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Publication : NMDAR-mediated activation of pannexin1 channels contributes to the detonator properties of hippocampal mossy fiber synapses.

First Author  Rangel-Sandoval C Year  2024
Journal  iScience Volume  27
Issue  5 Pages  109681
PubMed ID  38680664 Mgi Jnum  J:347880
Mgi Id  MGI:7625913 Doi  10.1016/j.isci.2024.109681
Citation  Rangel-Sandoval C, et al. (2024) NMDAR-mediated activation of pannexin1 channels contributes to the detonator properties of hippocampal mossy fiber synapses. iScience 27(5):109681
abstractText  Pannexins are large-pore ion channels expressed throughout the mammalian brain that participate in various neuropathologies; however, their physiological roles remain obscure. Here, we report that pannexin1 channels (Panx1) can be synaptically activated under physiological recording conditions in rodent acute hippocampal slices. Specifically, NMDA receptor (NMDAR)-mediated responses at the mossy fiber to CA3 pyramidal cell synapse were followed by a slow postsynaptic inward current that could activate CA3 pyramidal cells but was absent in Panx1 knockout mice. Immunoelectron microscopy revealed that Panx1 was localized near the postsynaptic density. Further, Panx1-mediated currents were potentiated by metabotropic receptors and bidirectionally modulated by burst-timing-dependent plasticity of NMDAR-mediated transmission. Lastly, Panx1 channels were preferentially recruited when NMDAR activation enters a supralinear regime, resulting in temporally delayed burst-firing. Thus, Panx1 can contribute to synaptic amplification and broadening the temporal associativity window for co-activated pyramidal cells, thereby supporting the auto-associative functions of the CA3 region.
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