A Study On The Relation Between The Non-targeted Lead LTP In Hippocampal CA1 And Memory And Behavior During Rewarding Associative Learning

Memory is an important part of brain functions,one of the advanced activities of the brain,which is essentially neuron structure-based signaling and processing.As a member of the limbic system,the hippocampus is mainly responsible for the acquisition and early storage of declarative memory.Neurons exhibit synaptic plasticity accompanying memory formation,especially in the form of long-term potentiation(LTP),which is widely regarded as the most likely physiological mechanism to memory formation.A large number of previous studies have focused on studying hippocampal synaptic plastic changes after learning by means of in vitro experiments or in vivo extracellular electrophysiological recording.Only few studies on synaptic plasticity are carried out during learning.A rewarding associative learning behavioral paradigm was established in this paper.We employed in vivo extracellular electrophysiological recording,optogenetics and brain drug delivery techniques to explore the simultaneous activities during learning process.The relationship between LTP in the conditional stimulus(CS)encoding pathways,in the non-targeted pathways and behavioral performance was investigated.In our previous studies employing local field potential(LFP)recording in hippocampal CA1 during tone-water pairing associative learning,CS-response LTP,that is,synaptic plastic changes in CS encoding pathways was observed.Evaluation of CA3-CA1 synaptic strength was also carried out by means of electrical stimulation on the hippocampal Schaffer collateral/associational commissural(SC/AC)pathway.An early LTP occurred in the SC / AC pathway,which was not in the CS and US encoding pathways.We found that the time and amplitude of this LTP,which we named the non-targeted lead LTP,are different from the CS-response LTP.We hypothesize that this non-targeted lead LTP plays a potential role in hippocampal memory encoding.To further investigate the relationship between the spatial and temporal occurrence of the non-targeted lead LTP and memory encoding,as well as its neural mechanism and physiological significance.We first repeated experiments described above,and consistent results were obtained.The non-targeted lead LTP started earlier than the appearance of behavioral conditioned response(CR)and CS-response LTP,and the time difference was 3-5 minutes.To further determine the spatiotemporal and causal relationship between the non-targeted lead LTP and the CS-response LTP,we designed a more difficult flash-water pairing rewarding associative learning task.Optogenetic technology was utilized to inhibit non-targeted lead LTP with low frequency stimulation(1 Hz),and the results showed that after the non-targeted lead LTP was dirupted,both the behavioral CR and CS-responsive LTP were affected.We concluded that early-untargeted LTP is necessary for learning.Finally,we investigated the molecular mechanisms underlying the non-targeted lead LTP by administering APV near the recording site of the hippocampal SC / AC pathway,finding that the non-targeted lead LTP depends on the NMDA receptors.In conclusion,our studies demonstrate real-time plastic changes in memory encoding and non-sensory information encoding synapses during the rewarding associative learning,and shed light on the relationship between these changes and behavior and cognition.Our exploration of non-targeted lead LTP can provide insights to further understanding of the mnemonic function of hippocampus.