TRPM4 conductances in thalamic reticular nucleus neurons generate persistent firing during slow oscillations

During slow-wave sleep (SWS) and anesthesia, thalamocortical networks generate slow (< 1 Hz) oscillations, with activity in individual neurons showing rhythmic fluctuations between Up and Down States. Neocortical Up states are driven by persistent synaptic activity in recurrent networks. In contrast, rhythmic up states in thalamic neurons are thought to be primarily mediated by cell-intrinsic mechanisms, with postsynaptic Group 1 metabotropic glutamate receptor (mGluR) activation leading to the generation of long-lasting plateau potentials mediated by both T-type Ca2+ currents and calcium-activated nonselective cation currents (ICAN). However, the molecular identity of ICAN and the role of thalamic synaptic networks in generating slow oscillations remain unclear. By performing recordings in thalamic slices derived from adult mice of either sex, we observed robust slow oscillatory network activity that did not require mGluR signaling but was completely eliminated in the absence of fast glutamatergic signaling. We found that thalamic glutamatergic inputs triggered persistent firing (PF) in neurons of the thalamic reticular nucleus (TRN). For about 30% of TRN neurons, PF could also be evoked by brief depolarizing steps, while the remaining neurons displayed burst firing. PF was driven by long-lasting plateau potentials that were triggered by Ca2+ influx through T-type Ca2+ channels and mediated by Ca2+ and voltage-dependent transient receptor potential melastatin 4 (TRPM4) channels. Taken together, our results suggest that slow oscillatory activity in TRN neurons typical for SWS is mediated by cell-intrinsic mechanisms that generate PF, and synaptic networks interconnecting TRN with thalamic relay nuclei that generate rhythmicity.