Investigation into the effect of the general anaesthetics etomidate and ketamine on long-range coupling of population activity in the mouse neocortical slice.
General anaesthetics have been hypothesised to ablate consciousness by decoupling intracortical neural connectivity. We explored this by investigating the effect of etomidate and ketamine on coupling of neural population activity using the low magnesium neocortical slice model. Four extracellular electrodes (50 μm) were positioned in mouse neocortical slices (400 μm thick) with varying separation. The effect of etomidate (24 μM) and ketamine (16 μM) on the timing of population activity recorded between channels was analysed. No decoupling was observed at the closest electrode separation of 0.2 mm. At 4mm separation, decoupling was observed in 50% and 42% of slices during etomidate and ketamine delivery, respectively (P<0.0001 and P=0.002, compared to 0.2 mm separation). A lower rate of decoupling was observed with 1mm separation (21% and 8%, respectively, P<0.03 for etomidate compared to 0.2mm separation). The data support the hypothesis that mechanistically diverse general anaesthetics disrupt neuronal connectivity across widely distributed intracortical networks.
Waikato District Health Board, Anaesthesia Department, Pembroke Street, Hamilton 3204, New Zealand. vossl@waikatodhb.health.nz
Logan J
LJ
Voss
Cecilia Hansson
CH
Baas
Linnea
L
Hansson
D Alistair
DA
Steyn-Ross
Moira
M
Steyn-Ross
James W
JW
Sleigh
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D018681:Anesthetics, General / Q000494:pharmacology*; D000818:Animals; D005045:Etomidate / Q000494:pharmacology*; D005260:Female; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques
D018681:Anesthetics, General; D007649:Ketamine; D005045:Etomidate