Synaptic Plasticity Of Hippocampal CA1 NonCS Pathway During Reward Associative Learning

Hippocampus is considered to play a key role in online acquisition and short-term storage of declarative memory.Understanding the real-time memory encoding of information by hippocampus during learning and memory is an important way to reveal the memory mechanism of the brain.Long-term potentiation(LTP)is considered to be closely related to learning and memory.In the past,most of the studies have focused on in vitro experiments,and few observations have been made on real-time changes in hippocampal synaptic plasticity during learning.Employing electrophysiological recording during tone-water pairing training of medium difficulty,we previously observed the real-time changes of hippocampal CA1 synaptic plasticity,finding that LTP of the response to CS occurred in unilateral hippocampal CS transmission pathway,and that LTP of the response to electrode stimulus on i-Schaffer collateral / Association collateral also occurred in unilateral hippocampal non-CS transmission pathway(iSchaffer collateral / Association collateral).On this basis,in this paper we further explored the changes of the bilateral hippocampal CS transmission pathway and nonCS transmission pathway,as well as the specific changes of the non-CS transmission pathway.Research findings: 1 The recording of CS transmission pathway in bilateral hippocampal CA1 showed that LTP occurred on both sides,and that there was no difference,which demonstrates bilateral hippocampus participated in encoding cue information without lateralization;2.the response of CA1 non CS transmission pathway in the ipsilateral and contralateral hippocampus was recorded with electrode stimulus on only one side.We found that LTP occurred on both sides,and that there was no difference,which indicates that non CS transmission LTP may participate in the information coding of ipsilateral hippocampal CA1 and contralateral hippocampal CA1 at the same time;3.AC or SC pathway were selectively activated with optogenetic method instead of electrode to identifiy the components of LTP of non-CS transmission pathway.The results showed that LTP occured in AC pathway but not SC pathway,proving that AC pathway is the main participant of LTP of non-CS transmission pathway.4.To further explore the relationship between AC pathway and learning and memory,we analyzed the changes of synchronization in bilateral hippocampal CA1 brain regions during learning,finding that the synchronization of spontaneous electrical activity of brain in left and right hippocampal CA1 brain regions was enhanced,and that no significant difference was observed between the time point of synchronization increase and AC pathway LTP increase,indicating that the synchronization of left and right hippocampal CA1 was closely related to AC pathway LTP.Finally,we used 1 Hz optogenetic stimulation to interfere with bilateral hippocampal synchrony during learning,and found that the response of AC pathway was weakened,and the behavior of mice was affected,indicating that the increase of bilateral hippocampal synchrony and AC pathway LTP are necessary for the learning of mice.To sum up,our study shows that the left and right hippocampal CS transmission pathway and non-CS transmission pathway jointly participate in the learning and memory process and encode information.At the same time,the bilateral hippocampal non CS transmission pathway LTP is mainly AC pathway LTP,and this selective enhancement of AC pathway may be closely related to the synchronous enhancement of bilateral hippocampal CA1 activity,which is an important part of hippocampal physiological function of learning and memory.The results of this study provide a new insight for further understanding the coding rules of hippocampal information and its function of learning and memory.