Regulation of Firing Response Gain by Calcium-Dependent Mechanisms in Vestibular Nucleus Neurons

Abstract

Smith, Marianne R., Alexandra B. Nelson, and Sascha du Lac. Regulation of firing response gain by calcium-dependent mechanisms in vestibular nucleus neurons. J Neurophysiol 87: 2031-2042, 2002; 10.1152/jn.00821.2001. Behavioral reflexes can be modified by experience via mechanisms that are largely unknown. Within the circuitry for the vestibuloocular reflex (VOR), neurons in the medial vestibular nucleus (MVN) show adaptive changes in firing rate responses that are correlated with VOR gain (the ratio of evoked eye velocity to input head velocity). Although changes in synaptic strength are typically assumed to underlie gain changes in the VOR, modulation of intrinsic ion channels that dictate firing could also play a role. Little is known, however, about how ion channel function or regulation contributes to firing responses in MVN neurons. This study examined contributions of calcium-dependent currents to firing responses in MVN neurons recorded with whole cell patch electrodes in rodent brain stem slices. Firing responses were remarkably linear over a wide range of firing rates and showed modest spike frequency adaptation. Firing response gain, the ratio of evoked firing rate to input current, was reduced by increasing extracellular calcium and increased either by lowering extracellular calcium or with antagonists to SK-and BK-type calcium-dependent potassium channels and Nand T-type calcium channels. Blockade of SK channels occluded gain increases via N-type calcium channels, while blocking BK channels occluded gain increases via presumed T-type calcium channels, indicating specific coupling of potassium channels and their calcium sources. Selective inhibition of Ca 2ϩ /calmodulin-dependent kinase II and broad-spectrum inhibition of phosphatases modulated gain via BK-dependent pathways, indicating that firing responses are tightly regulated. Modulation of firing response gain by phosphorylation provides an attractive mechanism for adaptive control of VOR gain. I N T R O D U C T I O NBehavioral responses to sensory stimuli are governed by mechanisms operating at the level of circuits, synapses, and intrinsic membrane properties, all of which contribute to neuronal excitability in sensory-motor pathways. Although experience-dependent changes in behavior are commonly thought to arise from changes in synaptic strength, a growing body of evidence indicates that ion channels controlling firing responses can be strongly influenced by neuronal activity (Aizenman and Linden 2000; Desai et al. 1999;Ganguly et al. 2000;Turrigiano et al. 1994). These findings raise the possibility that regulation of ion channels could contribute to modulation of behavioral responses.The vestibuloocular reflex (VOR) provides a particularly tractable system for investigating the roles of intrinsic currents in behavioral signaling and plasticity. The function of the VOR is to stabilize images on the retina during self-motion by producing eye movements that compensate for motion of the head. This simple behavioral reflex is remarkably adaptab...

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