| First Author | Mesbah-Oskui L | Year | 2014 |
| Journal | J Neurosci | Volume | 34 |
| Issue | 37 | Pages | 12253-66 |
| PubMed ID | 25209268 | Mgi Jnum | J:273142 |
| Mgi Id | MGI:6283907 | Doi | 10.1523/JNEUROSCI.0618-14.2014 |
| Citation | Mesbah-Oskui L, et al. (2014) Thalamic delta-subunit containing GABAA receptors promote electrocortical signatures of deep non-REM sleep but do not mediate the effects of etomidate at the thalamus in vivo. J Neurosci 34(37):12253-66 |
| abstractText | Extrasynaptic delta-subunits containing GABAA receptors (deltaGABAARs) are sensitive targets for several commonly used hypnotic agents and mediate tonic neuronal inhibition. deltaGABAARs are highly expressed within the thalamus and their activation promotes a switch from tonic to burst firing in vitro. Here we test two hypotheses in vivo. (1) Activation of thalamic deltaGABAARs will elicit electrocortical signatures consistent with widespread thalamocortical burst firing such as increased delta oscillations (1-4 Hz) and reciprocal changes in spindle-like oscillations (7-14 Hz). (2) These signatures will be recapitulated by the general anesthetic etomidate, if the electrocortical effects of etomidate at the thalamus are mediated by deltaGABAARs. Microperfusion of the deltaGABAAR-preferring agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP; 10 and 50 muM) into the ventrobasal complex produced significant effects on electrocortical activity in wild-type mice, but not in mice lacking deltaGABAARs (Gabrd(-/-)), i.e., the effects with THIP were dependent on deltaGABAARs. THIP (1) increased 1-4 Hz power in wakefulness and nonrapid-eye movement (NREM) sleep; (2) reduced spindle-like oscillations in NREM sleep; and (3) increased the speed of stable transitions into NREM sleep, indicating effects on state-space dynamics. In contrast, microperfusion of etomidate (10 and 30 muM) into the ventrobasal complex produced effects on electrocortical activity that were independent of deltaGABAARs, i.e., effects occurred in wild-type and Gabrd(-/-) mice. Etomidate (1) decreased 1-4 Hz power, increased 8-12 Hz, and/or 12-30 Hz power in all sleep-wake states; (2) increased spindle-like oscillations; and (3) increased REM sleep expression. These results indicate that thalamic deltaGABAARs promote electrocortical signatures of deep NREM sleep, but do not mediate the effects of etomidate at the thalamus in vivo. |
