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The Involvement of PACAP/VIP System in the Synaptic Transmission in the Hippocampus

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Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two closely related peptides, which can activate protein kinase A (PKA). At least three receptors for PACAP and VIP have been identified. The PACAP-specific receptor, PAC1 receptor, exhibits a higher affinity for PACAP than VIP, whereas VIP receptors, VPAC1-R and VPAC2-R, have similar affinities for PACAP and VIP. Both PACAP/VIP and their cognate receptors are highly expressed in the brain, including the hippocampus. Recently, their roles in the regulation of synaptic transmission have begun to emerge. PACAP/VIP can signal through different pathways to regulate N-methyl-d-aspartate (NMDA) receptors in CA1 pyramidal cells. The activation of VPAC1/2-Rs increases evoked NMDA currents via the cyclic AMP/PKA pathway. However, the activation of PAC1-R stimulates a PLC/PKC/Pyk2/Src signaling pathway to enhance NMDA receptor function in hippocampal neurons. Furthermore, different concentrations of PACAP induce different effects on the both α-amino-3-hydroxy-5-isoxazole-propionic acid-evoked current and basal synaptic transmission by activating different receptors. Their roles in learning and memory are also demonstrated using transgenic mice and pharmacological methods.

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Authors and Affiliations

  1. Department of Physiology, University of Toronto, I King’s College Circle, Toronto, ON, Canada, M5S 1A8

    Kai Yang & John F. MacDonald

  2. Robarts Research Institute, Molecular Brain Research Group, University of Western Ontario, 100 Perth Drive, London, ON, Canada, N6A 5K8

    Gang Lei, Michael F. Jackson & John F. MacDonald

  3. Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada, N6A 5K8

    Michael F. Jackson & John F. MacDonald

  4. Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada, N6A 5K8

    John F. MacDonald

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  1. Kai Yang
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  2. Gang Lei
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  3. Michael F. Jackson
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  4. John F. MacDonald
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Correspondence to John F. MacDonald.

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This work was supported by grants to JFM from the Canadian Institutes of Health Research (15514 and 44008).

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Yang, K., Lei, G., Jackson, M.F. et al. The Involvement of PACAP/VIP System in the Synaptic Transmission in the Hippocampus. J Mol Neurosci 42, 319–326 (2010). https://doi.org/10.1007/s12031-010-9372-7

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  • DOI: https://doi.org/10.1007/s12031-010-9372-7

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