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

TL;DR

The study shows that different groups of cholinergic neurons in the mouse brain handle different types of threat memories.

Contribution

The paper identifies distinct cholinergic neuron populations encoding learned and innate threat memories in mice.

Findings

BLA-projecting cholinergic neurons learn and recall conditioned threat memories.

VP/SIa cholinergic neurons respond to innate threats like predator odor.

Learning-activated neurons are essential for expressing defensive behaviors.

Abstract

Neurons of the basal forebrain nucleus basalis and posterior substantia innominata (NBM/SIp) 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 naïve tone and a foot shock (training) and release ACh in the BLA in response to the conditioned tone 24h later (recall). In the NBM/SIp 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/SIp cholinergic neurons are not activated by an innately threatening stimulus (predator odor). Instead, VP/SIa 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.

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