ACTIVITY-DEPENDENT MODULATION OF THALAMIC INHIBITION BY TREK-1 CHANNELS AND ADENOSINE RECEPTORS

Precise regulation of inhibitory synaptic transmission in the thalamocortical (TC) circuit is essential for sensory processing and network dynamics. Both intrinsic ion channels and neuromodulatory compounds shape GABAergic input from reticular thalamic nucleus (RTN) neurons onto ventrobasal (VB) TC neurons, yet their interplay remains poorly understood. Here, we investigated how TREK-1 potassium channels and adenosine receptors (A₁, A_2A) influence inhibitory GABAergic tone within the somatosensory TC circuit. Miniature and evoked inhibitory postsynaptic currents (mIPSCs and eIPSCs) were recorded from VB TC neurons while pharmacological modulation of adenosine receptors and TREK-1 channels was exerted. TREK-1 genetic deletion did not affect mIPSC amplitude, frequency, or kinetics, indicating preserved spontaneous GABA release, but increased the paired-pulse ratio (PPR) of eIPSCs, consistent with reduced presynaptic release probability. Acute pharmacological blockade of TREK-1 failed to reproduce its genetic deletion effect; instead, it selectively altered IPSC decay kinetics without affecting PPR, highlighting mechanistic differences between chronic and acute loss of channel function. Similarly, adenosine receptor antagonists did not alter mIPSCs, but an activity-dependent modulation was found during repetitive stimulations with indications for the involvement of pre- and postsynaptic mechanisms. Together, these results indicate that TREK-1 channels set a basal presynaptic constraint on GABA release, while adenosine receptors dynamically tune inhibitory transmission in a frequency- and compartment-specific manner.