Amygdalostriatal transition zone neurons encode sustained cue responses to guide defensive behaviors
Year: 2026
Type: article
Abstract: SUMMARY To ensure survival, the brain must rapidly identify threats and maintain defensive behaviors for as long as danger is present. The amygdala has been studied as a key site for fear responses, but responses to threat cues in amygdala neurons are largely transient and shorter in duration than defensive responses observed. Here, we present the amygdalostriatal transition zone (ASt) as a missing piece of the circuits mediating fear responses. Using single-nucleus RNA sequencing (snRNA-seq), we demonstrate that the ASt is genetically distinct from adjacent striatal and amygdalar structures. In vivo electrophysiology and calcium imaging reveal that ASt neurons have robust, sustained responses to shock-predicting cues. Further, photostimulation of the ASt is sufficient to drive freezing and avoidance behaviors, and optogenetic inhibition experiments show that Drd2+ ASt neurons are necessary for cue-conditioned fear responses. Our findings establish the ASt as a previously unappreciated yet critical structure for encoding learned associations and directing defensive behaviors. HIGHLIGHTS ASt neurons have a unique genetic identity ASt neurons encode sustained responses to conditioned shock cues Activation of ASt neurons is sufficient to drive freezing and avoidance Drd2+ ASt neurons are necessary for expression of cued fear responses
Source: Neuron
Authors: Fergil Mills, Christopher R. Lee, James R. Howe, Hao Li, Maria N. Keisler, Shan Shao, Felix H. Taschbach, Mackenzie E. Lemieux, Faith Aloboudi, Jesse White, May G. Chan, Matilde Borio, Laurel R. Keyes, Hannah S. Chen, Fabiha Bushra, Gates P. Schneider, Dani P. Lemmon, Kyung J. Lee, Alexa L. Gross, Kanha Batra, Reesha R. Patel, Meenakshi M. Asokan, Jeremy Delahanty, Christian Cazares, Christopher R. Heyman, Nicholas B. Poll, Liezl Maree, Romy Wichmann, Talmo D. Pereira, Marcus K. Benna, Cory M. Root, Kay M. Tye
Language: English
Topic: Memory and Neural Mechanisms
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Funders: Howard Hughes Medical Institute, Kavli Foundation, New York Stem Cell Foundation, McKnight Foundation, Klingenstein Third Generation Foundation, Salk Institute for Biological Studies, Dolby Family Ventures, China Scholarship Council, National Institutes of Health, Canadian Institutes of Health Research, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Center for Complementary and Integrative Health
Awards: Multispectral, high speed, super-resolution confocal microscopy system to support research in complex neurobiology, Neural Circuit Mechanisms of Social Homeostasis in Individuals and Supraorganismal Social Groups, Determining how neurotensin mediates valence processing and compulsive cocaine seeking, San Diego Nathan Shock Center, Determining the role of amygdalostriatal transition zone circuits in associative learning and motivated behaviors, Exploring neural circuit mechanisms of social contact and social isolation, Corticolimbic Neuroimmune Determinants of Social Stress-Associated Alcohol Drinking, Developing multimodal biomarkers of cognitive ability in a genetic model of neurodevelopment, Solving the Valence Assignment Problem, Cancer Center Support Grant (CCSG)
OpenAlex ID: W7213115916