Ionic mechanism of long-lasting discharges of action potentials triggered by membrane hyperpolarization in the medial lateral habenula.

摘要

The activation of inhibitory synapses typically suppresses the generation of action potentials by hyperpolarizing the membrane of postsynaptic cells. In contrast to such conventional action of inhibitory synapses, we report here the ionic mechanism through which hyperpolarizing synapses trigger long-lasting discharges of action potentials that persist up to several tens of seconds. By using extracellular and intracellular recordings in slice preparations, we demonstrate that the activation of synaptic input from the limbic forebrain generates transient hyperpolarizing postsynaptic potentials in neurons of the medial part of the lateral habenular nucleus of the epithalamus. The synaptic hyperpolarization then sets off the coordinated activation of a distinct set of membrane ion channels and intracellular Ca2+ mobilization by internal stores. The activation of these cellular events in distinct temporal order drives a persistent depolarization of habenular cells and promotes long-lasting discharges of tonic action potentials. The cells in the medial division of the lateral habenula project to dopamine and serotonin cells in the midbrain. We suggest that these habenular cells, by generating persistent action potentials in response to a transient increase in the activity of the limbic forebrain, may contribute to the regulation of the serotonergic and dopaminergic activity in the brain.