Title

Basal Forebrain and Brainstem Cholinergic Neurons Differentially Impact Amygdala Circuits and Learning-Related Behavior

Document Type

Article

Publication Date

8-20-2018

Journal

Current Biology

Volume

28

Issue

16

First Page

2557

Last Page

2569.e4

URL with Digital Object Identifier

10.1016/j.cub.2018.06.064

Abstract

© 2018 Elsevier Ltd The central cholinergic system and the amygdala are important for motivation and mnemonic processes. Different cholinergic populations innervate the amygdala, but it is unclear how these projections impact amygdala processes. Using optogenetic circuit-mapping strategies in choline acetyltransferase (ChAT)-cre mice, we demonstrate that amygdala-projecting basal forebrain and brainstem ChAT-containing neurons can differentially affect amygdala circuits and behavior. Photo-activating ChAT terminals in vitro revealed the underlying synaptic impact of brainstem inputs to the central lateral division to be excitatory, mediated via the synergistic glutamatergic activation of AMPA and NMDA receptors. In contrast, stimulating basal forebrain inputs to the basal nucleus resulted in endogenous acetylcholine (ACh) release, resulting in biphasic inhibition-excitation responses onto principal neurons. Such response profiles are physiological hallmarks of neural oscillations and could thus form the basis of ACh-mediated rhythmicity in amygdala networks. Consistent with this, in vivo basal forebrain ChAT+ activation strengthened amygdala basal nucleus theta and gamma frequency rhythmicity, both of which continued for seconds after stimulation and were dependent on local muscarinic and nicotinic receptor activation, respectively. Activation of brainstem ChAT-containing neurons, however, resulted in a transient increase in central lateral amygdala activity that was independent of cholinergic receptors. In addition, driving these respective inputs in behaving animals induced opposing appetitive and defensive learning-related behavioral changes. Because learning and memory are supported by both cellular and network-level processes in central cholinergic and amygdala networks, these results provide a route by which distinct cholinergic inputs can convey salient information to the amygdala and promote associative biophysical changes that underlie emotional memories. Aitta-aho et al. show that different cholinergic neuronal populations projecting to distinct amygdala nuclei coordinate local circuits and can reinforce approach and avoidance behavior. These results reveal separate mechanisms by which ACh populations can engage processes for inducing biophysical changes that underlie emotional memories.

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