Although it is well established that low-voltage activated T-type Ca2+ channels play a key role in many neurophysiological functions and pathological states, the lack of selective and potent antagonists has so far hampered a detailed analysis of the full impact that these channels might have on single cell and neuronal network excitability as well as on calcium homeostasis. Using thalamic slices (prepared from fully anaesthetized Wistar rats or transgenic mice, in accordance with the UK Scietific Procedure Act), we now show that the novel piperidine-based molecule TTA-P2 exerts a specific, potent (IC50: 22nM) and reversible inhibition of T-type Ca2+ currents (IT) in both thalamocortical (TC) and reticular thalamic nucleus (NRT) neurons without any action on HVA Ca2+ currents. Under current clamp conditions, 1µM TTA-P2, a concentration that fully blocks IT (96±1%, n=7), has no effect on tonic firing and action potential characteristics (threshold, half-width, amplitude, afterhyperpolarization), but abolishes the low threshold Ca2+ potential (LTCP)-dependent high frequency burst firing of thalamic neurons. In addition, when TC and NRT neurons are held at -60mV, application of 1µM TTA-P2 produces a tonic hyperpolarization of 3.1±0.5mV (n=11) and 5±2.2mV (n=6), respectively. Such hyperpolarization is not observed when TC neurons are held at -70mV or in TC neurons from Cav3.1 KO mice that are recorded at -60mV (n=6). These data demonstrate that the TTA-P2 induced hyperpolarization is due to the block of the window component of IT and that this current contributes to the resting membrane potential of thalamic neurons. In addition, we could show that application of 1µM TTA-P2 blocks membrane potential bistability of TC neurons in slices that are perfused with the h-channel blocker ZD 7288 (100µM) (n=4). Thus, the use of TTA-P2 has allowed to consolidate and enlarge our current understanding of the contribution of IT to single TC neuron excitability, and to provide the first direct demonstration that the window component of IT underlies the intrinsically generated slow (<1Hz) sleep oscillation of thalamic neurons.