Functionally refined encoding of threat memory by distinct populations of basal forebrain cholinergic projection neurons
- National Institute of Neurological Disorders and Stroke, United States
- Yale University, United States
- Kansas City University of Medicine and Biosciences, United States
- LinkedIn, United States
- National Institute of Environmental Health Sciences, United States
- Steris, United States
- Peking University, China
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.
Data availability
Source data for the fiber photometry experiments presented in Figure 1 and supplements are provided as individual source data files.
Article and author information
Author details
Prithviraj Rajebhosale
Marina R Picciotto
Funding
National Institute of Neurological Disorders and Stroke (1ZIANS009424)
- David A Talmage
National Institute of Neurological Disorders and Stroke (1ZIANS009416,1ZIANS009422)
- Lorna W Role
National Institute of Neurological Disorders and Stroke (NS22061)
- Lorna W Role
- David A Talmage
National Institute of Mental Health (U01-MH109104)
- Lorna W Role
- David A Talmage
National Institute of Mental Health (MH077681)
- Marina R Picciotto
National Institute on Drug Abuse (DA14241,DA037566)
- Marina R Picciotto
National Institute of Neurological Disorders and Stroke (NS007224)
- Richard B Crouse
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Joshua Johansen, RIKEN Center for Brain Science, Japan
Ethics
Animal experimentation: All animal care and experimental procedures were approved by the Animal Care and Use Committees (ACUC) of the National Institute of Neurological Disorders & Stroke (NINDS) (Protocol #1531), SUNY Research Foundation at Stony Brook University (Protocol #1618), and Yale University (Protocol #2019-07895).
Version history
- Preprint posted: May 3, 2021 (view preprint)
- Received: February 1, 2023
- Accepted: February 14, 2024
- Accepted Manuscript published: February 16, 2024 (version 1)
- Version of Record published: March 11, 2024 (version 2)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Functionally refined encoding of threat memory by distinct populations of basal forebrain cholinergic projection neurons
eLife 13:e86581.
https://doi.org/10.7554/eLife.86581
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