Rebound depolarization (RD) in medial prefrontal cortex (mPFC) pyramidal neurons
INTRODUCTION: Rebound depolarization (RD) is an evoked membrane depolarization following the hyperpolarization of a neuron that converts an arriving inhibitory signal into cell excitation, which is subsequently transmitted to other neurons. RD is involved in the rhythmic discharges and oscillations of cortical neurons. AIM(S): The aim of this study was to clarify the intrinsic mechanism responsible for RD in medial prefrontal cortex (mPFC) pyramidal neurons. METHOD(S): Experiments were performed on layer V mPFC pyramidal neurons in slices obtained from 60-day-old rats. Recordings of membrane potential were performed in whole‑cell current‑clamp configuration in the absence of Ca2+ ions and in the presence of tetrodotoxin (TTX), glutamatergic and GABAergic blockers in extracellular solution. RESULTS: The resting membrane potential in tested neurons was −67.3±0.95 mV (n=154). RD exhibited the following properties: evoked after prior cell hyperpolarization below −80 mV, a threshold of −63.8±1.3 mV, an amplitude of 33.2±1.7 mV above the resting membrane potential, a duration of 552.7±43.1 ms, and dependence on inward TTX-resistant Na+ current. RD was abolished when pyramidal neurons were treated with Nav1.9 antibodies. RD was only evoked in the absence of Ca2+ in the extracellular solution or in the presence of Ca2+ together with a BK-type Ca2+-dependent K+ channel current blocker (paxilline, 10 µM) in the extracellular solution. CONCLUSIONS: The obtained results suggest that hyperpolarization-dependent RD in layer V mPFC pyramidal neurons is evoked by the de-inactivation and subsequent activation of a voltage-dependent, low-threshold and TTX-resistant, inward Nav1.9-like Na+ current. In the presence of Ca2+ ions in the extracellular solution, RD was suppressed due to the activation of BK channel currents. FINANCIAL SUPPORT: The study was supported by National Science Centre (Poland) grant no: 2015/17/N/ NZ4/02889.