Neuronal basis of the slow (<1 Hz) oscillation in neurons of the nucleus reticularis thalami in vitro

During deep sleep and anesthesia, the EEG of humans and animals exhibits a distinctive slow ( < 1 Hz) rhythm. In inhibitory neurons of the nucleus reticularis thalami (NRT), this rhythm is reflected as a slow ( < 1 Hz) oscillation of the membrane potential comprising stereotypical, recurring "up" and "down" states. Here we show that reducing the leak current through the activation of group I metabotropic glutamate receptors (mGluRs) with either trans-ACPD[(+/-)-1-aminocyclopentane- trans-1,3-dicarboxylic acid] ( 50 - 100 mu M) or DHPG [( S)- 3,5-dihydroxyphenylglycine] ( 100 mu M) instates an intrinsic slow oscillation in NRT neurons in vitro that is qualitatively equivalent to that observed in vivo. A slow oscillation could also be evoked by synaptically activating mGluRs on NRT neurons via the tetanic stimulation of corticothalamic fibers. Through a combination of experiments and computational modeling we show that the up state of the slow oscillation is predominantly generated by the "window" component of the T-type Ca2+ current, with an additional supportive role for a Ca2+-activated nonselective cation current. The slow oscillation is also fundamentally reliant on an I-h current and is extensively shaped by both Ca2+- and Na+- activated K+ currents. In combination with previous work in thalamocortical neurons, this study suggests that the thalamus plays an important and active role in shaping the slow ( < 1 Hz) rhythm during deep sleep.