Science, Medicine, and the Anesthesiologist

The neuronal mechanisms of general anesthetics are attributed to multiple cellular targets including postsynaptic potentiation of inhibitory ion channels and the inhibition of neurotransmitter release by interference with proteins involved in exocytosis; however, variation may exist in the cellular targets of anesthetics among synapse subtypes. In the current study, isoflurane’s effects on neurotransmitter release at cholinergic neurons in insect mushroom body output neurons (MBON) of female Drosophilia brains was measured. Anesthesia was defined as an absence of behavioral responsiveness to mechanical stimulation. Isoflurane immobilized and clustered syntaxin1a, a key component of the SNARE protein complex, essential for neurotransmitter release. In contrast, isoflurane did not effect syntaxin1a mobility or clustering in GABAergic or glutamatergic synapses in the MBON. The difference between isoflurane’s effects on cholinergic versus GABAergic synapses was not attributable to variation in neuronal stimulation measured by calcium transients. These results suggest that isoflurane inhibits presynaptic release of neurotransmitter at cholinergic neurons while potentiating postsynaptic GABAergic and glutamatergic inhibitory neuronal activity. It is concluded that variations in the specific proteins of the exocytotic protein complex, rather than the specific neurotransmitter released, may account for differential effects of anesthetics on excitatory cholinergic system versus the inhibitory GABAergic and glutamatergic circuits.