Proposed thalamocortical circuits dynamics. Two thalamocortical systems are shown. The specific pathway (yellow, left of each panel) activates layer IV pyramidal cells (blue) and inhibitory interneurons (red) producing cortical oscillations by direct activation and feed-forward inhibition. Collaterals of this projection produce thalamic feedback inhibition through the reticular nucleus (red at thalamic level). The return cortico-thalamic pathway (circular arrow on the left) from layer V and VI pyramidal cells (blue) reenters this oscillatory loop to specific and reticular thalamic nuclei. The nonspecific thalamocortical pathway (green, right of each panel) projects to the most superficial layer of the cortex and gives collaterals to the reticular nucleus. Layer V and VI pyramidal cells (blue) return the oscillation to the nonspecific and reticular thalamic nuclei, establishing a second resonant loop (circular arrow on the right). The conjunction of the specific and nonspecific loops is proposed to generate temporal coherence. During thalamo-cortical dysrhythmia, protracted hyperpolarization of thalamic cells increases low-frequency neuronal oscillations. Either disfacilitation, as occurs after deafferentation or excess inhibition caused by pallidal over-activity (as in Parkinsons disease), hyperpolarizes the cells sufficiently to deinactivate T-type calcium channels and increase thalamic oscillations at theta (4–8 Hz) range. Such oscillations can entrain thalamocortical loops and generate increased coherence in affected brain regions (left). At the cortical level, low-frequency activation of intracortical inhibitory neurons (middle red arrow) can reduce lateral inhibitory drive and result in high-frequency, phase-locked coherent activation of neighboring cortical modules, described here as the edge effect (right) (modified from Llinás et al. 2005).