Cortical cholinergic signaling is implicated in diverse functions, including arousal and vigilance, signaling of reinforcements, and learning and memory. There is also evidence suggesting cholinergic contributions to value-based decisions. However, decision-making is an elaborate process, influenced by parameters such as value functions, learning rates, reward prediction errors, and so on. Still poorly understood is the extent to which cholinergic signaling may report or regulate specific decision-related parameters. In preliminary studies, we developed a novel adaptation of a value-based decision-making task for head-fixed mice. Analysis and reinforcement learning model fit of the task performance indicate behavior consistent with value-based decisions. In this proposal, we will determine the neural encoding in cortical cholinergic axons by measuring their activity dynamics in the rodent premotor cortex during decision-making (Aim 1). We will determine the influence of fast cholinergic signaling on value-based decisions by manipulating acetylcholine release in the neocortex (Aim 2). Because neuromodulators such as acetylcholine have considerable influence on multiple facets of decision-making, the proposed studies to delineate its computational function will provide insights into the neural basis of value-based decisions.

Public Health Relevance

Acetylcholine is a neuromodulator implicated in diverse functions. We propose to determine the function of acetylcholine release in the frontal cortex in mice performing a dynamic foraging task. The results may provide insights into the neural computation of value-based decisions and its impairments in health and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21MH118596-01
Application #
9647773
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Rossi, Andrew
Project Start
2018-09-21
Project End
2020-07-31
Budget Start
2018-09-21
Budget End
2019-07-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
Atilgan, Huriye; Kwan, Alex C (2018) Same lesson, varied choices by frontal cortex. Nat Neurosci 21:1648-1650