Histamine-enhanced ASIC mediated currents contribute to anterior cingulate cortex long-term potentiation.

CARLOTA GONZALEZ INCHAUSPE; OSVALDO DANIEL UCHITEL; LIBIA CATALINA SALINAS; MARÍA NATALIA GOBETTO; CARINA WEISSMAN

Buenos Aires

Congreso; XXXIV Reunión Anual de la Sociedad Argentina de Investigación en Neurociencia (SAN); 2019

Sociedad Argentina de Investigación en Neurociencia (SAN)

Acid-sensingion channels (ASICs) are H+-gated channels belonging to the ENaC/Deg superfamily that are involvedin synaptic transmission and in neurodegenerative diseases. During synaptictransmission, acidification of the synaptic cleft due to the co-release ofneurotransmitter and H+ from synaptic vesicles activates ASIC channels in mice. We used slicesfrom the anterior cingulate cortex (ACC) of P30-60 mice to evoke glutamatergicAMPA receptor-mediated excitatory postsynaptic currents (EPSCs), recorded inwhole-cell patch-clamp at layer I pyramidal neurons. After blocking AMPA, NMDA,GABA and glycine receptors, we detected ASIC mediated synaptic currents(ASIC-SCs) sensitive to ASIC-1a inhibitor psalmotoxin-1.  ASIC-SCs were enhanced by the neuromodulatorhistamine, which specifically modulates homomeric ASIC-1a channels, as well asby corticosterone. Long-termpotentiation (LTP) is a major type of long-lasting synaptic plasticity and isassociated with learning, memory, development and neuropathic pain. Neurons inthe ACC play critical roles in chronic pain. LTP was induced by theta burststimulation (TBS) of the callosal afferents. Extracellular field EPSP andwhole-cell patch-clamped EPSC recordings demonstrated that ASIC-SCs contributeto ACC LTP induction. Stimulated by a TBS below threshold, glutamatergic synapsesundergo LTP by the potentiating effect of histamine on ASIC channels, which isprevented by previous incubation with psalmotoxin-1.