Electrophysiological properties of the hippocampal and medial-entorhinal circuit during spatial learning

Authors

• SO Vasu
• JH Shin
• Y Ma
• Y Gu
• VA Alvarez

Abstract

The ability to form a memory of an environment and use the memory to guide future navigation is a fundamental brain function. However, circuit mechanism underlying spatial memory formation is unclear. Previous literature demonstrates that the cognitive map of an environment is represented in the medial entorhinal cortex (MEC), a cortical area that is crucial for spatial memory and serves as a nodal point between neocortex and the hippocampus. Therefore, we hypothesized that the hippocampal fibers projecting to the MEC supports a synaptic-plasticity-based mechanism to shape the MEC cognitive map during spatial learning. To test this hypothesis, we used field and whole cell recordings to examine changes in circuit properties from the hippocampus to the MEC in mice with successful (good learners) and unsuccessful spatial learning (poor learners) in virtual environments. We electrically or optogenetically stimulated the subiculum, which mediates most projections from the hippocampus to the MEC, and recorded neural response in MEC layer 2. While the long-term potentiation of synaptic responses in the layer 2 was observed in good learners, it was absent in poor learners. Intercranial injection of channelrodopsin 2 in the subiculum showed expressions in both layers 2 and 5. When optogenetic stimulations were given to the layer 2, the excitation to inhibition balance recorded from later 2 stellate cells was specifically lower in the good learners. Overall, our findings show that under different spatial learning performances, hippocampus inputs to the MEC are differentially modulated, potentially supporting different synaptic plasticity mechanisms in the MEC.

Scientific Focus Area: Neuroscience

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