Adrenoceptor-Mediated Elevation of Ambient GABA Levels Activates Presynaptic GABABReceptors in Rat Sensorimotor Cortex

Bennett, Ben D., John R. Huguenard, and David A. Prince.Adrenoceptor-mediated elevation of ambient GABA levels activates presynaptic GABABreceptors in rat sensorimotor cortex. J. Neurophysiol.78: 561–566, 1997. At inhibitory synapses in the mature neocortex and hippocampus in vitro, spontaneous action-potential-dependent and -independent release of γ-aminobutyric acid (GABA) activates postsynaptic GABAAreceptors but not pre- or postsynaptic GABABreceptors. Elevation of synaptic GABA levels with pharmacological agents or electrical stimulation can cause activation of GABABreceptors, but the physiological conditions under which such activation occurs need further elucidation. In rodent sensorimotor cortex, epinephrine produced a depression in the amplitude of evoked monosynaptic inhibitory postsynaptic currents (IPSCs) and a concomitant, adrenoceptor-mediated increase in the frequency of spontaneous IPSCs. Blockade of GABABreceptors prevented the depression of evoked IPSC amplitude by epinephrine but did not affect the increase in spontaneous IPSC frequency. These data show that adrenoceptor-mediated increases in spontaneous IPSCs can cause activation of presynaptic GABABreceptors and indirectly modulate impulse-related GABA release, presumably through elevation of synaptic GABA levels.