Activation of the neural pathway from the dorsolateral bed nucleus of the stria terminalis to the central amygdala induces anxiety‐like behaviors

Abstract

The bed nucleus of the stria terminalis (BNST) and the central amygdala (CeA) comprise a forebrain unit that has been described as the “extended amygdala”. These two nuclei send dense projections to each other and have been implicated in the regulation of negative emotional states, including anxiety and fear. The present study employed an optogenetic technique to examine whether stimulation of CeA‐projecting dorsolateral BNST (dlBNST) neuron terminals would influence anxiety‐like behaviors in male Sprague‐Dawley rats. Photostimulation of CeA‐projecting dlBNST neuron terminals produced anxiogenic effects in an elevated plus maze test. This finding is inconsistent with previous reports showing that optogenetic stimulation of BNST neurons projecting to the lateral hypothalamus (LH) and ventral tegmental area (VTA) produces anxiolytic rather than anxiogenic effects. To address this issue, electrophysiological analyses were conducted to characterize dlBNST neurons projecting to the CeA, LH, and VTA. dlBNST neurons can be electrophysiologically classified into three distinct cell types (types I–III) according to their responses to depolarizing and hyperpolarizing current injections. Whole‐cell patch‐clamp recordings revealed that more than 60% of the CeA‐projecting dlBNST neurons were type II, whereas approximately 80% of the LH‐ and VTA‐projecting dlBNST neurons were type III. These electrophysiological results will help elucidate the mechanisms underlying the heterogeneity of BNST neurons during the regulation of anxiety‐like behaviors.

Whole-Brain Map of Long-Range Monosynaptic Inputs to Different Cell Types in the Amygdala of the Mouse

“…The CeA is an important region of the amygdala, orchestrating a diverse set of behaviors, including fear, anxiety, and defensive responses [ 2 , 42 , 43 ]. Our rabies virus input-tracing identified several principal input regions reported in previous studies, such as the PVT [ 44 ], AI [ 45 ], BST [ 46 ], and substantia nigra pars compacta [ 47 ] (Figs 4 and 5 , Table S1). Projections from the lateral parabrachial nucleus to the CeA may be essential for sodium intake [ 48 – 50 ].…”

Behavioral and brain mechanisms mediating conditioned flight behavior in rats

“…Based on this, we speculate that concurrent CeA and BNST input to the PAG could drive the threshold-like mechanism underlying context-dependent flight behavior (Nagy and Paré, 2008). Alternatively, BNST projections to the CeA may represent necessary inputs to drive CeA CRH+ neurons to gate flight behavior (Fadok et al, 2017; Gungor et al, 2015; Gungor and Paré, 2016; Yamauchi et al, 2018). Future work should investigate these pathways and their potential role in mediating flight behavior in the SCS paradigm.…”

Tonic Suppression of the Mesolimbic Dopaminergic System by Enhanced Corticotropin-Releasing Factor Signaling Within the Bed Nucleus of the Stria Terminalis in Chronic Pain Model Rats

“…Current-clamp recordings were conducted to characterize dlBNST neurons. Hyperpolarization-activated cation current (I h ) was identified as described previously (Yamauchi et al, 2018). Specifically, the occurrence of I h was verified by the presence of a "voltage-sag" equal to or Ͼ10% of the total voltage deflection upon the hyperpolarizing current injection, which elicited a membrane voltage of ϳϪ100 mV.…”

“…We previously reported that ϳ80% of the VTA-projecting dlBNST neurons are type III (Yamauchi et al, 2018). Thus, sIPSCs were recorded from the VTA-projecting dlBNST type III neurons 2 and 4 weeks after the SNL or sham surgery (Fig.…”