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

J Neurophysiol. 2010 May;103(5):2652-63. doi: 10.1152/jn.01132.2009. Epub 2010 Mar 17.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials
  • Animals
  • Cell Membrane / drug effects
  • Cell Membrane / physiology
  • Electric Impedance
  • Immunohistochemistry
  • In Vitro Techniques
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Male
  • Membrane Potentials / physiology
  • Mice
  • Mice, Transgenic
  • Neurons / drug effects
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Raphe Nuclei / drug effects
  • Raphe Nuclei / physiology*
  • Serotonin / metabolism*
  • Stress, Psychological / physiopathology
  • Time Factors

Substances

  • Luminescent Proteins
  • Serotonin