It is well established that thalamus plays a crucial role in the generation of the synchronous slow oscillation in the cortex during non-REM sleep. The slow/delta power (0.2–4 Hz) is the main measured factor of the quality of sleep. However, the contribution of different thalamic nuclei to the inception of the slow wave activities and its synchronization is not known. We hypothesized that the first-order (specific) thalamic nuclei provide a control of slow waves in primary cortical areas, while higher-order (non-specific) thalamic nuclei may synchronize the slow-wave activities across wide cortical regions. We analyzed local field potentials and spiking activities from different cortical and thalamic areas of anesthetized mice while a thalamic nucleus was inactivated by the GABA-agonist muscimol. Extracellular multiunit recordings in first-order (VPM, VL) and higher-order (PO, CL) thalamic nuclei show dramatically decreased spiking activity and strongly reduced burst firing after inactivation. We conclude that the injection of muscimol strongly reduced the spiking activity and does not potentiate the generation of low-threshold spike mediated bursts. Inactivation of specific thalamic nuclei with muscimol decreased the slow/delta power in the corresponding primary cortical area. The inactivation of a non-specific nucleus with muscimol significantly reduced the delta power in all investigated cortical. Our experiments demonstrate that the thalamus is required for the fine tuning of the cortical slow oscillation. Supported by CIHR and NSERC.