Regulation of forebrain GABAergic stress circuits following lesion of the ventral subiculum.
Ventral subiculum (vSUB) lesions enhance corticosterone responses to psychogenic stressors via trans-synaptic influences on paraventricular nucleus (PVN) neurons. Synaptic relays likely occur in GABA-rich regions interconnecting the vSUB and PVN. The current study examines whether vSUB lesions compromise stress-induced c-fos induction and GABA biosynthetic capacity in putative limbic-hypothalamic stress relays. Male Sprague-Dawley rats received bilateral ibotenate or sham lesions of the vSUB. Animals were divided into two groups, with one group receiving exposure to novelty stress and the other left unstressed. Exposure to novelty stress increased c-fos mRNA expression in the PVN to a greater degree in vSUB lesion relative to shams, consistent with an inhibitory role for the vSUB in the HPA stress response. However, c-fos induction was not affected in other forebrain GABAergic stress pathways, such as the lateral septum, medial preoptic area or dorsomedial hypothalamus. vSUB lesions increased GAD65 or GAD67 mRNA levels in several efferent targets, including anterior and posterior subnuclei of the bed nucleus of the stria terminalis and lateral septum. Lesions did not effect stress-induced increases in GAD65 expression in principal output nuclei of the amygdala. The current data suggest that loss of vSUB innervations produces a compensatory increase in GAD expression in subcortical targets; however, this up-regulation is insufficient to block lesion-induced stress hyperresponsiveness, perhaps driven by amygdalar disinhibition of the PVN.
Mueller
Nancy K
NK
Department of Psychiatry, University of Cincinnati, 2170 E. Galbraith Road, Cincinnati, OH 45237-0506, USA.
Dolgas
C Mark
CM
Herman
James P
JP
D000818:Animals; D001345:Autoradiography; D005968:Glutamate Decarboxylase / Q000096:biosynthesis / Q000235:genetics; D006624:Hippocampus / Q000293:injuries* / Q000473:pathology; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D016548:Prosencephalon / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D018075:RNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D007527:Isoenzymes; D016760:Proto-Oncogene Proteins c-fos; D018075:RNA, Complementary; D012333:RNA, Messenger; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2