Hippocampal Interneurons are Required for Trace Eyeblink Conditioning in Mice
Wei-Wei Zhang1 • Rong-Rong Li1 • Jie Zhang1 • Jie Yan1 • Qian-Hui Zhang2 • Zhi-An Hu1 • Bo Hu1,3 • Zhong-Xiang Yao1 • Hao Chen4
1 Department of Physiology, College of Basic Medical Sciences, Army Medical University, Chongqing 400038, China
2 Department of Foreign Language, College of Basic Medical Sciences, Army Medical University, Chongqing 400038, China
3 Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Army Medical University, Chongqing 400038, China
4 Experimental Center of Basic Medicine, College of Basic Medical Sciences, Army Medical University, Chongqing 400038, China
Abstract
While the hippocampus has been implicated in supporting the association among time-separated events, the underlying cellular mechanisms have not been fully clarified. Here, we combined in vivo multi-channel recording and optogenetics to investigate the activity of hippocampal interneurons in freely-moving mice performing a trace eyeblink conditioning (tEBC) task. We found that the hippocampal interneurons exhibited conditioned stimulus (CS)-evoked sustained activity, which predicted the performance of conditioned eyeblink responses (CRs) in the early acquisition of the tEBC. Consistent with this, greater proportions of hippocampal pyramidal cells showed CS-evoked decreased activity in the early acquisition of the tEBC. Moreover, optogenetic suppression of the sustained activity in hippocampal interneurons severely impaired acquisition of the tEBC. In contrast, suppression of the sustained activity of hippocampal interneurons had no effect on the performance of well-learned CRs. Our findings highlight the role of hippocampal interneurons in the tEBC, and point to a potential cellular mechanism subserving associative learning.
Keywords
Hippocampus; Interneuron; Trace eyeblink conditioning; Sustained activity; Associative learning