sound source localization.

Genetic perturbations suggest a role of the resting potential in regulating the expression of the ion channels of the KCNA and HCN families in octopus cells of the ventral cochlear nucleus

“…The relatively sluggish g h helps give auditory neurons a low input resistance that makes voltage changes rapid while the speedy g KL repolarizes not only suprathreshold but also subthreshold synaptic potentials (Oertel, 1983; Manis and Marx, 1991; Brew and Forsythe, 1995; Golding et al, 1995; Rathouz and Trussell, 1998; Dodson et al, 2002; Ferragamo and Oertel, 2002; Barnes-Davies et al, 2004; Rothman and Manis, 2003a; Brew et al, 2003; Kuba et al, 2005; Brew and Forsythe, 2005; Scott et al, 2005; Gittelman and Tempel, 2006; McGinley and Oertel, 2006; Mathews et al, 2010; Karcz et al, 2011; Khurana et al, 2011; Golding and Oertel, 2012). …”

Dopaminergic projections of the subparafascicular thalamic nucleus to the auditory brainstem

“…After locating the SPN, we found the MNTB by shifting the electrode medially and identifying primary-like spiking patterns that produced stronger responses to contralateral stimulation (Kopp-Scheinpflug et al, 2003). We found the LSO by shifting the electrode laterally from the SPN and identifying chopper-like patterns that produced stronger responses to ipsilateral stimulation (Adam et al, 1999; Karcz et al, 2011). The tracers were deposited using current (7s on/7s off) of 4 μA for 5–10 minutes.…”

Modulation and control of synaptic transmission across the MNTB

“…Nodal sodium channels (Na V 1.6; Leao et al, 2005) are complimented by nodal Kv3.1 potassium channels (Devaux et al, 2003;Vacher et al, 2008) and juxtaparanodal Kv1 potassium channels (Wang et al, 1993;Rasband, 2004;Karcz et al, 2011). In patchclamp recordings from the calyx of Held, Kv1 and Kv3 currents are present (Forsythe, 1994;Dodson et al, 2003;Ishikawa et al, 2003) and serve similar functions as the same channels in the postsynaptic MNTB neuron, with Kv1 channels suppressing excitability during the depolarizing after-potential which follows each presynaptic AP and Kv3 being involved in AP repolarization (Wang et al, 1998).…”