Isoflurane blocks synaptic plasticity in the mouse hippocampus

Background: The volatile anesthetic isoflurane depresses glutamatergic tran smission. In this study, the authors investigated the effects of isoflurane on the induction of long-term potentiation (LTP) and long-term depression (LTD) in slices from the juvenile and adult mouse hippocampus. Both forms o f synaptic plasticity involve the activation of glutamate receptors. Methods: Field excitatory postsynaptic potentials and excitatory postsynapt ic currents from neurons in the CA1 area were evoked by stimulation of the Schaffer collateral-commissural pathway. Two independent synaptic inputs we re stimulated, Clinically relevant concentrations (0.2-0.3 mM) of isofluran e mere added to the perfusion solution. Results: Field excitatory postsynaptic potentials from slices of juvenile a nd adult mice mere depressed to 37.3 +/- 6.1% and 58.3 +/- 7.4%, respective ly, and excitatory postsynaptic currents were reduced to 36.7 +/- 5.4% by i soflurane. A brief tetanic stimulation (100 Hz, 1 s) induced stable LTP of field excitatory postsynaptic potentials. In the presence of isoflurane, te tanization failed to induce LTP. The effect of isoflurane on LTP induction was reversible and could be prevented by antagonizing gamma -aminobutyric a cid type A receptors (GABA(A)). Low-frequency stimulation (1 Hz/900 pulses) induced LTD. In the presence of isoflurane, ion-frequency stimulation fail ed to induce LTD. Conclusions: The prevention of the isoflurane-induced depression of LTP by the GABA, antagonist picrotoxin suggests an involvement of GABA, receptors. An enhancement of the efficacy of GABA-mediated inhibitory synaptic transm ission prevents the depolarization of the postsynaptic membrane during teta nus, necessary for the induction of use-dependent alteration of synaptic st rength. An impairment of these processes may be a cause for the transient l oss of recall and cognitive impairment after anesthesia in juvenile and adu lt brains.