Thalamocortical mechanisms for a propofol-induced alpha rhythm
Monday, Nov 15, 2010, 10:00 AM -11:00 AM
, A. CIMENSER
, P. L. PURDON
, E. N. BROWN
, N. J. KOPELL
Anesthesia and Critical Care, Massachusetts Gen. Hosp., Boston, MA;
Mathematics and Statistics, Boston Univ., Boston, MA;
Brain and Cognitive Sci., MIT, Cambridge, MA;
Harvard Med. Sch., Boston, MA
The anesthetic agent propofol is known to elicit frontal alpha (10-13Hz) rhythms in the electroencephalogram (Feshchenko et. al., Neuropsychobiology. 50(3):257-66). New data suggest that this rhythm, which is spatially distinct from the classical occipital alpha rhythm, is highly coherent across electrodes. Moreover, its appearance is well-correlated with anesthetic-induced loss of consciousness. Although much is known about the molecular actions of propofol, an understanding of the network mechanisms that lead to such EEG-level phenomena remains absent. The present work uses computational models in an attempt to elucidate some of these mechanisms. It builds on (McCarthy et. al., J. Neurosci. 28(50):13488-13504), in which a cortical model was used to reveal network changes that may underlie the paradoxical excitation associated with low doses of propofol. Here, these mechanisms are incorporated into a broader thalamocortical model that accounts for the aforementioned EEG changes associated with the administration of higher, anesthetic doses.
Specifically, the model suggests that propofol enhances the projections from cortex to thalamus, resulting in a well-coordinated thalamocortical alpha oscillation. We consider a network of cortical pyramidal cells (PY) and interneurons (IN), coupled with thalamocortical (TC) and thalamic reticular (RE) neurons. Reciprocal projections between the PY and TC cells form an excitatory thalamocortical loop. Propofol enters the model through the dynamics of GABAa inhibitory synapses. At low levels of the drug, the cortical part of the model produces the expected paradoxical excitation while the thalamic part fires at a slower, irregular rate. Potentiating GABAa conductance and decay time to a level commensurate with a higher dose of the drug causes cortical cell firing to slow into the alpha range. Importantly, this also changes the thalamic substrate by increasing the inhibition delivered by the RE to the TC, producing rebound spiking. Thus, the cortical input to the thalamus is effectively enhanced, enabling the latter to be recruited into the same alpha frequency. Since the reticular nucleus innervates widely, it is likely to synchronize thalamic oscillations. These oscillations then manifest coherently at the cortex through the thalamocortical loop. In contrast to the notion of a thalamic ‘off-switch,’ this model suggests that the thalamus is engaged in rhythmic activity at deep levels of general anesthesia. Such a rhythm may limit the efficacy of the thalamus in propagating specific signals upward, thus promoting loss of consciousness.
NIH Grant DP1 OD003646
[Authors]. [Abstract Title]. Program No. XXX.XX. 2010 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2010. Online.
2010 Copyright by the Society for Neuroscience all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.
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