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The Journal of Neuroscience, March 1, 2006, 26(9):2474-2486; doi:10.1523/JNEUROSCI.3607-05.2006

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Behavioral/Systems/Cognitive
Neuronal Basis of the Slow (<1 Hz) Oscillation in Neurons of the Nucleus Reticularis Thalami In Vitro

Kate L. Blethyn, Stuart W. Hughes, Tibor I. Tóth, David W. Cope, and Vincenzo Crunelli

School of Biosciences, Cardiff University, Cardiff CF10 3US, United Kingdom

Correspondence should be addressed to S. W. Hughes, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3US, UK. Email: HughesSW{at}Cardiff.ac.uk

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 µM) or DHPG [(S)-3,5-dihydroxyphenylglycine] (100 µM) 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 Ih 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.

Key words: sleep; EEG; rhythm; thalamus; calcium current; T-type; mGluR; CAN current


Received Aug. 25, 2005; revised Jan. 13, 2006; accepted Jan. 16, 2006.

Correspondence should be addressed to S. W. Hughes, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3US, UK. Email: HughesSW{at}Cardiff.ac.uk




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