THE KCNQ4 SUBUNIT MEDIATED M-CURRENT OF THE PEDUNCULOPONTINE NUCLEUS –AN UPDATE
Balazs Pal1, Tsogbadrakh Bayasgalan1, Guillermo Spitzmaul2, 3, Sofia Stupniki2-3, Leonardo Dionisio2, 3, Gabriel T. Perotti3, Leandro Dye2-3, Adrienn Kovács1
The pedunculopontine nucleus (PPN) is known as a cholinergic member of the reticular activating system (RAS). Synchronization of the PPN neurons was observed in parallel with cortical slow wave activity, whereas loss of synchronization is seen during desynchronized cortical states. A potential synchronizer of the cholinergic neurons is the M-current, which is a slowly activating, non-inactivating voltage-gated potassium current that can be mediated by KCNQ2 to -5 channel subunits. We previously determined that the M-current is a hallmark of the cholinergic neurons. We also showed that, based on functional data, this current is partially mediated by KCNQ4 subunit and capable of synchronizing neighboring cholinergic neurons. Together with an update of our previous electrophysiological findings, we provide further evidence of the existence of KCNQ4 subunit in the PPN with molecular and behavioral studies. We analyzed KCNQ4 expression by qPCR and its localization using immunofluorescence on brain preparations. Our results showed a weak mRNA-expression of KCNQ4 in the region of the PPN. In agreement with this, KCNQ4 immunoreactivity was present only on a small subpopulation of cholinergic neurons located laterally in the PPN. We also found that KCNQ4 knockout mice have alterations of the circadian rhytm compared to wild type littermates. In summary, we provided further support to our previous functional findings that KCNQ4 subunit mediated M-current significantly affects the PPN cholinergic neurons. As this subunit is selectively expressed in the RAS and the auditory brainstem, it might serve as a pharmacological target for modulating sleep-wakefulness cycles. Supported by TÉT_15-1-2016-0087 (BP) and MECCyT-NRDIO HU/17/02 (BP and GS).