美国国家酒精滥用和酒精中毒研究所Andrew Holmes等研究人员合作发现大脑皮层对社会习得威胁的独特编码。相关论文于2024年2月7日在线发表在《自然》杂志上。

研究人员表示，动物可以通过观察他人如何应对威胁来了解危险来源，同时将自身风险降至最低。然而，人们对通过社会观察了解威胁（称为观察性恐惧学习，OFL），从而产生针对这些威胁的特定行为反应的独特神经机制仍然知之甚少。背内侧前额叶皮层（dmPFC）具有可能是观察性恐惧学习基础的几种关键功能，包括处理社会信息和消除威胁线索。

研究人员证明了小鼠的OFL需要招募dmPFC。利用细胞分辨率微内窥镜钙成像技术，研究人员证明了dmPFC神经元为观察性恐惧编码，而且编码的方式有别于直接经验。研究人员发现，dmPFC神经元的活动可以预测威胁即将引起的冻结和移动状态之间的切换。通过结合神经元回路映射、钙成像、电生理记录和光遗传学，研究人员发现，dmPFC向中脑导水管周围灰质（PAG）的投射限制了观察者的冻结，而杏仁核和海马对dmPFC的输入则相反地调节观察者的冻结。这些研究结果共同揭示，dmPFC神经元为观察性恐惧计算不同的代码，并协调长程神经回路以选择行为反应。

附：英文原文

Title: A distinct cortical code for socially learned threat

Author: Silverstein, Shana E., OSullivan, Ruairi, Bukalo, Olena, Pati, Dipanwita, Schaffer, Julia A., Limoges, Aaron, Zsembik, Leo, Yoshida, Takayuki, OMalley, John J., Paletzki, Ronald F., Lieberman, Abby G., Nonaka, Mio, Deisseroth, Karl, Gerfen, Charles R., Penzo, Mario A., Kash, Thomas L., Holmes, Andrew

Issue&Volume: 2024-02-07

Abstract: 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 learning1,2,3,4 (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 cues5,6,7,8,9,10,11. 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.

DOI: 10.1038/s41586-023-07008-1

Source: https://www.nature.com/articles/s41586-023-07008-1