Slow GABA A mediated synaptic transmission in rat visual cortex

摘要

Background Previous reports of inhibition in the neocortex suggest that inhibition is mediated predominantly through GABA_A receptors exhibiting fast kinetics. Within the hippocampus, it has been shown that GABA_A responses can take the form of either fast or slow response kinetics. Our findings indicate, for the first time, that the neocortex displays synaptic responses with slow GABA_A receptor mediated inhibitory postsynaptic currents (IPSCs). These IPSCs are kinetically and pharmacologically similar to responses found in the hippocampus, although the anatomical specificity of evoked responses is unique from hippocampus. Spontaneous slow GABA_A IPSCs were recorded from both pyramidal and inhibitory neurons in rat visual cortex. Results GABA_A slow IPSCs were significantly different from fast responses with respect to rise times and decay time constants, but not amplitudes. Spontaneously occurring GABA_A slow IPSCs were nearly 100 times less frequent than fast sIPSCs and both were completely abolished by the chloride channel blocker, picrotoxin. The GABA_A subunit-specific antagonist, furosemide, depressed spontaneous and evoked GABA_A fast IPSCs, but not slow GABA_A-mediated IPSCs. Anatomical specificity was evident using minimal stimulation: IPSCs with slow kinetics were evoked predominantly through stimulation of layer 1/2 apical dendritic zones of layer 4 pyramidal neurons and across their basal dendrites, while GABA_A fast IPSCs were evoked through stimulation throughout the dendritic arborization. Many evoked IPSCs were also composed of a combination of fast and slow IPSC components. Conclusion GABA_A slow IPSCs displayed durations that were approximately 4 fold longer than typical GABA_A fast IPSCs, but shorter than GABA_B-mediated inhibition. The anatomical and pharmacological specificity of evoked slow IPSCs suggests a unique origin of synaptic input. Incorporating GABA_A slow IPSCs into computational models of cortical function will help improve our understanding of cortical information processing.