Characterizing the responsiveness of thalamic neurons is crucial to understanding the flow of sensory information. Typically, thalamocortical neurons possess two distinct firing modes. At depolarized membrane potentials, thalamic cells fire single action potentials and faithfully relay synaptic inputs to the cortex. At hyperpolarized potentials, the activation of T-type calcium channels promotes burst firing, and the transfer is less accurate. Our results suggest that this duality no longer holds if synaptic background activity is taken into account. By injecting stochastic conductances into guinea-pig thalamocortical neurons in slices, we show that the transfer function of these neurons is strongly influenced by conductance noise. The combination of synaptic noise with intrinsic properties gives a global responsiveness that is more linear, mixing single-spike and burst responses at all membrane potentials. Because in thalamic neurons, background synaptic input originates mainly from cortex, these results support a determinant role of corticothalamic feedback during sensory information processing.

Sensory information reaches the cerebral cortex through the thalamus, which differentially relays this input depending on the state of arousal. Such 'gating' involves inhibition of the thalamocortical relay neurons by the reticular nucleus of the thalamus, 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, 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.

Thalamic circuits have an intrinsic capacity to generate state-dependent oscillations of different frequency and degrees of synchrony, but little is known of how synchronized oscillation is controlled in the intact brain or what function it may serve. The influence of cortical feedback was examined using slice preparations of the visual thalamus and computational models. Cortical feedback was mimicked by stimulating corticothalamic axons, triggered by the activity of relay neurons. This artificially coupled network had the capacity to self-organize and to generate qualitatively different rhythmical activities according to the strength of corticothalamic feedback stimuli. Weak feedback (one to three shocks at 100-150 Hz) phase-locked the spontaneous spindle oscillations (6-10 Hz) in geniculate and perigeniculate nuclei. However, strong feedback (four to eight shocks at 100-150 Hz) led to a more synchronized oscillation, slower in frequency (2-4 Hz) and dependent on GABA(B) receptors. This increase in synchrony was essentially attributable to a redistribution of the timing of action potential generation in lateral geniculate nucleus cells, resulting in an increased output of relay cells toward the cortex. Corticothalamic feedback is thus capable of inducing highly synchronous slow oscillations in physiologically intact thalamic circuits. This modulation may have implications for a better understanding of the descending control of thalamic nuclei by the cortex, and the genesis of pathological rhythmical activity, such as absence seizures.

No abstract