Feedback inhibition controls spike transfer in hybrid thalamic circuits

Sensory information reaches the cerebral cortex through the thalamus, which differentially relays this input depending on the state of arousal(1-5). Such 'gating' involves inhibition of the thalamocortical relay neurons by the reticular nucleus of the thalamus(6-8), but the underlying mechanisms are poorly understood. We reconstructed the thalamocortical circuit as an artificial and biological hybrid network in vitro. With visual input simulated as retinal cell activity, we show here that when the gain in the thalamic inhibitory feedback loop is greater than a critical value, the circuit tends towards oscillations-and thus imposes a temporal decorrelation of retinal cell input and thalamic relay output. This results in the functional disconnection of the cortex from the sensory drive, a feature typical of sleep states. Conversely, low gain in the feedback inhibition and the action of noradrenaline, a known modulator of arousal(4,9,10), converge to increase input-output correlation in relay neurons. Combining gain control of feedback inhibition and modulation of membrane excitability thus enables thalamic circuits to finely tune the gating of spike transmission from sensory organs to the cortex.