Diverse levels of an inwardly rectifying potassium conductance generate heterogeneous neuronal behavior in a population of dorsal cochlear nucleus pyramidal neurons

Abstract

Leao RM, Li S, Doiron B, Tzounopoulos T. Diverse levels of an inwardly rectifying potassium conductance generate heterogeneous neuronal behavior in a population of dorsal cochlear nucleus pyramidal neurons. J Neurophysiol 107: 3008 -3019, 2012. First published February 29, 2012 doi:10.1152/jn.00660.2011.-Homeostatic mechanisms maintain homogeneous neuronal behavior among neurons that exhibit substantial variability in the expression levels of their ionic conductances. In contrast, the mechanisms, which generate heterogeneous neuronal behavior across a neuronal population, remain poorly understood. We addressed this problem in the dorsal cochlear nucleus, where principal neurons exist in two qualitatively distinct states: spontaneously active or not spontaneously active. Our studies reveal that distinct activity states are generated by the differential levels of a Ba 2ϩ -sensitive, inwardly rectifying potassium conductance (K ir ). Variability in K ir maximal conductance causes variations in the resting membrane potential (RMP). Low K ir conductance depolarizes RMP to voltages above the threshold for activating subthresholdpersistent sodium channels (Na p ). Once Na p channels are activated, the RMP becomes unstable, and spontaneous firing is triggered. Our results provide a biophysical mechanism for generating neural heterogeneity, which may play a role in the encoding of sensory information. auditory; neural heterogeneity; potassium channels; spontaneous firing THEORETICAL AND EXPERIMENTAL work has revealed that similar circuit and neuronal function can result from substantially different combinations of correlated and compensating intrinsic and synaptic conductances Marder and Goaillard 2006;Prinz et al. 2004). In accordance with this view, recent studies have shown that variability in one or more conductances is accompanied by coordinated compensatory variations in other conductances, which maintain constant neuronal behavior (Achard and De Schutter 2006;Cao and Oertel 2011;Goldman et al. 2001;Golowasch et al. 2002;Grashow et al. 2010;Schulz et al. 2006Schulz et al. , 2007Sobie 2009;Swensen and Bean 2005;Taylor et al. 2009;Tobin and Calabrese 2006). These homeostatic mechanisms involve coordinated changes in channel densities, which push or pull excitability toward opposite directions, so that intrinsic variability produces an equivalent output response (MacLean et al. 2003;Schulz et al. 2006). However, less is known about mechanisms that generate a heterogeneous output response within a neuronal population. To answer this question, we studied the cellular mechanisms underlying neural heterogeneity in dorsal cochlear nucleus (DCN) principal neurons. Numerous in vitro and in vivo studies in anaesthetized and in awake animals have shown that each DCN principal neuron (fusiform cells) exists in one of two qualitatively distinct intrinsic states: a quiet state, where the membrane potential settles at a resting membrane potential (RMP) value, or a spontaneously active state, where action potentials (APs) are spon...

Control of Interneuron Firing by Subthreshold Synaptic Potentials in Principal Cells of the Dorsal Cochlear Nucleus

“…Membrane potential in CsCl + bias current condition: −70.0±1.4 mV). The voltage-dependent drop in membrane resistance is likely due to activation of inward rectifier K + conductance, as described previously (Leao et al, 2012). In agreement with a HCN-mediated mechanism, CsCl blocked the AHP following aEPSPs (n=7, Figure 3A+inset).…”

“…Given that fusiform cells express a long-lasting Na + current that is active at subthreshold voltages (Leao et al, 2012), we hypothesized that subthreshold excitation might activate this current and broaden parallel fiber-fusiform cell EPSPs. If so, the slow inward component observed in stellate cells (Figure 1B) would not merely represent a passive depolarization of fusiform cell dendrites during EPSPs, but rather an active subthreshold depolarization by Na + currents in prejunctional fusiform cells.…”

The role of negative conductances in neuronal subthreshold properties and synaptic integration

“…Similar results were obtained by Hirsch and Oertel (1988) in fusiform cells of the dorsal cochlear nucleus of mice where a TTXsensitive increase in R m with depolarization was observed. These authors also observed a concomitant decrease in R m and τ m with hyperpolarization, in parallel with the deactivation of I NaP which is present in these neurons (Leao et al 2012).…”

Pathogenic plasticity of Kv7.2/3 channel activity is essential for the induction of tinnitus

“…Given that spontaneous firing of fusiform cells is dependent on their intrinsic ionic conductances (20), we blocked excitatory and inhibitory synaptic transmission to study the role of intrinsic conductances on the observed tinnitus-related DCN hyperactivity. Using whole-cell and cell-attached recordings in DCN slices, we recorded from fusiform cells in control, tinnitus, and nontinnitus mice 1 wk after noise exposure.…”