Exciting Inhibition

Abstract

Some neurons exhibit high levels of spontaneous activity, allowing synaptic input to "tune" the system either up or down, that is, to increase or decrease the activity of these spontaneously firing neurons (see Häusser and Monsivais). Nelson et al. examined the plasticity of the spontaneously active neurons of the medial vestibular nucleus (MVN), which is responsible for the vestibulo-ocular reflex that stabilizes images on the retina during head movement by altering the rate of eye movements. In MVN slices, transient activation of inhibitory synaptic input leads to prolonged increase in spontaneous firing rate and in the "gain" of the firing response (slope of the relationship between the input current and the firing rate) once inhibitory input is terminated, a response termed firing rate potentiation (FRP). FRP was also produced in response to application of the inhibitory transmitters γ-aminobutyric acid and glycine, and in response to direct hyperpolarization by current injection. Synaptic inhibition produced a decrease in afterhyperpolarization (AHP), a change in membrane potential mediated by potassium currents; thus, it implicated potassium channels as participating in FRP. Stimuli that produced FRP also decreased intracellular calcium concentration, and transient depletion of calcium by application of a calcium chelator or by transient removal from the extracellular medium also triggered FRP. Inhibition of calcium-activated potassium channels could account for the change in AHP and contribute to the induction of FRP. Pharmacological inhibition of either the SK or BK channels stimulated FRP; however, only when BK channels were inhibited was hyperpolarization of the neurons unable to trigger further FRP. Thus, decreased calcium leading to inhibition of BK channels appears to be central to the inhibition-mediated stimulation of spontaneous activity. A. B. Nelson, C. M. Krispel, C. Sekirnjak, S. du Lac, Long-lasting increases in intrinsic excitability triggered by inhibition. Neuron 40 , 609-620 (2003). [Online Journal] M. Häusser, P. Monsivais, Less means more: Inhibition of spontaneous firing triggers persistent increases in excitability. Neuron 40 , 449-450 (2003). [Online Journal]