Increased Intrinsic Excitability of Lateral Wing Serotonin Neurons of the Dorsal Raphe: A Mechanism for Selective Activation in Stress Circuits

Abstract

The primary center of serotonin (5-HT) projections to the forebrain is the dorsal raphe nucleus (DR), a region known for its role in the limbic stress response. The ventromedial subregion of the DR (vmDR) has the highest density of 5-HT neurons and is the major target in experiments that involve the DR. However, studies have demonstrated that a variety of stressors induce activation of neurons that is highest in the lateral wing subregion (lwDR) and includes activation of lwDR 5-HT neurons. Despite the functional role that the lwDR is known to play in stress circuits, little is known about lwDR 5-HT neuron physiology. Whole cell patch clamp electrophysiology in mice revealed that lwDR 5-HT cells have active and passive intrinsic membrane properties that make them more excitable than vmDR 5-HT neurons. In addition, lwDR 5-HT neurons demonstrated faster in vitro firing rates. Finally, within the vmDR there was a positive correlation between rostral position and increased excitability, among several other membrane parameters. These results are consistent with stressor induced patterns of activation of 5-HT neurons that includes, in addition to lwDR neurons, a small subset of rostral vmDR neurons. Thus increased intrinsic excitability likely forms a major part of the mechanism underlying the propensity to be activated by a stressor. The membrane properties identified in lwDR recordings may thereby contribute to a unique role of lwDR 5-HT neurons in adaptive responses to stress and in the pathobiology of stress-related mood disorders.