Associative Learning-Induced Synaptic Potentiation at the Two Major Hippocampal CA1 Inputs for Cued Memory Acquisition

 Bing‑Ying Wang1  · Bo Wang1  · Bo Cao1  · Ling‑Ling Gu1  · Jiayu Chen1  · Hua He3  · Zheng Zhao1  · Fujun Chen2  · Zhiru Wang1
1 Institute and Key Laboratory of Brain Functional Genomics of Chinese Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai 200062, China 
2 Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200030, China 
3 Department of Neurosurgery, Third Afliated Hospital of Navy Military Medical University, Shanghai 200438, China

Abstract
Learning-associated functional plasticity at hippocampal synapses remains largely unexplored. Here, in a single session of reward-based trace conditioning, we examine learning-induced synaptic plasticity in the dorsal CA1 hippocampus (dCA1). Local field-potential recording combined with selective optogenetic inhibition first revealed an increase of dCA1 synaptic responses to the conditioned stimulus (CS) induced during conditioning at both Schaffer collaterals to the stratum radiatum (Rad) and temporoammonic input to the lacunosum moleculare (LMol). At these dCA1 inputs, synaptic potentiation of CS-responding excitatory synapses was further demonstrated by locally blocking NMDA receptors during conditioning and whole-cell recording sensory-evoked synaptic responses in dCA1 neurons from naive animals. An overall similar time course of the induction of synaptic potentiation was found in the Rad and LMol by multiple-site recording; this emerged later and saturated earlier than conditioned behavioral responses. Our experiments demonstrate a cued memory-associated dCA1 synaptic plasticity induced at both Schaffer collaterals and temporoammonic pathways.

Keywords
Hippocampus; Synaptic plasticity; Long-term potentiation; Associative learning; Trace conditioning; Schafer collateral; Temporoammonic