Dr. Marina Picciotto is the Charles BG Murphy Professor of Psychiatry, Deputy Chair for Basic Science, Director of the Division of Molecular Psychiatry and professor in the departments of Neuroscience, Pharmacology and in the Child Study Center at Yale University. Dr. Picciotto’s laboratory works on the neurobiology underlying typical behaviors and those relevant to human psychiatric illness using laboratory mice, as well as translating these basic findings to human subjects. She was one of 60 young US scientists awarded the Presidential Early Career Award for Scientists and Engineers by President Clinton in 2000, was elected to the National Academy of Medicine in 2012, was awarded the Carnegie Prize in Mind and Brain Sciences in 2020, and recently won the 2021 Langley Award for fundamental research related to nicotine and tobacco.
Stress-induced acetylcholine signaling in the hippocampus: too much of a good thing?
Acetylcholine (ACh) is a critical neurotransmitter for communication in the autonomic nervous system and in the brain. We know that stress increases release of ACh and that pharmacological blockade of ACh breakdown induces symptoms of depression in human subjects and increases stress-related behaviors in rodents. We have found that manipulations of ACh signaling in hippocampus is sufficient to recapitulate effects of systemic modulation of the cholinergic system on stress-induced behaviors in mice. By altering cholinergic input to the hippocampus using chemogenetic and optogenetic strategies, coupled with pharmacological approaches, we demonstrate that ACh signaling from the medial septum to the dorsal and ventral hippocampus increases susceptibility for behavioral responses to acute and chronic stress in mice. These data demonstrate that ACh signaling in the hippocampus is critical for mediating behavioral responses to stressful stimuli and support the hypothesis that dysregulated ACh signaling contributes to stress-related disorders in depressed patients.