Differential effects of isoflurane on excitatory and inhibitory synaptic inputs to thalamic neurones in vivo

Background. Mechanosensory thalamocortical relay neurones (TCNs) receive glutamatergic excitatory input and are subjected to gamma-aminobutyric acid (GABA)(A)ergic inhibitory input. This study assessed the effects of an increase in concentration of isoflurane on thalamic excitatory and inhibitory mechanisms. Methods. TCNs (n=15) of the thalamic ventral posteromedial nucleus responding to mechanical stimulation of whiskers were investigated in rats anaesthetized with end-tidal concentrations of isoflurane of similar to0.9% (ISOlow, baseline) and similar to1.9% (ISOhigh). Response activity induced by controlled vibratory movement of single whiskers was recorded before, during and after iontophoretic administration of the GABA(A) receptor antagonist bicuculline to the vicinity of the recorded neurone. Results. The increase in concentration of isoflurane induced a suppression of vibratory responses to 14 (4)% [mean (sem)] of baseline activity. Blockade of GABA(A) receptors by bicuculline during ISOlow and ISOhigh caused increases in response activity to 259 (32)% and 116 (25)% of baseline activity, respectively. The increase in isoflurane concentration enhanced overall inhibitory inputs by 102 (38)%, whilst overall excitatory inputs were reduced by 54 (7)%. Conclusions. These data suggest that doubling the concentration of isoflurane doubles the strength of GABA(A)ergic inhibition and decreases the excitatory drive of TCNs by approximately 50%. The isoflurane-induced enhancement of GABA(A)ergic inhibition led to a blockade of thalamocortical information transfer which was not accomplished by the effects of isoflurane on glutamatergic synaptic transmission alone. Thus, it appears that, with respect to transmission of information in the thalamus, the most prominent action of isoflurane is an enhancement of GABA(A)ergic synaptic inhibition, and that effects on glutamatergic neurotransmission may contribute to a lesser extent.