Stress Modulation of Opposing Circuits in the Bed Nucleus of the Stria Terminalis

Abstract

The anterior bed nucleus of the stria terminalis (BNST) has been recognized as a critical structure in regulating trait anxiety, contextual fear memory, and appetitive behavior, and is known to be sensitive to stress manipulations. As one of the most complex structures in the central nervous system, the intrinsic circuitry of the BNST is largely unknown; however, recent technological developments have allowed researchers to begin to untangle the internal connections of the nucleus. This research has revealed the possibility of two opposing circuits, one anxiolytic and one anxiogenic, within the BNST, the relative strength of which determines the behavioral outcome. The balance of these pathways is critical in maintaining a normal physiological and behavioral state; however, stress and drugs of abuse can differentially affect the opposing circuitry within the nucleus to shift the balance to a pathological state. In this review, we will examine how stress interacts with the neuromodulators, corticotropin-releasing factor, norepinephrine, dopamine, and serotonin to affect the circuitry of the BNST as well as how synaptic plasticity in the BNST is modulated by stress, resulting in long-lasting changes in the circuit and behavioral state.

High-resolution and cell-type-specific photostimulation mapping shows weak excitatory vs. strong inhibitory inputs in the bed nucleus of the stria terminalis

“…The extent of strong inhibitory connections is consistent with earlier findings showing that GABAergic neurons make up a predominant portion of the general makeup of adBNST and glutamatergic neurons only account for a minority of the overall population (Daniel and Rainnie 2016;Larriva-Sahd 2006;Nguyen et al 2015). Given that BSNT receives strong extrinsic excitatory inputs from the amygdala and other brain regions (Daniel and Rainnie 2016;Kim et al 2013), strong local inhibitory connections can play an important role in modulation of these extrinsic inputs.Because both the detailed neuronal morphology revealed by biocytin staining and input mapped profiles were available, we explored the spatial relationship between dendritic fields and input profiles by examining their overlays, as illustrated in Fig. 4.…”

“…The BNST coordinates neuroendocrine, autonomic and somatomotor responses to anxiety and emotional aspects of stressful events, and it is identified as a key node in neural networks relevant to pathological anxiety and addiction. This area has received increased attention in light of recent physiological and functional studies (Daniel and Rainnie 2016;Deisseroth 2014;Jennings et al 2013;Johansen 2013;Kim et al 2013).…”

“…The BNST coordinates neuroendocrine, autonomic and somatomotor responses to anxiety and emotional aspects of stressful events, and it is identified as a key node in neural networks relevant to pathological anxiety and addiction. This area has received increased attention in light of recent physiological and functional studies (Daniel and Rainnie 2016;Deisseroth 2014;Jennings et al 2013;Johansen 2013;Kim et al 2013).Based on gross anatomical and cytoarchitecture features, the BNST contains a collection of nuclei, and they can be generally divided into anterior and posterior groups by the presence of anterior commissure (Wood and Swann 2005). A number of studies have focused on the anterior dorsal BNST (adBNST) for robust identification and delineation of this region.…”

Impact of Stress on the Brain: Pathology, Treatment and Prevention

“…Rainnie and colleagues provide a thorough review of the electrophysiological underpinnings of the BNST-dependent stress response (Daniel and Rainnie, 2016). This chapter is followed by a review of new findings of BNST function in humans, in particularly how the human BNST modulates anxiety and stress responses using fMRI approaches (Avery et al, 2016).…”

Relaxin-3/RXFP3 signalling in mouse hypothalamus: no effect of RXFP3 activation on corticosterone, despite reduced presynaptic excitatory input onto paraventricular CRH neurons in vitro

“…The BNST is an anatomically complex structure with multiple subdivisions ) and is a node for stress information integration (Lebow and Chen 2016). Initial anatomical studies revealed RXFP3 expression in multiple subdivisions of mouse BNST (Smith et al 2010), but a detailed analysis of RXFP3 expression patterns in the BNST would be required to determine the possible role of these receptors in HPA axis regulation, as activation or inhibition of individual subdivisions of the BNST can have opposing effects (see Biag et al 2012;Daniel and Rainnie 2016). Furthermore, high-frequency stimulation of the BNST produced a reduction in subsequently evoked field potentials in PVN, and this reduction was blocked by an NMDA receptor antagonist, suggesting that PVNprojecting glutamatergic neurons can mediate neuroplasticity within the PVN (Tartar et al 2006).…”