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Download Activation of CA3 neurons by optogenetic stimulation of mossy fiber
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Activation of CA3 neurons by optogenetic stimulation of mossy fiber terminals in behaving mice Joonyeup Lee1,2, Eunjae Cho2, Young Kang2, Jongwon Lee2, Min Whan Jung1,2 1 Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea 2 Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, Republic of Korea Despite extensive studies in in vitro preparations, it is unclear whether and how discharges of dentate gyrus (DG) granule cells shape spatial firing of CA3 neurons in behaving animals. To investigate effects of DG granule cell inputs on CA3 neural activity in vivo, we injected Credependent virus carrying a channelrhodopsin-2 variant (ChETA) to the dorsal DG of Rbp4Cre mice. The mice were trained to run on a circular track in one direction to obtain water reward at two opposite locations. We then implanted an optical fiber and an array of tetrodes in the CA3 region, and examined effects of stimulating mossy fiber terminals on spatial firing of CA3 neurons. We found that some CA3 neurons were reliably activated or inactivated by optogenetic stimulation of mossy fiber terminals. As a consequence, their spatial firing on the track was altered during optogenetic stimulation. These results indicate that optogenetic stimulation of mossy fiber terminals can drive discharges and influence spatial firing of CA3 neurons in behaving animals. Since our light stimulation presumably affects a large number of mossy fiber terminals simultaneously, it would be premature to link our findings to the effect of granule cell discharges on CA3 neural activity under natural conditions. To address this issue, examining effects of inactivating DG granule cell inputs on CA3 neuronal activity is currently under way.