Kv1 channels regulate variations in spike patterning and temporal reliability in the avian cochlear nucleus angularis

Diverse physiological phenotypes in a neuronal population can broaden the range of computational capabilities within a brain region. The avian cochlear nucleus angularis (NA) contains a heterogeneous population of neurons whose variation in intrinsic properties results in electrophysiological phenotypes with a range of sensitivities to temporally modulated input. The low-threshold potassium conductance (GKLT) is a key feature of neurons involved in fine temporal structure coding for sound localization but a role for these channels in intensity or spectrotemporal coding has not been established. To determine whether GKLT affects the phenotypical variation and temporal properties of NA neurons, we applied dendrotoxin (DTX), a potent antagonist of Kv1-type potassium channels, to chick brain stem slices in vitro during whole-cell patch clamp recordings. We found a cell-type specific subset of NA neurons were sensitive to DTX: single-spiking NA neurons were most profoundly affected, as well as a subset of tonic firing neurons. Both tonic I (phasic onset bursting) and tonic II (delayed firing) neurons showed DTX sensitivity in their firing rate and phenotypical firing pattern. Tonic III neurons were unaffected. Spike time reliability and fluctuation sensitivity measured in DTX-sensitive NA neurons was also reduced with DTX. Finally, DTX reduced spike threshold adaptation in these neurons, suggesting that GKLT contributes to the temporal properties that allow coding of rapid changes in the inputs to NA neurons. These results suggest that variation in Kv1 channel expression may be a key factor in functional diversity in the avian cochlear nucleus.

Kv1 channels regulate variations in spike patterning and temporal reliability in the avian cochlear nucleus angularis

Diverse physiological phenotypes in a neuronal population can broaden the range of computational capabilities within a brain region. The avian cochlear nucleus angularis (NA) contains a heterogeneous population of neurons whose variation in intrinsic properties results in electrophysiological phenotypes with a range of sensitivities to temporally modulated input. The low-threshold potassium conductance (GKLT) is a key feature of neurons involved in fine temporal structure coding for sound localization but a role for these channels in intensity or spectrotemporal coding has not been established. To determine whether GKLT affects the phenotypical variation and temporal properties of NA neurons, we applied dendrotoxin (DTX), a potent antagonist of Kv1-type potassium channels, to chick brain stem slices in vitro during whole-cell patch clamp recordings. We found a cell-type specific subset of NA neurons were sensitive to DTX: single-spiking NA neurons were most profoundly affected, as well as a subset of tonic firing neurons. Both tonic I (phasic onset bursting) and tonic II (delayed firing) neurons showed DTX sensitivity in their firing rate and phenotypical firing pattern. Tonic III neurons were unaffected. Spike time reliability and fluctuation sensitivity measured in DTX-sensitive NA neurons was also reduced with DTX. Finally, DTX reduced spike threshold adaptation in these neurons, suggesting that GKLT contributes to the temporal properties that allow coding of rapid changes in the inputs to NA neurons. These results suggest that variation in Kv1 channel expression may be a key factor in functional diversity in the avian cochlear nucleus.

Spike threshold adaptation diversifies neuronal operating modes in the auditory brain stem

Single neurons function along a spectrum of neuronal operating modes whose properties determine how the output firing activity is generated from synaptic input. The auditory brain stem contains a diversity of neurons, from pure coincidence detectors to pure integrators and those with intermediate properties. We investigated how intrinsic spike initiation mechanisms regulate neuronal operating mode in the avian cochlear nucleus. Although the neurons in one division of the avian cochlear nucleus, nucleus magnocellularis, have been studied in depth, the spike threshold dynamics of the tonically firing neurons of a second division of cochlear nucleus, nucleus angularis (NA), remained unexplained. The input-output functions of tonically firing NA neurons were interrogated with directly injected in vivo-like current stimuli during whole cell patch-clamp recordings in vitro. Increasing the amplitude of the noise fluctuations in the current stimulus enhanced the firing rates in one subset of tonically firing neurons (“differentiators”) but not another (“integrators”). We found that spike thresholds showed significantly greater adaptation and variability in the differentiator neurons. A leaky integrate-and-fire neuronal model with an adaptive spike initiation process derived from sodium channel dynamics was fit to the firing responses and could recapitulate >80% of the precise temporal firing across a range of fluctuation and mean current levels. Greater threshold adaptation explained the frequency-current curve changes due to a hyperpolarized shift in the effective adaptation voltage range and longer-lasting threshold adaptation in differentiators. The fine-tuning of the intrinsic properties of different NA neurons suggests they may have specialized roles in spectrotemporal processing. NEW & NOTEWORTHY Avian cochlear nucleus angularis (NA) neurons are responsible for encoding sound intensity for sound localization and spectrotemporal processing. An adaptive spike threshold mechanism fine-tunes a subset of repetitive-spiking neurons in NA to confer coincidence detector-like properties. A model based on sodium channel inactivation properties reproduced the activity via a hyperpolarized shift in adaptation conferring fluctuation sensitivity.

Presynaptic GABAergic receptors modulate inhibitory synaptic feedback in the avian cochlear nucleus angularis

Inhibition plays multiple critical roles in the neural processing of sound. In the avian auditory brain stem, the cochlear nuclei receive their principal inhibitory feedback from the superior olivary nucleus (SON) in lieu of local inhibitory circuitry. In the timing pathway, GABAergic inhibitory feedback underlies gain control to enhance sound localization. In the cochlear nucleus angularis (NA), which processes intensity information, how the inhibitory feedback is integrated is not well understood. Using whole cell patch-clamp recordings in chick brain stem slices, we investigated the effects of GABA release on the inhibitory (presumed SON) and excitatory (8th nerve) synaptic inputs onto NA neurons. Pharmacological activation of the metabotropic GABAB receptors with baclofen profoundly suppressed both evoked excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs). Baclofen similarly reduced the frequency of spontaneous IPSCs and EPSCs, but had no significant effect on the current kinetics or amplitudes, indicating a presynaptic locus of modulation. Trains of IPSCs showed substantial transient and sustained short-term synaptic facilitation. Baclofen application reduced the initial IPSC amplitude, but enhanced the relative facilitation over the train via changes in release probability. Comparable levels of GABAB receptor mediated blockade also shifted short-term synaptic plasticity of EPSCs toward less depression. Evoked (but not spontaneous) release of GABA was sufficient to suppress basal release at inhibitory synapses in slices. Overall, the modulation of excitatory and inhibitory inputs of NA neurons via GABAB receptor activation appears to parallel that in the timing pathway.New and NoteworthyAvian cochlear nucleus angularis (NA) neurons are responsible for encoding sound intensity and provide level information for gain control feedback via the superior olivary nucleus. This GABAergic inhibitory feedback was itself modulated in NA via presynaptic, metabotropic GABAB receptor mediated suppression. Excitatory transmission was modulated by the same receptors, suggesting parallel homosynaptic and heterosynaptic mechanisms in both cochlear nuclei.