Substance P induces plasticity and synaptic tagging/capture in rat hippocampal area CA2

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Abstract

The hippocampal area Cornu Ammonis (CA) CA2 is important for social interaction and is innervated by Substance P (SP)-expressing supramammillary (SuM) nucleus neurons. SP exerts neuromodulatory effects on pain processing and central synaptic transmission. Here we provide evidence that SP can induce a slowly developing NMDA receptor- and protein synthesis-dependent potentiation of synaptic transmission that can be induced not only at entorhinal cortical (EC)-CA2 synapses but also at long-term potentiation (LTP)resistant Schaffer collateral (SC)-CA2 synapses. In addition, SP-induced potentiation of SC-CA2 synapses transforms a short-term potentiation of EC-CA2 synaptic transmission into LTP, consistent with the synaptic tagging and capture hypothesis. Interestingly, this SP-induced potentiation and associative interaction between the EC and SC inputs of CA2 neurons is independent of the GABAergic system. In addition, CaMKIV and PKMζ play a critical role in the SP-induced effects on SC-CA2 and EC-CA2 synapses. Thus, afferents from SuM neurons are ideally situated to prime CA2 synapses for the formation of long-lasting plasticity and associativity.

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Dasgupta, A., Baby, N., Krishna, K., Hakim, M., Wong, Y. P., Behnisch, T., … Sajikumar, S. (2017). Substance P induces plasticity and synaptic tagging/capture in rat hippocampal area CA2. Proceedings of the National Academy of Sciences of the United States of America, 114(41), E8741–E8749. https://doi.org/10.1073/pnas.1711267114

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