Adrenergic Signalling to Astrocytes in Anterior Cingulate Cortex Contributes to Pain-related Aversive Memory in Rats

Overview

Journal Commun Biol

Specialty Biology

Date 2023 Jan 5

PMID 36604595

Authors

Zafar Iqbal

Zhuogui Lei

Aruna S Ramkrishnan

Shu Liu

Mahadi Hasan

Mastura Akter

Yuk Yan Lam

Ying Li

Affiliations

Soon will be listed here.

Abstract

Pain contains both sensory and affective dimensions. We identify the role of norepinephrine in colorectal distention (sub-threshold for acute pain) induced conditioned place avoidance and plasticity gene expression in the anterior cingulate cortex (ACC). Activating locus coeruleus (LC)-projecting ACC neurons facilitates pain-evoked aversive consolidation and memory, while inhibiting LC-projecting ACC neurons reversibly blocks it. Optogenetic activation of ACC astrocytes facilitates aversive behaviour. ACC astrocytic Gi manipulation suppressed aversive behaviour and early plasticity gene expression induced by opto-activation of LC neurons projecting to ACC. Evidences for the critical role of β2AR in ACC astrocytes were provided using AAV encoding β2AR miRNAi to knockdown β2AR in astrocytes. In contrast, opto-activation of ACC astrocytic β2ARs promotes aversion memory. Our findings suggest that projection-specific adrenergic astrocytic signalling in ACC is integral to system-wide neuromodulation in response to visceral stimuli, and plays a key role in mediating pain-related aversion consolidation and memory formation.

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