RAPID COMMUNICATION Adrenoceptor-Mediated Elevation of Ambient GABA Levels Activates Presynaptic GABAB Receptors in Rat Sensorimotor Cortex

Bennett, Ben D., John R. Huguenard, and David A. Prince. blockade of GABA uptake (Isaacson et al. 1993; Thompson Adrenoceptor-mediated elevation of ambient GABA levels actiand Gähwiler 1992), application of convulsant drugs (Otis vates presynaptic GABAB receptors in rat sensorimotor cortex. J. and Mody 1992; Scanziani et al. 1991), or electrical stimulaNeurophysiol. 78: 561–566, 1997. At inhibitory synapses in the tion (Otis and Mody 1992), cause activation of GABAB mature neocortex and hippocampus in vitro, spontaneous actionreceptors. potential-dependent and -independent release of g-aminobutyric The circumstances that normally lead to such elevations in acid (GABA) activates postsynaptic GABAA receptors but not preextracellular GABA and recruitment of presynaptic GABAB or postsynaptic GABAB receptors. Elevation of synaptic GABA receptors in cortical circuits are unclear. One candidate levels with pharmacological agents or electrical stimulation can mechanism might be an increase in spontaneous GABA recause activation of GABAB receptors, but the physiological conditions under which such activation occurs need further elucidation. lease. Epinephrine (EPI) increases the frequency of spontaIn rodent sensorimotor cortex, epinephrine produced a depression neous inhibitory postsynaptic currents (IPSCs) in neurons of in the amplitude of evoked monosynaptic inhibitory postsynaptic rat sensorimotor cortical slices by activating a-adrenoceptors currents (IPSCs) and a concomitant, adrenoceptor-mediated in(Bennett et al. 1995), and concurrently causes a reduction crease in the frequency of spontaneous IPSCs. Blockade of GABAB in the amplitude of monosynaptic evoked IPSCs in the mareceptors prevented the depression of evoked IPSC amplitude by jority of neurons tested (see below). We conducted experiepinephrine but did not affect the increase in spontaneous IPSC ments to investigate the possibility that EPI might be producfrequency. These data show that adrenoceptor-mediated increases ing a depression in evoked IPSC amplitude as a result of ain spontaneous IPSCs can cause activation of presynaptic GABAB adrenoceptor-mediated increases in spontaneous IPSCs that receptors and indirectly modulate impulse-related GABA release, elevate synaptic GABA levels and cause activation of prepresumably through elevation of synaptic GABA levels. synaptic GABAB receptors.