Firing frequency and entrainment maintained in primary auditory neurons in the presence of combined BDNF and NT3

Abstract

Primary auditory neurons rely on neurotrophic factors for development and survival. We previously determined that exposure to brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) alters the activity of hyperpolarization-activated currents (Ih) in this neuronal population. Since potassium channels are sensitive to neurotrophins, and changes in Ih are often accompanied by a shift in voltage-gated potassium currents (IK), this study examined IK with exposure to both BDNF and NT3 and the impact on firing entrainment during high frequency pulse trains. Whole-cell patch-clamp recordings revealed significant changes in action potential latency and duration, but no change in firing adaptation or total outward IK. Dendrotoxin-I (DTX-I), targeting voltage-gated potassium channel subunits KV1.1 and KV1.2, uncovered an increase in the contribution of DTX-I sensitive currents with exposure to neurotrophins. No difference in Phrixotoxin-1 (PaTX-1) sensitive currents, mediated by KV4.2 and KV4.3 subunits, was observed. Further, no difference was seen in firing entrainment. These results show that combined BDNF and NT3 exposure influences the contribution of KV1.1 and KV1.2 to the low voltage-activated potassium current (IKL). Whilst this is accompanied by a shift in spike latency and duration, both firing frequency and entrainment to high frequency pulse trains are preserved.

Hybrid optogenetic and electrical stimulation for greater spatial resolution and temporal fidelity of cochlear activation

“…Poststimulus facilitation in single auditory neurons extended to delays of 9-13 ms between the optical and electrical stimuli in vitro, which is greater than the facilitation observed in vivo. Dynamics and firing rates are generally slower in vitro, as found previously for electrical stimulation (Wright et al, 2016). Despite these differences, the observed facilitation both in vitro and in vivo suggests that cultured SGNs are a good in vitro model for hybrid optical stimulation.…”

Identification of Persistent and Resurgent Sodium Currents in Spiral Ganglion Neurons Cultured from the Mouse Cochlea

“…Recordings from individual SGNs in mice have demonstrated peak discharge rates >1 kHz ( Taberner and Liberman, 2005 ), which then adapt to steady state levels >200 Hz, suggesting these neurons employ specialized mechanisms that support repetitive rapid spiking and ensure extremely short refractory periods. Patch clamp recordings and immuno-labeling experiments have suggested that the expression of numerous ion channel subtypes contributes to shaping the firing properties of SGNs, in mice and rats ( Jagger and Housley, 2002, 2003 ; Hossain et al, 2005 ; Wang et al, 2013 ; Crozier and Davis, 2014 ; Smith et al, 2015 ; Kim and Rutherford, 2016 ; Wright et al, 2016 ), and in guinea pigs ( Santos-Sacchi, 1993 ; Szabó et al, 2002 ). Following hearing onset, increases in firing rates and shortening of the refractory period are observed ( Wu et al, 2016 ).…”

Improving Control of Gene Therapy-Based Neurotrophin Delivery for Inner Ear Applications

“…A wide variety of growth factors in the inner ear can potentially improve the performance of cochlear implants based on animal models of cochlear implantation. The effect of growth factor infusion into the deaf inner ear can include enhancing the survival of neurons as well as all enhancing and altering the capacity for depolarization of the neurons (Wright et al, 2016). Translation of these observations into successful human studies will require understanding the pathophysiology of neuronal degeneration in human spiral ganglion cells as well as developing systems that restore physiologically relevant levels of growth factors to the inner ear.…”