Alteration of mesopontine cholinergic function by the lack of KCNQ4 subunit

BAYASGALAN, T.; STUPNIKI, S.; KOVÁCS, A.; CSEMER, A.; SZENTESI, P.; POCSAI, K.; DIONISIO, L.; SPITZMAUL, G. (AUTOR CORRESPONDIENTE); PAL, B.

Frontiers in Cellular Neuroscience

Frontiers Research Foundation

Lugar: Lausanne; Año: 2021

The pedunculopontine nucleus (PPN), a structure known as a cholinergic member of the reticular activating system (RAS), is source and target of cholinergic neuromodulation and contributes to regulation of sleep-wakefulness cycles. The M-current is a voltage-gated potassium current modulated mainly by cholinergic signaling. KCNQ subunits ensemble into ion channels responsible for the M-current. In the central nervous system (CNS), KCNQ4 expression is restricted to certain brainstem structures as RAS nuclei. Here, we investigated the presence and functional significance of KCNQ4 in the PPN by behavioral studies, as well as gene and protein expression and slice electrophysiology using a mouse model lacking KCNQ4 expression. We found that this mouse has alterations in the adaptation to changes in light-darkness (LD) cycles, representing the potential role of KCNQ4 in the regulation of sleep-wakefulness cycles. As cholinergic neurons from the PPN participate in the regulation of this cycle, we investigated whether the cholinergic PPN might also possess functional KCNQ4 subunits. Although the M-current is an electrophysiological hallmark of the cholinergic neurons, only a subpopulation of them had KCNQ4-dependent M-current. Interestingly, the absence of KCNQ4 subunit altered the expression pattern of other KCNQ subunits in the PPN. We also determined that in WT animals, the cholinergic inputs of the PPN modulated the M-current and these in turn can modulate the level of synchronization between neighboring PPN neurons. Taken together, the KCNQ4 subunit is present in a subpopulation of PPN cholinergic neurons and it may contribute to regulation of sleep-wakefulness cycles.