Differential distribution of serotonin receptor subtypes in BNSTALG neurons: Modulation by unpredictable shock stress

Abstract

The bed nucleus of the stria terminalis (BNST) plays a critical role in regulating the behavioral response to stress. Stressors that activate the BNST also activate serotonergic (5-HT) systems. Hence, maladaptive changes of 5-HT receptor expression may contribute to stress-induced anxiety disorders. The BNST contains three neuronal types, Type I–III neurons. However, little is known about 5-HT receptor subtypes mRNA expression in these neurons, or whether it can be modulated by stress.Whole-cell patch clamp recording from Type I–III neurons was used in conjunction with single cell reverse transcriptase polymerase chain reaction (RT-PCR) to characterize 5-HT receptor mRNA expression, and examine the effects of stress on this expression. We report that Type I neurons expressed mRNA transcripts predominantly for 5-HT1A and 5-HT7 receptors. Type II neurons expressed transcripts for every 5-HT receptor except the 5-HT2C receptor. Type II neurons were divided into three sub-populations: Type IIA in which transcripts for 5-HT3 and 5-HT7 receptors predominate, Type IIB that mainly express 5-HT1B and 5-HT4 receptor transcripts, and Type IIC in which transcripts for 5-HT1A and 5-HT2A receptors predominate. Type III neurons were also subdivided into two sub-populations; one that predominantly expressed transcripts for 5-HT1A, 5-HT1B and 5-HT2A receptors, and another that mainly expressed transcripts for 5-HT2C receptor.Unpredictable shock stress (USS) caused a long-lasting increase in anxiety-like behavior, and a concomitant decrease in 5-HT1A transcript expression in Type I–III neurons, as well as an up-regulation of a transcriptional repressor of 5-HT1A gene expression, deformed epidermal autoregulatory factor 1 (Deaf-1). Significantly USS decreased 5-HT1A protein level, and increased the level of Deaf-1. USS also increased 5-HT1B transcript expression in Type III neurons, as well as 5-HT7 expression in Type I and II neurons. These data suggest that cell type-specific disruption of 5-HT receptor expression in BNSTALG neurons may contribute to stress-induced anxiety disorders.