Subcellular Localization and Activity of TRPM4 in Medial Prefrontal Cortex Layer 2/3

TRPM4 is a Ca2+-activated non-selective cationic channel that conducts monovalent cations. TRPM4 has been proposed to contribute to burst firing and sustained activity in several brain regions, however, the cellular and subcellular pattern of TRPM4 expression in medial prefrontal cortex (mPFC) during postnatal development has not been elucidated. Here, we use multiplex immunofluorescence labeling of brain sections to characterize the postnatal developmental expression of TRPM4 in the mouse mPFC. We also performed electrophysiological recordings to correlate the expression of TRPM4 immunoreactivity with the presence of TRPM4-like currents. We found that TRPM4 is expressed from the first postnatal day, with expression increasing up to postnatal day 35. Additionally, in perforated patch clamp experiments, we found that TRPM4like currents were active at resting membrane potentials at all postnatal ages studied. Moreover, TRPM4 is expressed in both pyramidal neurons and interneurons. TRPM4 expression is localized in the soma and proximal dendrites, but not in the axon initial segment of pyramidal neurons. This subcellular localization is consistent with a reduction in the basal current only when we locally perfused 9-Phenanthrol in the soma, but not upon perfusion in the medial or distal dendrites. Our results show a specific localization of TRPM4 expression in neurons in the mPFC and that a 9-Phenanthrol sensitive current is active at resting membrane potential, suggesting specific functional roles in mPFC neurons during postnatal development and in adulthood.Fondecyt Fondo Nacional de Desarrollo Cientifico y Tecnologico 11140731 1141132 1160518 Programa de Atraccion e Insercion de Capital Humano Avanzado (PAI) Comision Nacional de Investigacion Cientifica y Tecnologica 79140059 Comision Nacional de Investigacion Cientifica y Tecnologica Financiamiento Basal para Centros Cientificos y Tecnologicos de Excelencia FB 0807 National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) R01 NS042225 Iniciativa Cientifica Milenio of the Ministry of Economy, Development and Tourism (Chile