Increased Intrinsic Excitability of Lwdr 5-ht Neurons 1

24 The primary center of serotonin (5-HT) projections to the forebrain is the 25 dorsal raphe nucleus (DR), a region known for its role in the limbic stress 26 response. The ventromedial subregion of the DR (vmDR) has the highest density 27 of 5-HT neurons and is the major target in experiments that involve the DR. 28 However, studies have demonstrated that a variety of stressors induce activation 29 of neurons that is highest in the lateral wing subregion (lwDR) and includes 30 activation of lwDR 5-HT neurons. Despite the functional role that the lwDR is 31 known to play in stress circuits, little is known about lwDR 5-HT neuron 32 physiology. Whole-cell patch clamp electrophysiology in mice revealed that 33 lwDR 5-HT cells have active and passive intrinsic membrane properties that 34 make them more excitable than vmDR 5-HT neurons. In addition, lwDR 5-HT 35 neurons demonstrated faster in vitro firing rates. Finally, within the vmDR there 36 was a positive correlation between rostral position and increased excitability, 37 among several other membrane parameters. These results are consistent with 38 stressor induced patterns of activation of 5-HT neurons that includes, in addition 39 to lwDR neurons, a small subset of rostral vmDR neurons. Thus, increased 40 intrinsic excitability likely forms a major part of the mechanism underlying the 41 propensity to be activated by a stressor. The membrane properties identified in 42 lwDR recordings may thereby contribute to a unique role of lwDR 5-HT neurons 43 Increased intrinsic excitability of lwDR 5-HT neurons 4 in adaptive responses to stress and in the pathobiology of stress-related mood 44 disorders. 45 46 47