Yue Wang1 · Naizheng Liu1 · Longyu Ma1 · Lupeng Yue4,5 · Shuang Cui1 · Feng‑Yu Liu1 · Ming Yi1,2 · You Wan1,2,31 Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, China
2 Key Laboratory for Neuroscience, Ministry of Education/National Health Commission, Peking University, Beijing 100083, China
3 Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226019, China
4 CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China
5 Department of Psychology, University of Chinese Academy of Sciences, Beijing 100101, China
Abstract
As a main structure of the limbic system, the hippocampus plays a critical role in pain perception and chronicity. The ventral hippocampal CA1 (vCA1) is closely associated with negative emotions such as anxiety, stress, and fear, yet how vCA1 neurons encode nociceptive information remains unclear. Using in vivo electrophysiological recording, we characterized vCA1 pyramidal neuron subpopulations that exhibited inhibitory or excitatory responses to plantar stimuli and were implicated in encoding stimuli modalities in naïve rats. Functional heterogeneity of the vCA1 pyramidal neurons was further identified in neuropathic pain conditions: the proportion and magnitude of the inhibitory response neurons paralleled mechanical allodynia and contributed to the confounded encoding of innocuous and noxious stimuli, whereas the excitatory response neurons were still instrumental in the discrimination of stimulus properties. Increased theta power and theta-spike coupling in vCA1 correlated with nociceptive behaviors. Optogenetic inhibition of vCA1 pyramidal neurons induced mechanical allodynia in naïve rats, whereas chemogenetic reversal of the overall suppressed vCA1 activity had analgesic effects in rats with neuropathic pain. These results provide direct evidence for the representations of nociceptive information in vCA1.
Keywords
Ventral hippocampal CA1; Nociception; Mechanical allodynia; In vivo recording; Neural coding
