A distinct cortical code for socially learned threat

• 成果类型: Article
• 署名作者: Silverstein, Shana E.; O'Sullivan, Ruairi; Bukalo, Olena; Pati, Dipanwita; Schaffer, Julia A.; Limoges, Aaron; Zsembik, Leo; Yoshida, Takayuki; O'Malley, John J.; Paletzki, Ronald F.; Lieberman, Abby G.; Nonaka, Mio; Deisseroth, Karl; Gerfen, Charles R.; Penzo, Mario A.; Kash, Thomas L.; Holmes, Andrew
• 署名单位: National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA); University of North Carolina; University of North Carolina Chapel Hill; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH); National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH); Stanford University; Stanford University; Stanford University; Howard Hughes Medical Institute
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6062
• DOI: 10.1038/s41586-023-07008-1
• 发表日期: 2024-02-29
• 关键词: medial prefrontal cortex; somatostatin interneurons; basolateral amygdala; ventral hippocampus; fear; inhibition; specificity; modulation; mechanisms; excitation

摘要

Animals can learn about sources of danger while minimizing their own risk by observing how others respond to threats. However, the distinct neural mechanisms by which threats are learned through social observation (known as observational fear learning1-4 (OFL)) to generate behavioural responses specific to such threats remain poorly understood. The dorsomedial prefrontal cortex (dmPFC) performs several key functions that may underlie OFL, including processing of social information and disambiguation of threat cues5-11. Here we show that dmPFC is recruited and required for OFL in mice. Using cellular-resolution microendoscopic calcium imaging, we demonstrate that dmPFC neurons code for observational fear and do so in a manner that is distinct from direct experience. We find that dmPFC neuronal activity predicts upcoming switches between freezing and moving state elicited by threat. By combining neuronal circuit mapping, calcium imaging, electrophysiological recordings and optogenetics, we show that dmPFC projections to the midbrain periaqueductal grey (PAG) constrain observer freezing, and that amygdalar and hippocampal inputs to dmPFC opposingly modulate observer freezing. Together our findings reveal that dmPFC neurons compute a distinct code for observational fear and coordinate long-range neural circuits to select behavioural responses. Studies in mice show that observational fear learning is encoded by neurons in the dorsomedial prefrontal cortex in a manner that is distinct from the encoding of fear learned by direct experience.