The dorsal raphe nucleus (DR) has a topographic neuroanatomy consistent with the idea that different parts of this nucleus subserve different functions. Here we use dual in situ hybridization to describe the rostral-caudal neurochemical distribution of three major cell groups, serotonin (5-hydroxytryptamine; 5-HT), γ-aminobutyric acid (GABA), and catecholamine, and their relative colocalization with each other and mRNA encoding four different receptor subtypes that have been described to influence DR responses, namely, 5HT-1A, α 1b adrenergic (α 1b ADR), and corticotropinreleasing factor type 1 (CRF-R1) and 2 (CRF-R2) receptors. Serotonergic and GABAergic neurons were distributed throughout the rostral-caudal extent of the DR, whereas catecholaminergic neurons were generally restricted to the rostral half of the nucleus. These phenotypes essentially represent distinct cell populations, because the neurochemical markers were rarely colocalized. Both 5HT-1A and α 1b ADR mRNA were highly expressed throughout the DR, and the vast majority of serotonergic neurons expressed both receptors. A smaller percentage of GABAergic neurons also expressed 5HT-1A or α 1b ADR mRNA. Very few catecholaminergic cells expressed either 5HT-1A or α 1b ADR mRNA. CRF-R1 mRNA was detected only at very low levels within the DR, and quantitative colocalization studies were not technically feasible. CRF-R2 mRNA was mainly expressed at the middle and caudal levels of the DR. At midlevels, CRF-R2 mRNA was expressed exclusively in serotonin neurons, whereas, at caudal levels, approximately half the CRF-R2 mRNA was expressed in GABAergic neurons. The differential distribution of distinct neurochemical phenotypes lends support to the idea of functional differentiation of the DR.
Indexing termsGABA; tyrosine hydroxylase; serotonin; corticotropin; dual in situ hybridizationThe dorsal raphe nucleus (DR) contains the highest concentration of serotonin neurons in the brain and has extensive ascending projections that innervate most forebrain structures (Steinbusch, 1981). These projection neurons have been shown to regulate a wide variety of physiological responses and behaviors, including sleep-wake states, feeding, nociception, *Correspondence to: Heidi E.W. Day, Department of Psychology and Center for Neuroscience, University of Colorado, Muenzinger Building, Rm. D244, Boulder, CO 80309-0345. E-mail: heididay@psych.colorado.edu. (Jacobs and Azmitia, 1992). In addition, increasing evidence has implicated serotonin in affective conditions, such as depression and anxiety (Kahn et al., 1988;Graeff et al., 1996).
NIH Public AccessHowever, the DR is not a homogeneous structure, and serotonin neurons have been classified into subpopulations according to their electrophysiological properties in behaving animals. For example, the activity of type I neurons that make up the majority of serotonergic neurons is correlated with the degree of behavioral arousal and motor activity (Jacobs and Fornal, 1999). In contrast, the firing rate of the small group...