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

GOBETTO MN; WEISSMAN C; GONZÁLEZ-INCHAUSPE CARLOTA; UCHITEL OD; SALINAS C

Carlos Paz, Córdoba

Congreso; XXXIV Reunión Anual SAN 2019; 2019

Sociedad Argentina de Investigación en Neurociencias

Acid-sensing ion channels (ASICs) are H+-gated channels belonging to the ENaC/Deg superfamily that are involved in synaptic transmission and in neurodegenerative diseases. During synaptic transmission, acidification of the synaptic cleft due to the co-release of neurotransmitter and H+ from synaptic vesicles activates ASIC channels in mice. We used slices from the anterior cingulate cortex (ACC) of P30-60 postnatal mice to evoke glutamatergic AMPA receptor-mediated excitatory postsynaptic currents (EPSCs), recorded in whole-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 neuromodulator histamine, which specifically modulates homomeric ASIC-1a channels, as well as by corticosterone. Long-term potentiation (LTP) is a major type of long-lasting synaptic plasticity and is associated with learning, memory, development and neuropathic pain. Neurons in the ACC play critical roles in chronic pain. LTP was induced by theta burst stimulation (TBS) of the callosal afferents. Extracellular field EPSP and whole-cell patch-clamped EPSC recordings demonstrated that ASIC-SCs contribute to ACC LTP induction. Stimulated by a TBS below threshold, glutamatergic synapses undergo LTP by the potentiating effect of histamine on ASIC channels, which is prevented by previous incubation with psalmotoxin-1.