QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, December 10, 2008, 28(50):13488-13504; doi:10.1523/JNEUROSCI.3536-08.2008

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by McCarthy, M. M. Articles by Kopell, N. Search for Related Content PubMed PubMed Citation Articles by McCarthy, M. M. Articles by Kopell, N.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Potential Network Mechanisms Mediating Electroencephalographic Beta Rhythm Changes during Propofol-Induced Paradoxical Excitation

Michelle M. McCarthy,¹ Emery N. Brown,^2,3 and Nancy Kopell¹

¹Department of Mathematics and Statistics, and Center for BioDynamics, Boston University, Boston, Massachusetts 02215, ²Department of Anesthesia and Critical Care, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02114, and ³Department of Brain and Cognitive Sciences, Harvard–MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

Correspondence should be addressed to Michelle M. McCarthy, Department of Mathematics and Statistics, Boston University, 111 Cummington Street, Boston, MA 02215. Email: mmccart{at}bu.edu

Propofol, like most general anesthetic drugs, can induce both behavioral and electroencephalographic (EEG) manifestations of excitation, rather than sedation, at low doses. Neuronal excitation is unexpected in the presence of this GABA_A-potentiating drug. We construct a series of network models to understand this paradox. Individual neurons have ion channel conductances with Hodgkin–Huxley-type formulations. Propofol increases the maximal conductance and time constant of decay of the synaptic GABA_A current. Networks range in size from 2 to 230 neurons. Population output is measured as a function of pyramidal cell activity, with the electroencephalogram approximated by the sum of population AMPA activity between pyramidal cells.

These model networks suggest propofol-induced paradoxical excitation may result from a membrane level interaction between the GABA_A current and an intrinsic membrane slow potassium current (M-current). This membrane level interaction has consequences at the level of multicellular networks enabling a switch from baseline interneuron synchrony to propofol-induced interneuron antisynchrony. Large network models reproduce the clinical EEG changes characteristic of propofol-induced paradoxical excitation. The EEG changes coincide with the emergence of antisynchronous interneuron clusters in the model networks. Our findings suggest interneuron antisynchrony as a potential network mechanism underlying the generation of propofol-induced paradoxical excitation. As correlates of behavioral phenomenology, these networks may refine our understanding of the specific behavioral states associated with general anesthesia.

Key words: propofol anesthesia; paradoxical excitation; GABA_A; M-current; EEG; beta rhythms

---

Received July 28, 2008; accepted Sept. 7, 2008.

Correspondence should be addressed to Michelle M. McCarthy, Department of Mathematics and Statistics, Boston University, 111 Cummington Street, Boston, MA 02215. Email: mmccart{at}bu.edu

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help