GABAB receptors accentuate neural excitation contrast in rat insular cortex

Synaptic transmission mediated by metabotropic GABA receptors, GABAB receptors, regulates physiological functions of cerebrocortical local circuits. It is, however, still unknown how GABAB receptors regulate excitatory propagation at more macroscopic level. We performed in vivo optical imaging to investigate the spatio-temporal profiles of GABAB receptor-mediated regulation of excitatory propagation in anesthetized rat insular cortex (IC). Repetitive electrical stimulation (a sequence of 10 pulses at 50 Hz) of the dysgranular IC (DI), a part of gustatory cortex (GC), elicited excitatory propagation along the rhinal fissure. Tonic activation of GABAB receptors by application of baclofen suppressed the optical signal amplitude to the early pulses in the sequence (first to third stimuli), typically in the rostral GC (rGC). In contrast, optical signal amplitude to later pulses was enhanced by baclofen in both the rGC and caudal GC (cGC). Baclofen reduced the area of excitation during the early pulses in the sequence but not during later pulses. Application of CGP 52432, which blocked GABAB receptor-mediated tonic and phasic inhibition, slightly suppressed optical responses to early pulses (though not to the first pulse), whereas it enhanced responses to later pulses, especially in the dorsolateral orbital cortex (DLO). Decay amplitude of the response to the first pulse was reversed to a large rise in amplitude by the GABAA receptor antagonist bicuculline. The decay amplitude was enhanced by CGP 52432 and reversed to a small rise by baclofen. This suggests that GABAB receptor activation reduced postsynaptic GABAA receptor activation indirectly via inhibition of presynaptic GABA release. Optical responses induced by DLO stimulation were reduced by pre-stimulation of the cGC 180 ms before DLO stimulation, which was blocked by CGP 52432. These results suggest that tonic and phasic activation of GABAB receptors cooperatively enhances the contrast of neural excitation at a level of millimeters.

▶Spatiotemporal profiles of neocortical excitation were examined by optical imaging. ▶In control, a GABAB agonist enhances excitation contrast depending on signal amplitude. ▶A GABAB antagonist changes the border between excited and less excited regions unclear. ▶GABAB receptors improve the signal to noise ratio at a millimeter scale in the neocortex.