Ion Channels Set Spike Timing Regularity of Mammalian Vestibular Afferent Neurons

Abstract

Kalluri R, Xue J, Eatock RA. Ion channels set spike timing regularity of mammalian vestibular afferent neurons. J Neurophysiol 104: 2034-2051, 2010. First published July 21, 2010 doi:10.1152/jn.00396.2010. In the mammalian vestibular nerve, some afferents have highly irregular interspike intervals and others have highly regular intervals. To investigate whether spike timing is determined by the afferents' ion channels, we studied spiking activity in their cell bodies, isolated from the vestibular ganglia of young rats. Whole cell recordings were made with the perforated-patch method. As previously reported, depolarizing current steps revealed distinct firing patterns. Transient neurons fired one or two onset spikes, independent of current level. Sustained neurons were more heterogeneous, firing either trains of spikes or a spike followed by large voltage oscillations. We show that the firing pattern categories are robust, occurring at different temperatures and ages, both in mice and in rats. A difference in average resting potential did not cause the difference in firing patterns, but contributed to differences in afterhyperpolarizations. A low-voltage-activated potassium current (I LV ) was previously implicated in the transient firing pattern. We show that I LV grew from the first to second postnatal week and by the second week comprised Kv1 and Kv7 (KCNQ) components. Blocking I LV converted step-evoked firing patterns from transient to sustained. Separated from their normal synaptic inputs, the neurons did not spike spontaneously. To test whether the firing-pattern categories might correspond to afferent populations of different regularity, we injected simulated excitatory postsynaptic currents at pseudorandom intervals. Sustained neurons responded to a given pattern of input with more regular firing than did transient neurons. Pharmacological block of I LV made firing more regular. Thus ion channel differences that produce transient and sustained firing patterns in response to depolarizing current steps can also produce irregular and regular spike timing.

Hyperpolarization-Activated Current (I h) in Vestibular Calyx Terminals: Characterization and Role in Shaping Postsynaptic Events

“…We therefore tested the effects of removing I h on the zero current potential, action potential, and EPSPs in calyces. In ruptured and perforated patch clamp recordings from vestibular primary neurons, spontaneous action potentials are not usually observed, however, action potentials have been evoked in whole-cell current clamp in calyces (Rennie and Streeter 2006;Dhawan et al 2010) and vestibular ganglion somata (Limón et al 2005;Risner and Holt 2006;Iwasaki et al 2008;Kalluri et al 2010). We evoked action potentials by delivering repeated hyperpolarizing current injections in current clamp and also observed spontaneous EPSPs between action potentials (Fig.…”

“…V 1/2 for I h in early postnatal (P5-P8) mouse primary vestibular ganglion cells averaged −110 mV (Chabbert et al 2001b), and we found a mean V 1/2 of −123 mV in control gerbil calyces. Therefore, I h is substantially activated at potentials more hyperpolarized than the mean resting potential, which averaged −61 mV in our isolated calyx terminals and −68 mV in vestibular ganglion neurons (Kalluri et al 2010). A Currents were simulated in response to a voltage protocol from a holding potential of -79 mV, followed by a 40-ms prepulse to −129 mV and subsequent test steps from −89 to +19 mV in 10-mV increments.…”

“…A Response of calyx terminal at rest and to a series of hyperpolarizing steps (25, 50, and 75 pA) from −61 mV with conductances as described in Table 2 vestibular afferents (Iwasaki et al 2008;Kalluri et al 2010). Vestibular ganglion neurons showed transient or sustained action potential responses following depolarizing current steps.…”

“…Vestibular ganglion neurons showed transient or sustained action potential responses following depolarizing current steps. Transient neurons in ganglion somata fired one or two action potentials to depolarizing current steps and may correspond to irregularly firing calyx afferents (Kalluri et al 2010). Sag responses occurred with hyperpolarizing current steps in current clamp, and the sag peak increased with increasing step size (Kalluri et al 2010).…”

“…Regularly firing afferents terminate in peripheral zones of vestibular sensory epithelia and irregularly firing afferents in more central zones (Goldberg 2000;Eatock and Songer 2011). Intrinsic membrane properties of afferent neurons may play an important role in determining firing pattern and ionic currents described in vestibular ganglion somata include voltage-and calcium-dependent K + currents (Chabbert et al 2001a;Limón et al 2005;Risner and Holt 2006;Iwasaki et al 2008;Kalluri et al 2010), sodium (Chabbert et al 1997) and calcium currents Chambard et al 1999;Autret et al 2005), and a mixed cation hyperpolarization-activated current (I h ) (Chabbert et al 2001b). Vestibular ganglion preparations lack peripheral dendritic terminals, but ionic conductances have also been described in the calyceal terminations of vestibular afferents (Hurley et al 2006;Rennie and Streeter 2006;Dhawan et al 2010;Meredith et al 2011).…”