The anterior cingulate cortex and its role in controlling contextual fear memory to predatory threats

Miguel Antonio Xavier De Lima,Newton Sabino Canteras,Marcus Vinicius C Baldo,Fernando A Oliveira

doi:10.7554/elife.67007

Miguel Antonio Xavier De Lima, Newton Sabino Canteras + Show 2 more

Open Access

https://doi.org/10.7554/elife.67007

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Journal: eLife	Publication Date: Jan 5, 2022
Citations: 22	License type: CC BY 4.0

Affiliation: Universidade de São Paulo, Universidade Federal do ABC

Abstract

Predator exposure is a life-threatening experience and elicits learned fear responses to the context in which the predator was encountered. The anterior cingulate area (ACA) occupies a pivotal position in a cortical network responsive to predatory threats, and it exerts a critical role in processing fear memory. The experiments were made in mice and revealed that the ACA is involved in both the acquisition and expression of contextual fear to predatory threat. Overall, the ACA can provide predictive relationships between the context and the predator threat and influences fear memory acquisition through projections to the basolateral amygdala and perirhinal region and the expression of contextual fear through projections to the dorsolateral periaqueductal gray. Our results expand previous studies based on classical fear conditioning and open interesting perspectives for understanding how the ACA is involved in processing contextual fear memory to ethologic threatening conditions that entrain specific medial hypothalamic fear circuits.

Highlights

Predator exposure is a life-threatening experience and elicits innate fear behaviors as well as learned fear responses to the context in which the predator was encountered (Blanchard et al, 1989; Blanchard et al, 2001; Ribeiro-Barbosa et al, 2005)
To evaluate the contribution of the anterior cingulate area (ACA) in the acquisition and expression of contextual fear to a predatory threat, we used designer receptors exclusively activated by designer drug (DREADD) to selectively silence the activity of the ACA during the cat exposure and during the exposure to the predatory context (Figure 1)
Patch-clamp experiments showed that transfected neurons (Gi-DREADD neurons) were hyperpolarized as they underwent de Lima et al eLife 2022;11:e67007

Summary

Introduction

Predator exposure is a life-threatening experience and elicits innate fear behaviors as well as learned fear responses to the context in which the predator was encountered (Blanchard et al, 1989; Blanchard et al, 2001; Ribeiro-Barbosa et al, 2005). Lesions in the ACA had a larger impact on decreasing learned contextual fear responses versus lesions of the other elements of this cortical network (de Andrade Rufino et al, 2019) At this point, it is not clear how the ACA is involved in processing predator-related fear memory. Using optogenetic silencing and functional tracing combining Fluoro Gold and Fos immunostaining, we examined how the ACA entrains selected targets to influence acquisition or expression of predator fear memory. The ACA offers predictive relationships between the threatening stimuli and the context to influence memory storage in amygdalar and hippocampal circuits It has a role in memory retrieval and the expression of contextual fear. Our results open interesting perspectives for understanding how the ACA is involved in processing contextual fear memory to predator threats as well as other ethologic threatening conditions such as those seen in the confrontation with a conspecific aggressor during social disputes

Results

Discussion

Materials and methods