scholarly journals A prefrontal-bed nucleus of the stria terminalis circuit limits fear to uncertain threat

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Lucas R Glover ◽  
Kerry M McFadden ◽  
Max Bjorni ◽  
Sawyer R Smith ◽  
Natalie G Rovero ◽  
...  
Keyword(s):  
Neural Correlates ◽  
Stria Terminalis ◽  
Infralimbic Cortex ◽  
Neural Basis ◽  
Bed Nucleus ◽  
Aversive Events ◽  
Equivalent Number ◽  
Partial Association ◽  
History Of

In many cases of trauma, the same environmental stimuli that become associated with aversive events are experienced on other occasions without adverse consequence. We examined neural circuits underlying partially reinforced fear (PRF), whereby mice received tone-shock pairings on half of conditioning trials. Tone-elicited freezing was lower after PRF conditioning than fully reinforced fear (FRF) conditioning, despite an equivalent number of tone-shock pairings. PRF preferentially activated medial prefrontal cortex (mPFC) and bed nucleus of the stria terminalis (BNST). Chemogenetic inhibition of BNST-projecting mPFC neurons increased PRF, not FRF, freezing. Multiplexing chemogenetics with in vivo neuronal recordings showed elevated infralimbic cortex (IL) neuronal activity during CS-onset and freezing-cessation; these neural correlates were abolished by chemogenetic mPFC®BNST inhibition. These data suggest mPFC®BNST neurons limit fear to threats with a history of partial association with an aversive stimulus, with potential implications for understanding the neural basis of trauma-related disorders.

scholarly journals Solitary Nitric Oxide Signaling Mediates Mild Stress-Induced Anxiety and Norepinephrine Release in the Bed Nucleus of the Stria Terminalis during Protracted Ethanol Withdrawal

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Zhenglin Zhao ◽  
Sang Chan Kim ◽  
Yu Jiao ◽  
Yefu Wang ◽  
Bong Hyo Lee ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Elevated Plus Maze ◽  
In Vivo Microdialysis ◽  
Ethanol Withdrawal ◽  
Mild Stress ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Nitric Oxide Signaling ◽  
Plus Maze

Ethanol withdrawal (EtOHW) alters the pattern of neurohormonal and behavioral response toward internal and external stimuli, which mediates relapse to alcohol use even after a long period of abstinence. Increased noradrenergic signaling from the nucleus tractus solitarius (NTS) to the bed nucleus of the stria terminalis (BNST) during EtOHW underlies withdrawal-induced anxiety, while nitric oxide synthase (NOS) inhibitors injected into the periaqueductal area attenuate EtOHW-induced anxiety. Therefore, this study investigated the involvement of NOS within the NTS in anxiety and increased norepinephrine (NE) release in the BNST during protracted EtOHW in rats exposed to a mild stress. Rats were intraperitoneally administered 3 g/kg/day EtOH for 21 days followed by 28 days of withdrawal, and on the 28th day of withdrawal, the rats were subjected to restraint stress for 7 minutes. The elevated plus maze test was employed to evaluate anxiety-like behavior in rats, and in vivo microdialysis was used to measure the extracellular NE level in the BNST. In elevated plus maze tests, EtOHW rats but not EtOH-naive rats exhibited anxiety-like behavior when challenged with 7-minute mild restraint stress, which was, respectively, mitigated by prior intra-NTS infusion of the nitric oxide scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), nonselective NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME), or selective neuronal NOS (nNOS) inhibitor 7-nitroindazole (7-NI). Each of these agents also decreased the plasma corticosterone levels in EtOHW rats. In in vivo microdialysis, prior intra-NTS infusion of carboxy-PTIO, L-NAME, or 7-NI attenuated the mild stress-induced NE release in the BNST of EtOHW rats. Additionally, EtOHW rats showed increased solitary nNOS gene and protein expression. Moreover, the anxiolytic effect of intra-NTS administration of 7-NI was abolished by subsequent intra-NTS administration of sodium nitroprusside. These results suggest that elevation of solitary nitric oxide signaling derived from nNOS mediates stress-precipitated anxiety and norepinephrine release in the BNST during protracted EtOHW.

scholarly journals In vivo voltammetry monitoring of electrically evoked extracellular norepinephrine in subregions of the bed nucleus of the stria terminalis

2012 ◽  
Vol 107 (6) ◽  
pp. 1731-1737 ◽  
Author(s):  
Natalie R. Herr ◽  
Jinwoo Park ◽  
Zoé A. McElligott ◽  
Anna M. Belle ◽  
Regina M. Carelli ◽  
...  
Keyword(s):  
Carbon Fiber ◽  
Mode Of Delivery ◽  
Simultaneous Detection ◽  
Local Application ◽  
Stria Terminalis ◽  
Pharmacological Agents ◽  
Bed Nucleus ◽  
Carbon Fiber Microelectrode ◽  
Systemic Application

Norepinephrine (NE) is an easily oxidized neurotransmitter that is found throughout the brain. Considerable evidence suggests that it plays an important role in neurocircuitry related to fear and anxiety responses. In certain subregions of the bed nucleus of the stria terminalis (BNST), NE is found in large amounts. In this work we probed differences in electrically evoked release of NE and its regulation by the norepinephrine transporter (NET) and the α2-adrenergic autoreceptor (α2-AR) in two regions of the BNST of anesthetized rats. NE was monitored in the dorsomedial BNST (dmBNST) and ventral BNST (vBNST) by fast-scan cyclic voltammetry at carbon fiber microelectrodes. Pharmacological agents were introduced either by systemic application (intraperitoneal injection) or by local application (iontophoresis). The iontophoresis barrels were attached to a carbon fiber microelectrode to allow simultaneous detection of evoked NE release and quantitation of iontophoretic delivery. Desipramine (DMI), an inhibitor of NET, increased evoked release and slowed clearance of released NE in both regions independent of the mode of delivery. However, the effects of DMI were more robust in the vBNST than in the dmBNST. Similarly, the α2-AR autoreceptor inhibitor idazoxan (IDA) enhanced NE release in both regions but to a greater extent in the vBNST by both modes of delivery. Since both local application by iontophoresis and systemic application of IDA had similar effects on NE release, our results indicate that terminal autoreceptors play a predominant role in the inhibition of subsequent release.

scholarly journals Distributed and multifaceted effects of threat and safety

2021 ◽  
Author(s):  
Kelly Morrow ◽  
Dinavahi V P S Murty ◽  
Jongwan Kim ◽  
Songtao Song ◽  
Kesong Hu ◽  
...  
Keyword(s):  
Stria Terminalis ◽  
Functional Magnetic Resonance ◽  
Magnetic Resonance Study ◽  
Bed Nucleus ◽  
Aversive Events ◽  
Fmri Study ◽  
Anticipatory Processing ◽  
Small Set ◽  
The Impact ◽  
The Brain

Sustained anticipation of unpredictable aversive events generates anticipatory processing that is central to anxiety. In the present functional Magnetic Resonance Study (fMRI) study, we examined how sustained threat is processed in the human brain. We used a relatively large sample (N = 109) and employed a Bayesian multilevel analysis approach to contrast threat and safe periods. Our analyses demonstrated that the effect of sustained threat is heterogeneous and distributed across the brain. Thus, the impact of threat is widespread, and not restricted to a small set of putatively emotion-related regions, such as the amygdala and the bed nucleus of the stria terminalis. Both transient and sustained, and increased and decreased responses during threat were observed. Our study reveals that transitioning between threat and safe states, and vice versa, leads to a widespread switch in brain responding that involves most of the brain.

scholarly journals Cannabinoid Receptors in the Bed Nucleus of the Stria Terminalis Control Cortical Excitation of Midbrain Dopamine Cells In Vivo

2008 ◽  
Vol 28 (42) ◽  
pp. 10496-10508 ◽  
Author(s):  
L. Massi ◽  
I. Elezgarai ◽  
N. Puente ◽  
L. Reguero ◽  
P. Grandes ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Cortical Excitation ◽  
Midbrain Dopamine
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