Xu Han, Yuan Haoyang, Song Hengyi, Pan Yunlong, Wu Zhouyue, Wang Shuaishuai, Cheng Jiawen, Luo Yifan, Lin Lishan, Min Pengxiang, Yue Yue, Chen Xiang, Zhang Kezhong, Fukunaga Kohji, Sasaki Takuya, Mao Xingfeng, Han Feng, Lu Ying-Mei
Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Nanjing, China; International Joint Laboratory for Drug Target of Critical Illnesses, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
Key Laboratory of Modern Toxicology of Ministry of Education, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China.
Cell Rep. 2025 Sep 8;44(9):116255. doi: 10.1016/j.celrep.2025.116255.
Neurons that encode odor information are fundamental to innate fear processes, yet how mitral/tufted (M/T) cells encode innate fear remains unknown. Here, we identify three different response patterns of M/T cells in the dorsal olfactory bulb (dOB) during active avoidance elicited by non-dehydrogenated 2,4,5-trimethylthiazole (nTMT) through in vivo calcium imaging and multielectrode recordings in mice, including enhanced responses, suppressed responses, and no response. Remarkably, suppressed response M/T cells encode active avoidance, whereas suppressed and enhanced response M/T cells jointly encode passive freezing. Our results show that cyclin-dependent kinase 5 (Cdk5) deficiency reduces the mean firing rate (MFR) of M/T cells and alters the intrinsic encoding patterns of M/T cells in nTMT-induced abnormal avoidance and freezing behaviors, and these changes can be rescued by activating dOB M/T cells. These results reveal multimodal neural population coding characteristics of innate fear in the dOB.
编码气味信息的神经元是先天恐惧过程的基础，但二尖瓣/簇状（M/T）细胞如何编码先天恐惧仍不清楚。在这里，我们通过体内钙成像和小鼠多电极记录，确定了在非脱氢2,4,5-三甲基噻唑（nTMT）引发的主动回避过程中，背侧嗅球（dOB）中M/T细胞的三种不同反应模式，包括增强反应、抑制反应和无反应。值得注意的是，抑制反应的M/T细胞编码主动回避，而抑制和增强反应的M/T细胞共同编码被动僵住。我们的结果表明，细胞周期蛋白依赖性激酶5（Cdk5）缺陷会降低M/T细胞的平均放电率（MFR），并改变nTMT诱导的异常回避和僵住行为中M/T细胞的内在编码模式，并且这些变化可以通过激活dOB M/T细胞来挽救。这些结果揭示了dOB中先天恐惧的多模态神经群体编码特征。
