Work

Author response: Functionally refined encoding of threat memory by distinct populations of basal forebrain cholinergic projection neurons

Year: 2023

Type: peer-review

Abstract: Neurons of the basal forebrain nucleus basalis and posterior substantia innominata (NBM/SI p ) comprise the major source of cholinergic input to the basolateral amygdala (BLA).Using a genetically encoded acetylcholine (ACh) sensor in mice, we demonstrate that BLA-projecting cholinergic neurons can 'learn' the association between a naive tone and a foot shock (training) and release ACh in the BLA in response to the conditioned tone 24 hr later (recall).In the NBM/ SI p cholinergic neurons express the immediate early gene, Fos following both training and memory recall.Cholinergic neurons that express Fos following memory recall display increased intrinsic excitability.Chemogenetic silencing of these learning-activated cholinergic neurons prevents expression of the defensive behavior to the tone.In contrast, we show that NBM/SI p cholinergic neurons are not activated by an innately threatening stimulus (predator odor).Instead, VP/SI a cholinergic neurons are activated and contribute to defensive behaviors in response to predator odor, an innately threatening stimulus.Taken together, we find that distinct populations of cholinergic neurons are recruited to signal distinct aversive stimuli, demonstrating functionally refined organization of specific types of memory within the cholinergic basal forebrain of mice. Editor's evaluationThis important study examines the existence of a specific population of memory encoding acetylcholine neurons of the basal forebrain which regulate the amygdala for fear expression.Using a combination of techniques including genetic access to c-Fos expressing neurons, in-vivo chemogenetics, and optical detection of acetylcholine (ACh), the authors present convincing evidence that posteriorly located amygdala projecting basal forebrain cholinergic neurons participate in cue-specific threat learning and memory.This paper will be of interest to those studying circuit-level mechanisms of learning and emotion regulation.

Source: eLife

DOI: 10.7554/elife.86581.sa2