In relaxed wakefulness, the EEG exhibits robust rhythms in the alpha band (8-13 Hz), which decelerate to theta (approximately 2-7 Hz) frequencies during early sleep. In animal models, these rhythms occur coherently with synchronized activity in the thalamus. However, the mechanisms of this thalamic activity are unknown. Here we show that, in slices of the lateral geniculate nucleus maintained in vitro, activation of the metabotropic glutamate receptor (mGluR) mGluR1a induces synchronized oscillations at alpha and theta frequencies that share similarities with thalamic alpha and theta rhythms recorded in vivo. These in vitro oscillations are driven by an unusual form of burst firing that is present in a subset of thalamocortical neurons and are synchronized by gap junctions. We propose that mGluR1a-induced oscillations are a potential mechanism whereby the thalamus promotes EEG alpha and theta rhythms in the intact brain.

The slow (<1 Hz) rhythm is a defining feature of the electroencephalogram during sleep. Since cortical circuits can generate this rhythm in isolation, it is assumed that the accompanying slow oscillation in thalamocortical (TC) neurons is largely a passive reflection of neocortical activity. Here we show, however, that by activating the metabotropic glutamate receptor (mGluR), mGluR1a, cortical inputs can recruit intricate cellular mechanisms that enable the generation of an intrinsic slow oscillation in TC neurons in vitro with identical properties to those observed in vivo. These mechanisms rely on the "window" component of the T-type Ca(2+) current and a Ca(2+)-activated, nonselective cation current. These results suggest an active role for the thalamus in shaping the slow (<1 Hz) sleep rhythm.

European Society of Anaesthesiology.

During deep sleep and anesthesia, the EEG of humans and animals exhibits a distinctive slow (Ͻ1 Hz) rhythm. In inhibitory neurons of the nucleus reticularis thalami (NRT), this rhythm is reflected as a slow (Ͻ1 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 [(ϩ/Ϫ)-1-aminocyclopentane-trans-1,3-dicarboxylic acid] (50 -100 M) or DHPG [(S)-3,5-dihydroxyphenylglycine] (100 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 Ca 2ϩ current, with an additional supportive role for a Ca 2ϩ -activated nonselective cation current. The slow oscillation is also fundamentally reliant on an I h current and is extensively shaped by both Ca 2ϩ -and Na ϩ -activated K ϩ 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 (Ͻ1 Hz) rhythm during deep sleep.

All three forms of recombinant low voltage-activated T-type Ca2+ channels (Ca v 3.1, Ca v 3.2 and Ca v 3.3) exhibit a small, though clearly evident, window T-type Ca 2+ current (I Twindow ) which is also present in native channels from different neuronal types. In thalamocortical (TC) and nucleus reticularis thalami (NRT) neurones, and possibly in neocortical cells, an I Twindow -mediated bistability is the key cellular mechanism underlying the expression of the slow (< 1 Hz) sleep oscillation, one of the fundamental EEG rhythms of non-REM sleep. As the I Twindow -mediated bistability may also represent one of the cellular mechanisms underlying the expression of high frequency burst firing in awake conditions, I Twindow is of critical importance in neuronal population dynamics associated with different behavioural states.