Ventral subicular interaction with the hypothalamic paraventricular nucleus: Evidence for a relay in the bed nucleus of the stria terminalis

Abstract

The axonal projections of the ventral subiculum to the bed nucleus of the stria terminalis (BST) were examined in the rat with the anterograde neuronal tracer Phaseolus vulgaris-leucoagglutinin (PHA-L). Axons originating in the ventral subiculum coursed to the BST through either the fimbria-fornix, or a pathway involving the stria terminalis via the amygdala. Ventral subicular axons gave rise to dense terminal networks that were preferentially distributed in medial and ventral subregions of the BST. The distribution of subicular fibers and terminals was examined in relation to BST neurons that project to the hypothalamic paraventricular nucleus (PVN). In these cases, discrete iontophoretic injections of the retrograde tracer Fluoro-gold were made in the PVN, with PHA-L delivered to the ipsilateral ventral subiculum. An immunocytochemical double-labeling protocol was then employed for the simultaneous detection of PHA-L and Fluoro-gold, and provided light microscopic evidence for subicular input to PVN-projecting cells located within the BST. In a second series of experiments, the gamma-amino butyric acid (GABA)ergic nature of the BST was examined by in situ hybridization histochemistry for detection of transcripts encoding GAD67 mRNA. The studies revealed that a high proportion of BST neurons express GAD67 transcripts. Also, experiments combining Fluoro-gold tracing with GAD67 in situ hybridization suggested that a proportion of PVN-projecting neurons in the BST are GABAergic. Taken together, the results of these sets of studies suggest that the inhibitory influences of the hippocampus on the PVN might be relayed through specific portions of the BST. These findings may have important implications for our understanding of the neural regulation of the hypothalamic-pituitary-adrenal axis.

The role of the posterior medial bed nucleus of the stria terminalis in modulating hypothalamic–pituitary–adrenocortical axis responsiveness to acute and chronic stress

“…The posterior medial BST receives input from numerous HPA axis-regulating limbic structures including the ventral subiculum, medial prefrontal cortex, and medial nucleus of the amygdala (Cullinan et al, 1993;Dong et al, 2001a;Dong and Swanson, 2004;Gu et al, 2003). The BSTpm is positioned to integrate emotional information from the basolateral amygdala and/or central nucleus of the amygdala into the stress response via the anterior lateral BST nuclei, which is known to regulate fear and anxiety-like behavior (see (Walker et al, 2003)).…”

“…The excitatory effects of posterior medial BST lesions on HPA axis responses to acute stress are similar to those seen following lesions of the ventral subiculum (Herman et al, 1998) and medial prefrontal cortex (Figueiredo et al, 2003), raising the possibility that the BST may relay information from these structures to the PVN. In the case of the ventral subiculum, anatomical interconnections with the PVN via this portion of the BST have been previously established (Cullinan et al, 1993). However, it is important to note that the role of cortical and hippocampal regions in chronic stress regulation have yet to be established, thus it is unclear whether a partial role of the BST on HPA axis facilitation is mediated by these structures.…”

“…Anatomical studies indicate that the hippocampus and amygdala mainly relay signals by heavily innervating PVN-projecting basal forebrain and hypothalamic structures. Notably, the bed nucleus of the stria terminalis (BST) is among the main extrahypothalamic regions that receives abundant input from all of the noted limbic regions (Cullinan et al, 1993;Dong et al, 2001b;Dong and Swanson, 2004;Gu et al, 2003;Sawchenko and Swanson, 1983).…”

Resolving the neural circuits of anxiety

“…Initiation of fear and sustained anxiety responses requires the recruitment of the BNST 7 , which occurs partly as a result of direct innervation by BLA afferents, as well as through dense glutamatergic input from the HPC 81,82 , the mPFC, the entorhinal cortex, and insular cortex 55,83 .…”

Repeated Stimulation of CRF Receptors in the BNST of Rats Selectively Induces Social but not Panic-Like Anxiety

“…The bed nucleus of the stria terminalis (BNST) is thought to be a key structure for mediating anxiety-like responses elicited by unconditioned or ethologically valid threats (Lee and Davis, 1997;Walker and Davis, 1997;Davis and Shi, 1999;Fendt et al, 2003), and is a key structure that relays and integrates limbic and autonomic information related to stress responses (Cullinan et al, 1993;Forray and Gysling, 2004;Herman et al, 2004). The BNST has also been identified as an area critical for stress-induced reinstatement of drug-seeking behaviors, and for the increased anxiety associated with protracted withdrawal (Erb and Stewart, 1999;Leri et al, 2002;Aston-Jones and Harris, 2004).…”