Histamine significantly increases ASIC-1a contribution to excitatory synaptic transmission at the calyx of Held

C. GONZÁLEZ INCHAUSPE; OSVALDO D. UCHITEL

San Diego, California

Congreso; Annual Meeting of Society for Neuroscience; 2018

Society for Neuroscience

Session:Poster: 648 - Synaptic Transmission: Modulation: Mechanisms of Action Acid-sensingion channels (ASICs) regulate synaptic activities and play important roles inneurodegenerative diseases. We found that homomeric ASIC-1a channels areexpressed in neurons of the medial nucleus of the trapezoid body (MNTB) of theauditory system in the CNS. During synaptic transmission, acidification of thesynaptic cleft, presumably due to the co-release of neurotransmitter and H+from synaptic vesicles, activates postsynaptic ASIC-1a channels, generatingsynaptic currents (ASIC-SCs) that add to the glutamatergic excitatorypostsynaptic currents (EPSCs). Here we report that neuromodulators likehistamine (0.1-1mM) potentiate ASIC-SCs up to 84 ± 4 % and that naturalproducts like lactate and spermine potentiate ASIC-SCs in an additive form upto 221 ± 18 %, such that excitatory ASIC synaptic currents as well as theassociated calcium influx became significantly large and physiologicallyrelevant. We show that potentiated ASIC currents by endogenous neuromodulatorsare capable of supporting synaptic transmission in the absence of glutamatergicEPSC. Furthermore, at high frequency stimulation, ASIC-SCs contribute todiminish short term depression (STD) and their contribution is even morerelevant at early stages of development. Since ASIC channels are present inalmost all type of neurons and synaptic vesicles content is acid, theparticipation of protons in synaptic transmission and its enhancement byendogenous substance could be a general phenomenon across the central nervoussystem.