Day Heidi E W, Greenwood Benjamin N, Hammack Sayamwong E, Watkins Linda R, Fleshner Monika, Maier Steven F, Campeau Serge
Department of Psychology and Center for Neuroscience, University of Colorado, Boulder, Colorado 80309, USA.
J Comp Neurol. 2004 Jun 28;474(3):364-78. doi: 10.1002/cne.20138.
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), gamma-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, alpha(1b) adrenergic (alpha(1b) ADR), and corticotropin-releasing 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 alpha(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 alpha(1b) ADR mRNA. Very few catecholaminergic cells expressed either 5HT-1A or alpha(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.
中缝背核(DR)具有一种拓扑神经解剖结构,这与该核的不同部分发挥不同功能的观点相一致。在此,我们运用双重原位杂交技术来描述三种主要细胞群(血清素,即5-羟色胺;5-HT、γ-氨基丁酸;GABA和儿茶酚胺)的头-尾神经化学分布,以及它们彼此之间的相对共定位情况,还有与编码四种不同受体亚型的mRNA的共定位情况,这四种受体亚型已被描述为可影响中缝背核的反应,即5HT-1A、α(1b)肾上腺素能(α(1b) ADR)、促肾上腺皮质激素释放因子1型(CRF-R1)和2型(CRF-R2)受体。血清素能和GABA能神经元分布于中缝背核从头至尾的范围,而儿茶酚胺能神经元通常局限于该核的前半部分。这些表型本质上代表了不同的细胞群体,因为神经化学标记很少共定位。5HT-1A和α(1b) ADR mRNA在整个中缝背核中均高度表达,并且绝大多数血清素能神经元表达这两种受体。较小比例的GABA能神经元也表达5HT-1A或α(1b) ADR mRNA。很少有儿茶酚胺能细胞表达5HT-1A或α(1b) ADR mRNA。CRF-R1 mRNA仅在中缝背核内以非常低的水平被检测到,并且定量共定位研究在技术上不可行。CRF-R2 mRNA主要表达于中缝背核的中部和尾部水平。在中部水平,CRF-R2 mRNA仅在血清素神经元中表达,而在尾部水平,大约一半的CRF-R2 mRNA在GABA能神经元中表达。不同神经化学表型的差异分布支持了中缝背核功能分化的观点。