Anterior cingulate cortex and its input to the basolateral amygdala control innate fear response

Jinho Jhang,Han-Sol Lee,Jin-Hee Han,Min Soo Kang,Hyungju Park,Hyoeun Lee

doi:10.1038/s41467-018-05090-y

Abstract

Prefrontal brain areas are implicated in the control of fear behavior. However, how prefrontal circuits control fear response to innate threat is poorly understood. Here, we show that the anterior cingulate cortex (ACC) and its input to the basolateral nucleus of amygdala (BLA) contribute to innate fear response to a predator odor in mice. Optogenetic inactivation of the ACC enhances freezing response to fox urine without affecting conditioned freezing. Conversely, ACC stimulation robustly inhibits both innate and conditioned freezing. Circuit tracing and slice patch recordings demonstrate a monosynaptic glutamatergic connectivity of ACC-BLA but no or very sparse ACC input to the central amygdala. Finally, our optogenetic manipulations of the ACC-BLA projection suggest its inhibitory control of innate freezing response to predator odors. Together, our results reveal the role of the ACC and its projection to BLA in innate fear response to olfactory threat stimulus.

Highlights

Prefrontal brain areas are implicated in the control of fear behavior
For anterior cingulate cortex (ACC) photoinhibition, adeno-associated viral (AAV) vectors encoding halorhodopsin-3.0 fused with enhanced yellow fluorescence protein or green fluorescence protein as a control under control of the CaMKIIα promoter were injected into the bilateral ACC
Mice injected with AAV-eNpHR3.0 or AAV-eGFP were trained for auditory fear conditioning in which an auditory tone as a CS was paired with a foot shock as an unconditioned stimulus (US), and 24 h later mice were re-exposed to the tone CS in a different context (Fig. 1c)

Summary

Introduction

Prefrontal brain areas are implicated in the control of fear behavior. how prefrontal circuits control fear response to innate threat is poorly understood. Consistent with a possible role of the ACC in regulating fear behavior, anatomical analyses of rodent brains using neural circuit tracing techniques, such as injection of anterograde or retrograde tracers (e.g., fluorescent tracer dyes, horseradish peroxidase-wheat germ agglutinin (WGA), and Phaseolus vulgaris leucoagglutinin)[16,18,19,20], show that the ACC sends a strong projection to the BLA, which is involved in the regulation of fear responses to threats[21,22]. The expression of place aversion is shown to be normal in animals with ACC lesions[25] Despite these results suggesting that the ACC may not play a critical role in the expression of learned fear in rodents, the role of the ACC and its projection to the BLA in regulating fear responses to innate threat is unknown. We report that the ACC input to the BLA contributes to determine innate fear response

Methods

Results

Conclusion