PMC

Early life experience and social defeat during adulthood interact to alter slc6a4 mRNA expression in adult midbrain serotonergic neurons. A) Mean slc6a4 mRNA expression levels in MS15, AFR, and MS180 rats, regardless of adult experience, based on the mean expression levels in forty-eight subdivisions of the DR. B) Mean slc6a4 mRNA expression levels in adult rats exposed to a novel cage (control condition) or social defeat, regardless of early life experience, based on the mean expression levels in forty-eight subdivisions of the DR. C) Mean slc6a4 mRNA expression levels in MS15, AFR, and MS180 rats exposed to a novel cage control condition (control, left) or social defeat (right) as adults. Slc6a4 mRNA expression was measured 4 h following exposure to a novel cage control condition or to social defeat. **P < 0.01, comparison of MS15 and MS180 groups. ^bP < 0.01, comparison of AFR and MS180 groups. Data are illustrated as means + SEM.

Effects of social defeat on slc6a4 mRNA expression in specific subdivisions of the DR are dependent on early life experience. Graphs illustrate the effects of early life experience and social defeat on slc6a4 mRNA expression in each of the major subdivisions of the DR and the CLi. Data are collapsed across the rostrocaudal extent of each subdivision. A) DRD; B) DRV; C) left DRVL/VLPAG; D) right DRVL/VLPAG; E) DRI; F) CLi; G) combined left and right DRVL/VLPAG. For abbreviations, see legend. *P < 0.05, **P < 0.01, ***P < 0.001, comparison of MS15 and MS180 groups. ^aP < 0.05, ^bP < 0.01, comparison of AFR and MS180 groups. ^§P < 0.05, comparison of control and social defeat groups within the same early life experience treatment group. Data are illustrated as means + SEM.

Social defeat increases slc6a4 mRNA expression in the DRVL/VLPAG region 4 h following exposure to the social defeat paradigm, but only in MS180 rats. Autoradiographic images illustrate slc6a4 mRNA expression at three anatomical levels (rostral, −7.832; mid-rostrocaudal, −8.084; and caudal, −8.336 mm Bregma) from each treatment group including rats exposed to control and social defeat conditions among MS15, AFR, and MS180 rats. In each panel, the DR is at the top and the median raphe nucleus and supralemniscal cell group (B9) are at the bottom. Slc6a4 mRNA expression within the DRVL/VLPAG region is indicated by a line in the social defeat images for MS15, AFR and MS180 at the midrostrocaudal anatomical level. Scale bar, 1 mm.

Early life experience and social defeat during adulthood interact to regulate slc6a4 mRNA expression at specific rostrocaudal levels of subdivisions of the DR. Each graph illustrates the mean slc6a4 mRNA expression levels throughout the rostrocaudal extent of a different subdivision of the DR in MS15 and MS180 rats exposed to a novel cage control condition (control, left) or social defeat (right) as adults. A) DRD; B) DRV; C) left DRVL/VLPAG; D) right DRVL/VLPAG; E) CLi and DRI). For abbreviations, see legend. +P < 0.05, ++P < 0.01, +++P < 0.001, comparison of MS15 and AFR groups. *P < 0.05, **P < 0.01, comparison of MS15 and MS180 groups. ^aP < 0.05, ^bP < 0.01, ^cP < 0.001, comparison of AFR and MS180 groups. ^§P < 0.05, ^§§P < 0.01, comparison of control and social defeat groups within the same early life experience treatment group at the same rostrocaudal level. Data are illustrated as means ± SEM.

Schematic illustration of a midline sagittal section of the rat brainstem showing the subdivisions of the dorsal raphe nucleus (DR) and the caudal linear nucleus (CLi) that were selected for analysis (adapted from ). Red shading indicates regions of the DR and CLi containing slc6a4 mRNA expression. The full sagittal section is shown in the top right corner for reference; the box shows the area illustrated in the main figure. Dashed vertical lines correspond to the rostrocaudal levels selected for analysis, illustrated in . Abbreviations: 3, oculomotor nucleus; CLi, caudal linear nucleus; DRC, dorsal raphe nucleus, caudal part; DRD, dorsal raphe nucleus, dorsal part; DRI, dorsal raphe nucleus, interfascicular part; DRV, dorsal raphe nucleus, ventral part; DTgP, dorsal tegmental nucleus, pericentral part; IPA, interpeduncular nucleus, apical subnucleus; IPC, interpeduncular nucleus, caudal subnucleus; IPR, interpeduncular nucleus, rostral subnucleus; mlf, medial longitudinal fasciculus; MnR, median raphe nucleus; PnR, pontine raphe nucleus; vAq, ventral surface of the cerebral aqueduct, v4V, ventral surface of the 4^th ventricle; xscp, decussation of the superior cerebellar peduncle. Scale bar, 1mm.

Atlas of rat slc6a4 mRNA expression in the midbrain raphe complex (84 μm intervals) used for analysis of subregions of the DR with a high level of neuroanatomical resolution. Photographs are autoradiographic images of slc6a4 mRNA expression as indicated by in situ hybridization histochemistry. The levels chosen for analysis ranged from −7.664 mm Bregma (designated Level 6) though −8.588 mm Bregma (designated Level −5). Abbreviations; CLi, caudal linear nucleus of the raphe; DRD, dorsal raphe nucleus, dorsal part; DRI, dorsal raphe nucleus, interfascicular part; DRV, dorsal raphe nucleus, ventral part; DRVL, dorsal raphe nucleus, ventrolateral part; VLPAG, ventrolateral periaqueductal gray. Scale bar, 1 mm. Adapted from Topographic organization and chemoarchitecture of the dorsal raphe nucleus and the median raphe nucleus. In: Serotonin and Sleep: Molecular, Functional and Clinical Aspects. J.M. Monti, S.R. Pandi-Perumal, B.L. Jacobs, and D.J. Nutt, Eds. Birkhauser Verlag AG, Basel, Switzerland, pp. 25–67. ISBN: 978-3-7643-8560-6, with permission.