Reversible Inactivation of the Bed Nucleus of the Stria Terminalis Prevents Reinstatement But Not Renewal of Extinguished Fear

ABSTRACTPrevious work indicates that the bed nucleus of the stria terminalis (BNST) is involved in defensive freezing to unpredictable Pavlovian conditioned stimuli (Goode et al., 2019). Here we show that the BNST mediates freezing to contexts paired with remote (unpredictable), but not imminent (predictable), footshock. Rats underwent a fear conditioning procedure in which a single footshock unconditioned stimulus (US) was delivered either 1 (imminent) or 9 minutes (remote) after placement in the context; each rat received a total of four conditioning trials over two days. Contexts associated with either imminent or remote USs 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 remote, but not imminent, footshock. Implications of these data are discussed in light of recent conceptualizations of BNST function, as well as for anxiety behaviors.

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Bed nucleus of the stria terminalis regulates fear to unpredictable threat signals

eLife ◽

10.7554/elife.46525 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 15

Author(s):

Travis D Goode ◽

Reed L Ressler ◽

Gillian M Acca ◽

Olivia W Miles ◽

Stephen Maren

Keyword(s):

Conditioned Fear ◽

Stria Terminalis ◽

Conditioned Stimuli ◽

Variable Intensity ◽

Reversible Inactivation ◽

Bed Nucleus ◽

Defensive Behaviors ◽

The Us ◽

Specific Factors ◽

Fear And Anxiety

The bed nucleus of the stria terminalis (BNST) has been implicated in conditioned fear and anxiety, but the specific factors that engage the BNST in defensive behaviors are unclear. Here we examined whether the BNST mediates freezing to conditioned stimuli (CSs) that poorly predict the onset of aversive unconditioned stimuli (USs) in rats. Reversible inactivation of the BNST selectively reduced freezing to CSs that poorly signaled US onset (e.g., a backward CS that followed the US), but did not eliminate freezing to forward CSs even when they predicted USs of variable intensity. Additionally, backward (but not forward) CSs selectively increased Fos in the ventral BNST and in BNST-projecting neurons in the infralimbic region of the medial prefrontal cortex (mPFC), but not in the hippocampus or amygdala. These data reveal that BNST circuits regulate fear to unpredictable threats, which may be critical to the etiology and expression of anxiety.

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Bed nucleus of the stria terminalis regulates fear to unpredictable threat signals

10.1101/376228 ◽

2018 ◽

Cited By ~ 2

Author(s):

Travis D. Goode ◽

Reed L. Ressler ◽

Gillian M. Acca ◽

Olivia W. Miles ◽

Stephen Maren

Keyword(s):

Conditioned Fear ◽

Stria Terminalis ◽

Variable Intensity ◽

Reversible Inactivation ◽

Bed Nucleus ◽

Defensive Behaviors ◽

The Us ◽

Specific Factors ◽

Fear And Anxiety ◽

Pathological Anxiety

ABSTRACTThe bed nucleus of the stria terminalis (BNST) has been implicated in conditioned fear and anxiety, but the specific factors that engage the BNST in defensive behaviors are unclear. Here we examined whether the BNST mediates freezing to conditioned stimuli (CSs) that poorly predict the onset of aversive unconditioned stimuli (USs) in rats. Reversible inactivation of the BNST selectively reduced freezing to CSs that poorly signaled US onset (e.g., a backward CS that followed the US), but did not eliminate freezing to forward CSs even when they predicted USs of variable intensity. Additionally, backward (but not forward) CSs selectively increased Fos in the ventral BNST and in BNST-projecting neurons in the infralimbic region of the medial prefrontal cortex (mPFC), but not in the hippocampus or amygdala. These data reveal that BNST circuits regulate fear to unpredictable threats, which may be critical to the etiology and expression of anxiety.IMPACT STATEMENTThe bed nucleus of the stria terminalis (BNST) is required for the expression of defensive behavior to unpredictable threats, a function that may be central to pathological anxiety.

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