Kv1 currents mediate a gradient of principal neuron excitability across the tonotopic axis in the rat lateral superior olive

Within the Ca v 1 family of voltage-gated calcium channels, Ca v 1.2 and Ca v 1.3 channels are the predominant subtypes in the brain. Whereas specific functions for each subtype were described in the adult brain, their role in brain development is poorly understood. Here we assess the role of Ca v 1.3 subunits in the activity-dependent development of the auditory brainstem. We used Ca v 1.3-deficient (Ca v 1.3 Ϫ/Ϫ ) mice because these mice lack cochlea-driven activity that deprives the auditory centers from peripheral input. We found a drastically reduced volume in all auditory brainstem centers (range 25-59%, total 35%), which was manifest before hearing onset. A reduction was not obvious outside the auditory system. The lateral superior olive (LSO) was strikingly malformed in Ca v 1.3 Ϫ/Ϫ mice and had fewer neurons (1/3 less). The remaining LSO neurons displayed normal dendritic trees and received functional glutamatergic input, yet they fired action potentials predominantly with a multiple pattern upon depolarization, in contrast to the single firing pattern prevalent in controls. The latter finding appears to be due to a reduction of dendrototoxin-sensitive potassium conductances, presumably mediated through the K v 1.2 subtype. Fura2 imaging provided evidence for functional Ca v 1.3 channels in the LSO of wild-type mice. Our results imply that Ca v 1.3 channels are indispensable for the development of the central auditory system. We propose that the unique LSO phenotype in Ca v 1.3 Ϫ/Ϫ mice, which hitherto was not described in other hereditary deafness models, is caused by the synergistic contribution of two factors: on-site loss of Ca v 1.3 channels in the neurons plus lack of peripheral input.

Section: Changes In Action Potential Properties and Current-voltage Rsupporting

confidence: 87%

Ca_v1.3 Calcium Channels Are Required for Normal Development of the Auditory Brainstem

Hirtz

Boesen²,

Braun³

et al. 2011

“…In NM of the chicken, the monotonic gradient of the expression of both mRNA and protein of Kv1.1, as well as the DTX-sensitive current were found, increasing toward the high-CF region (Fukui and Ohmori, 2004). In the lateral superior olive of the rat (Barnes-Davies et al, 2004), neurons in the low-CF region expressed higher levels of Kv1 channels than those in the high-CF region, which allows the low-CF neurons to integrate precisely timed binaural signals.…”

Section: Tonotopic Specialization Of Lowthreshold Kmentioning

confidence: 94%

Tonotopic Specialization of Auditory Coincidence Detection in Nucleus Laminaris of the Chick

Kuba

Yamada²,

Fukui³

et al. 2005

113

145

The interaural time difference (ITD) is a cue for localizing a sound source along the horizontal plane and is first determined in the nucleus laminaris (NL) in birds. Neurons in NL are tonotopically organized, such that ITDs are processed separately at each characteristic frequency (CF). Here, we investigated the excitability and coincidence detection of neurons along the tonotopic axis in NL, using a chick brainstem slice preparation. Systematic changes with CF were observed in morphological and electrophysiological properties of NL neurons. These properties included the length of dendrites, the input capacitance, the conductance of hyperpolarization-activated current, and the EPSC time course. In contrast to these gradients, the conductance of low-threshold K ϩ current and the expression of Kv1.2 channel protein were maximal in the central (middle-CF) region of NL. As a result, the middle-CF neuron had the smallest input resistance and membrane time constant, and consequently the fastest EPSP, and exhibited the most accurate coincidence detection. The specialization of middle-CF neurons as coincidence detectors may account for the high resolution of sound-source localization in the middle-frequency range observed in avians.

“…Thus, different membrane excitability among NM neurons is probably created by the graded expression of Kv1.1. In LSO principal neuron, Kv1 channels underlie the gradient of firing properties of single spiking neurons (Barnes-Davies et al, 2004). It is likely that the gradient of Kv1.1 may reflect some graded dominance of heteromeric composition of Kv1.1 and Kv1.2 along the tonotopic axis.…”

Section: Expression Of Dtx-sensitive Currentsmentioning

confidence: 99%

“…Large EPSCs are reported in NM neurons, which reduce the temporal jitter for spike generation to 20 sec (Brenowitz and Trussell, 2001). In rat, immunolabeling to Kv1.1 showed a gradient across the tonotopic axis in the lateral superior olive (LSO), which underlies the firing properties of principal neuron (Barnes-Davies et al, 2004). However, tonotopic gradient of Kv1.1 protein was not clearly demonstrated in the NM of the chicken (Lu et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Tonotopic Gradients of Membrane and Synaptic Properties for Neurons of the Chicken Nucleus Magnocellularis

Fukui¹,

Ohmori²

2004

144

Nucleus magnocellularis (NM) is a division of the avian cochlear nucleus that extracts the timing of auditory signals. We compared the membrane excitability and synaptic transmission along the tonotopic axis of NM. Neurons expressed a Kv1.1 potassium channel mRNA and protein predominantly in the high characteristic frequency (CF) region of NM. In contrast, the expression of Kv1.2 mRNA did not change tonotopically. Neurons also showed tonotopic gradients in resting potential, spike threshold, amplitude, and membrane rectification. All neurons were sensitive to 100 nM dendrotoxin, but the effects were most significant in the high CF neurons. The EPSC recorded by minimal stimulation of auditory nerve fibers (ANFs) was 13 times larger in high CF neurons than in low CF neurons. Moreover, EPSCs were generated in an all-or-none manner in the high CF neurons when stimulus intensity was increased, whereas EPSCs were graded in the low CF neurons, indicating multiple axonal inputs. ANF synaptic terminals were visualized by DiI. ANF formed enfolding end-bulbs of Held around the cell body in the high and middle CF region but not in the low CF region. These observations indicate coordinated gradients of neuronal properties both presynaptically and postsynaptically along the tonotopic axis. Such specializations may be suitable for extracting and preserving the timing information of auditory signals over a wide range of acoustic frequencies.