Investigation into the role of gap junction modulation of intracortical connectivity in mouse neocortical brain slices.
General anesthetics are hypothesized to cause unconsciousness by interrupting communication pathways within the cerebral cortex. A correlate of this has been demonstrated in mouse neocortical slices, where anesthetics disrupt the spread of population field potential activity--resulting in a "decoupling" of activity recorded across spatial locations within the slice. In this study we investigated whether this decoupling can be explained by gap junction blockade, with a particular focus on the connexin36 (Cx36) subtype. Baseline, coupled seizure-like event (SLE) activity was recorded from two extracellular electrodes in slices perfused with no-magnesium artificial cerebrospinal fluid (aCSF). The connexin36 gap junction blocker mefloquine (25 µM) failed to decouple SLE activity in wild-type mice (median(range) decoupling rate of 0.70(0.03-3.00)%, not significantly different from controls). Slices from Cx36 knock-out mice exhibited coupled SLE activity under baseline conditions and readily decoupled when exposed to the general anesthetic etomidate. The general gap junction blocker carbenoxolone (CBX, 100 µM) strongly decoupled SLE activity compared to controls in wild-type mice (2.7(0.1-42.5) % compared to 0.03(0.0-0.5)%, p=0.0001). Taken together, the results show that Cx36 gap junction blockade does not cause decoupling of intracortical population activity, but the involvement of other gap junction subtypes cannot be ruled out.
Anaesthesia Department, Waikato District Health Board, Hamilton, New Zealand. Electronic address: Logan.Voss@waikatodhb.health.nz.
Logan J
LJ
Voss
Faculty of Health Sciences, Linköping University, Sweden. Electronic address: emega718@student.liu.se.
Emelie
E
Gauffin
Faculty of Health Sciences, Linköping University, Sweden. Electronic address: aleri529@student.liu.se.
Alexandra
A
Ringqvist
Department of Anaesthesiology, University of Auckland, New Zealand. Electronic address: Jamie.Sleigh@waikatodhb.health.nz.
James W
JW
Sleigh
D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D002491:Central Nervous System Agents / Q000494:pharmacology; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D004566:Electrodes; D005045:Etomidate / Q000494:pharmacology; D005110:Extracellular Space; D005260:Female; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology*; D019695:Glycyrrhizic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D015767:Mefloquine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019579:Neocortex / Q000187:drug effects* / Q000502:physiology*; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D000097004:Gap Junction delta-2 Protein
D018686:Anesthetics, Intravenous; D002229:Carbenoxolone; D002491:Central Nervous System Agents; D017630:Connexins; D005045:Etomidate; D019695:Glycyrrhizic Acid; D015767:Mefloquine; D000097004:Gap Junction delta-2 Protein
Anesthesia; Consciousness; Cortical slice; Decoupling; Gap junctions; Mouse