title: Differential distribution of serotonin receptor subtypes in BNST(ALG) 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-HT(1A) and 5-HT(7) receptors. Type II neurons expressed transcripts for every 5-HT receptor except the 5-HT(2C) receptor. Type II neurons were divided into three sub-populations: Type IIA in which transcripts for 5-HT(3) and 5-HT(7) receptors predominate, Type IIB that mainly express 5-HT(1B) and 5-HT(4) receptor transcripts, and Type IIC in which transcripts for 5-HT(1A) and 5-HT(2A) receptors predominate. Type III neurons were also subdivided into two sub-populations; one that predominantly expressed transcripts for 5-HT(1A), 5-HT(1B) and 5-HT(2A) receptors, and another that mainly expressed transcripts for 5-HT(2C) receptor. Unpredictable shock stress (USS) caused a long-lasting increase in anxiety-like behavior, and a concomitant decrease in 5-HT(1A) transcript expression in Type I-III neurons, as well as an up-regulation of a transcriptional repressor of 5-HT(1A) gene expression, deformed epidermal autoregulatory factor 1 (Deaf-1). Significantly USS decreased 5-HT(1A) protein level, and increased the level of Deaf-1. USS also increased 5-HT(1B) transcript expression in Type III neurons, as well as 5-HT(7) expression in Type I and II neurons. These data suggest that cell type-specific disruption of 5-HT receptor expression in BNST(ALG) neurons may contribute to stress-induced anxiety disorders.
authors.affiliation: Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Atlanta, GA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Hazra
authors.forename: J D
authors.initials: JD
authors.lastname: Guo
authors.forename: J
authors.initials: J
authors.lastname: Dabrowska
authors.forename: D G
authors.initials: DG
authors.lastname: Rainnie
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects; D000818:Animals; D004558:Electric Stimulation / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000145:classification / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011571:Psychoacoustics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D011985:Receptors, Serotonin / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D055139:Sensory Gating / Q000502:physiology; D012686:Septal Nuclei / Q000473:pathology*; D013315:Stress, Psychological / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors
chemical_list: C485478:Deaf1 protein, rat; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D014157:Transcription Factors