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

Karcz, Anita; Hennig, Matthias H.; Robbins, Carol A.; Tempel, Bruce L.; Rübsamen, Rudolf und Kopp-Scheinpflug, Conny (2011): Low-voltage activated Kv1.1 subunits are crucial for the processing of sound source location in the lateral superior olive in mice. In: Journal of Physiology, Bd. 589, Nr. 5: S. 1143-1157

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.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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Biologie > Department Biologie II > Neurobiologie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften; Biologie
• ISSN: 0022-3751
• Sprache: Englisch