TREK1 Channels Shape Spindle-Like Oscillations, Neuronal Activity, and Short-Term Synaptic Plasticity in Thalamocortical Circuits.

Labbaf A; Krauth V; Rychlik N; Narayanan Naik V; Vinnenberg L; Karabatak E; Teasley A; Perissinotti PP; White JA; Meuth SG; van Luijtelaar G; Urbano FJ; Budde T; Zobeiri M

Zusammenfassung

Although TREK1 channels are widely expressed in several thalamic nuclei, the role of this K2P family member in modulating thalamic cell excitability and physiological thalamocortical oscillatory activity is not well studied. Here we explored the contribution of TREK1 channels to membrane properties of two important building blocks of the thalamocortical (TC) system, namely, GABAergic neurons of reticular thalamic nucleus (RTN) and TC neurons in different sensory thalamic nuclei including the ventrobasal complex (VB; somatosensory system) and the medial geniculate nucleus (MGN; auditory system), using male TREK1 knock-out (TREK1-/-) mice. Furthermore, we show that the loss of TREK1 channels has distinct effects on neuronal function in different thalamic nuclei. Compared with controls, TREK1-/- mice exhibit decreased excitability in RTN neurons, while VB neurons maintain similar excitability levels. Additionally, the absence of TREK1 channels alters the action potential (AP) characteristics in VB TC neurons and affects GABAergic inhibitory tone in RTN neurons. In TREK1-/- mice, the excitability of cortical pyramidal cells is increased. It is tempting to assume that this combination of changes contributes to a high number of sharp, spindle-like oscillations observed in sleep local field potential (LFP) recordings of these mice. In addition, TREK1-/- mice show a lower amount of delta (1-4 Hz) oscillations during slow-wave sleep and a time-of-day-dependent alteration in the amount of sleep and wakefulness. They also show disturbed auditory signal processing and altered excitability in the auditory thalamus. These findings underline the relevance of TREK1 channels' broad contribution to the thalamus and thalamocortical system.