Opposite Actions of Brain-Derived Neurotrophic Factor and Neurotrophin-3 on Firing Features and Ion Channel Composition of Murine Spiral Ganglion Neurons

Abstract

It is now well established that sensory neurons and receptors display characteristic morphological and electrophysiological properties tailored to their functions. This is especially evident in the auditory system, where cells are arranged tonotopically and are highly specialized for precise coding of frequency-and timing-dependent auditory information. Less well understood, however, are the mechanisms that give rise to these biophysical properties. We have provided insight into this issue by using whole-cell current-clamp recordings and immunocytochemistry to show that BDNF and NT-3, neurotrophins found normally in the cochlea, have profound effects on the firing properties and ion channel distribution of spiral ganglion neurons in the murine cochlea. Exposure of neurons to BDNF caused all neurons, regardless of their original cochlear position, to display characteristics of the basal neurons. Conversely, NT-3 caused cells to show the properties of apical neurons. These results are consistent with oppositely oriented gradients of these two neurotrophins and/or their high-affinity receptors along the tonotopic map, and they suggest that a combination of neurotrophins are necessary to establish the characteristic firing features of postnatal spiral ganglion neurons.

Unmasking of Spiral Ganglion Neuron Firing Dynamics by Membrane Potential and Neurotrophin-3

“…7D) from P6 to P14 (NT-3 exposed: P6, Ϫ47.2 Ϯ 1.4 mV; P8, Ϫ48.9 Ϯ 1.0 mV; P10, Ϫ47.4 Ϯ 1.0 mV; P14, Ϫ46.9 Ϯ 0.8 mV; see figure for statistical comparisons). In contrast to basal neurons, apical neurons responded less robustly across all ages, which is consistent with a previous report (Adamson et al, 2002a; see figure legend for details). The effects of NT-3 on basal neurons suggest that timing features such as latency and APmax (which may be a mixture of timing and excitability) are regulated differently than voltage threshold in response to trkC activation.…”

“…The data in Figure 2 provide an analysis of rate/level functions to illustrate the wide dynamic range of spiral ganglion neuron firing properties. Representative current-clamp recordings, chosen to illustrate the breadth of individual response profiles, were categorized as described previously Adamson et al, 2002a) and based on Figure 1, RA or SA. These recordings were characterized according to the number of APs elicited over a large voltage range (RA, Fig.…”

“…Nevertheless, voltage-gated Ca 2ϩ channels are candidates for maintaining a stable firing rate due to their role in regulating both AP latency and duration (Chen et al, 2011). Although most voltage-gated ion channels evaluated in the spiral ganglion show tonotopic gradations and, therefore, are likely regulated by NT-3 and BDNF (Adamson et al, 2002a), one channel type, Ca v 2.2, stands out because it is distributed uniformly throughout the ganglion (Chen et al, 2011). Furthermore, because Ca v 2.2 channels are high-voltage activated, they may be less sensitive to differences in voltage threshold.…”

Temporary Neurotrophin Treatment Prevents Deafness-Induced Auditory Nerve Degeneration and Preserves Function

“…A possible mechanism by which BDNF might cause changes in SGC function is modulation of voltage-gated ion channel expression, distribution, and activity. In in vitro experiments, Adamson et al (2002) showed that redistribution of ion channels causes basal SGCs to exhibit apical firing properties (sustained firing) after NT-3 treatment and apical SGCs to display basal firing properties (phasic firing) after BDNF treatment. It is therefore possible that the eCAP changes we observed in BDNF-treated cochleas reflected a more "basal" composition of the SGC population.…”

“…The transient BDNF-induced increase in SGC size may initially affect temporal responsiveness because membrane capacitance is linearly related to soma diameter (Limó n et al, 2005). Additionally, because BDNF treatment causes apical neurons to change from continuously firing to rapidly adapting under constant depolarization (Adamson et al, 2002), slower recovery arguably is a logical consequence of BDNF treatment.…”