Contribution of the Ventral Subiculum to Inhibitory Regulation of the Hypothalamo‐Pituitary‐Adrenocortical Axis

Abstract

Anatomical studies indicate that the ventral subiculum is in a prime position to mediate hippocampal inhibition of the hypothalamo-pituitary-adrenocortical (HPA) axis. The present study evaluated this hypothesis by assessing HPA function following ibotenic acid lesion of the ventral subiculum region. Rats with lesions of the ventral subiculum (vSUB) or ventral hippocampus (vHIPPO) did not show changes in basal corticosterone (CORT) secretion at either circadian peak or nadir time points when compared to sham-lesion rats (SHAM) or unoperated controls. However, rats with vSUB lesions exhibited a prolonged glucocorticoid stress response relative to all other groups. Baseline CRH mRNA levels were significantly increased in the medial parvocellular paraventricular nucleus (PVN) of the vSUB group relative to controls. CRH mRNA differences were particularly pronounced at caudal levels of the nucleus, suggesting topographic organization of vSUB interactions with PVN neurons. Notably, the vHIPPO group, which received large lesions of ventral CA1, CA3 and dentate gyrus without significant subicular damage, showed no change in stress-induced CORT secretion, suggesting that the ventral subiculum proper is principally responsible for ventral hippocampal actions on the HPA stress response. No differences in medial parvocellular PVN AVP mRNA expression were seen in either the vSUB or vHIPPO groups. The results indicate a specific inhibitory action of the ventral subiculum on HPA activation. The increase in CRH biosynthesis and stress-induced CORT secretion in the absence of changes in baseline CORT secretion or AVP mRNA expression suggests that the inhibitory actions of ventral subicular neurons affect the response capacity of the HPA axis.

Selective Hippocampal Lesions Do Not Increase Adrenocortical Activity

“…Several studies have shown that damage to the hippocampus increases basal glucocorticoid secretion (Fendler et al, 1961;Kim and Kim, 1961;Knigge, 1961;Moberg et al, 1971;Fischette et al, 1980;Wilson et al, 1980;Sapolsky et al, 1984Sapolsky et al, , 1991Herman et al, 1989), but these lesions were made either by aspiration or by transection of the fimbria-fornix and caused damage to bypassing fibers as well as adjacent brain systems, including the parahippocampal cortices and several subcortical structures. Other studies failed to identify a hippocampal inhibitory influence on the HPA axis (Coover et al, 1971;Lanier et al, 1975;Conforti and Feldman, 1976;Smotherman et al, 1981;Bradbury et al, 1993;Herman et al, 1995) but there was only incomplete damage to the hippocampus in these studies. The remaining tissue may have been sufficient to maintain hippocampal feedback inhibition of the HPA axis.…”

Neuroendocrine Responses to a Cold Pressor Stimulus in Polydipsic Hyponatremic and in Matched Schizophrenic Patients

“…Thus this segment of the hippocampus normally constrains AVP and ACTH responses to psychological stress (Herman et al, 1995(Herman et al, , 2005Mueller et al, 2004;Nettles et al, 2000); the findings in patients are recreated in an animal model of schizophrenia, which disrupts the neurodevelopment of this brain region (Mitchell and Goldman, 2004); and this subset of patients exhibits diminished anterior hippocampal volume (Goldman et al, 2005) as well as other impairments indicative of hippocampal-mediated neuroendocrine dysfunction (Goldman et al, 2006). Finally, our unpublished data demonstrate a significant association between anterior hippocampal volume and the cold pressor AVP response in hyponatremic polydipsic patients (r ¼ À0.825, p ¼ 0.022).…”

“…In this regard, hippocampal function varies along its longitudinal axis in both rodents (Bannerman et al, 2004;Moser and Moser, 1998;Risold and Swanson, 1996) and primates (Barbas and Blatt, 1995;Strange et al, 1999;Strange and Dolan, 2001), and structural findings are often more prominent in one or the other end of the hippocampus in patients (Narr et al, 2004;Pegues et al, 2003;Szeszko et al, 2003;Velakoulis et al, 2001;Weiss et al, 2005). The ventral segment in rodents (analogous to anterior segment in primates (Rubin et al, 1966)) modifies neuroendocrine (Herman et al, 1995(Herman et al, , 2005Mueller et al, 2004;Nettles et al, 2000) and behavioral (Flores et al, 2005;Trivedi and Coover, 2004) responses to psychological but not physical stresses (but see Tuvnes et al, 2003). Indeed, an animal model of schizophrenia, in which the development of this segment is disrupted in the neonatal rat (Lipska, 2004), exhibits increased AVP and HPA axis responses to a psychological stimulus (Chrapusta et al, 2003;Mitchell and Goldman, 2004) as well as enhanced behavioral (Flores et al, 2005) responses to psychological stress.…”

Social Stress in Hamsters: Defeat Activates Specific Neurocircuits within the Brain

“…Surprisingly, two brain regions shown to play a role in stress responsivity were not activated in SUB males in the present study. The hippocampus (CA1-3 and subiculum) has been implicated in the mechanism of glucocorticoid negative feedback (for review, see Jacobson and Sapolsky, 1991;Herman et al, 1995). The DM H has been implicated in mediating cardiovascular responses to stress (De Novellis et al, 1995;Stotz-Potter et al, 1996b), as well as a possible role in stress-induced release of ACTH (Stotz-Potter et al, 1996a).…”