Threat imminence dictates the role of the bed nucleus of the stria terminalis in contextual fear

Abstract

Recent work indicates that the bed nucleus of the stria terminalis (BNST) is critically involved in the regulation of conditioned fear responses to unpredictable threats. Here we examined whether the involvement of the BNST in contextual fear conditioning in male rats depends on the imminence of shock after placement in the conditioning chamber. Specifically, we hypothesized that the BNST supports contextual freezing after conditioning with delayed, but not imminent, footshock (relative to placement in the context). Rats were implanted with cannulae targeting the BNST and underwent a contextual fear conditioning procedure in which a single footshock unconditioned stimulus (US) was delivered either 1 minute or 9 minutes after the rat was placed in the context; the rats received a total of four identical conditioning sessions over two days, all with equivalent exposure to the context. Contexts associated with either imminent or delayed US onsets produced distinct patterns of freezing and shock-induced activity but freezing in each case was context-dependent. Reversible inactivation of the BNST reduced the expression of contextual freezing in the context paired with delayed (9 min), but not imminent (1 min), footshock onset. Implications of these data are discussed in the light of recent conceptualizations of BNST function, as well as for anxiety behaviors.

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

“…The BNST, meanwhile, supports learning in the absence of the BLA ( Poulos et al, 2010 ; Zimmerman and Maren, 2011 ), and when a stimulus poorly predicts threat ( Lebow and Chen, 2016 ; Goode et al, 2019 ; Bjorni et al, 2020 ), either because it is distal (e.g., predator odor; Fendt et al, 2003 ; Xu et al, 2012 ; Breitfeld et al, 2015 ; Verma et al, 2018 ; Goode et al, 2020 ), diffuse (e.g., contextual; Sullivan et al, 2004 ; Kalin et al, 2005 ; Duvarci et al, 2009 ; Davis et al, 2010 ; Luyten et al, 2012 ; Jennings et al, 2013 ; c.f. Haufler et al, 2013 ), or temporally ambiguous (e.g., random or sustained; Waddell et al, 2006 ; Walker et al, 2009 ; Hammack et al, 2015 ; Daldrup et al, 2016 ; Goode and Maren, 2017 ; Lange et al, 2017 ) with respect to the US.…”

Oxytocin Promotes Accurate Fear Discrimination and Adaptive Defensive Behaviors

“…The BLA sends excitatory inputs also to the BNST (Gungor and Pare, 2016) and growing evidence suggests that the BNST plays a major role in the modulation of fear discrimination (Duvarci et al, 2009;Goode et al, 2019Goode et al, , 2020Janeček and Dabrowska, 2019;Martinon et al, 2019). Male rats with BNST lesions were trained in a discriminatory auditory fear conditioning paradigm (paired CS+ vs un-paired CS−) and showed significantly improved fear discrimination during fear recall test, such that they responded primarily to the CS+ while showing significantly reduced responses to CS− (Duvarci et al, 2009).…”

Reducing shock imminence eliminates poor avoidance in rats

“…There are far more studies of US imminence using Pavlovian paradigms. These suggest that threats activate different components of the survival circuit depending on proximity to harm (modeled by CS-US delay; Walker and Davis 1997;Davis 1998;Sullivan et al 2004;Waddell et al 2006;Mobbs et al 2007Mobbs et al , 2009Goode et al 2020). Short-duration CSs recruit amygdala and periaqueductal gray to emit short-latency, inflexible, hard-wired responses that function to prevent threat escalation (e.g., freezing, a postencounter response) or escape harm (e.g., flight, a circa-strike response).…”