Prefrontal 5-GABA-A receptors: putative role in perceptual learning

Perceptual learning is a dynamic process involving the acquisition and integration of sensory information necessary for adaptive decision making. Resolving the neural basis of perceptual learning may have relevance for our understanding of schizophrenia and other neurodevelopmental disorders that implicate impaired perceptual acuity. We developed a novel touchscreen task that utilizes orientation discrimination and variable attentional load to elucidate the perceptual and attentional components of visual perceptual learning (VPL) in male and female rats. Based on previous evidence we hypothesised that individual variation in VPL may depend in part on inhibitory neurotransmission mediated by {gamma}-amino butyric acid (GABA). Segregating subjects based on 'poor' and 'good' learning after task pretraining revealed dose-dependent improvements in VPL in poor learners following the administration of an 5 subunit specific GABA-A (GABRA5) positive allosteric modulator (Alogabat) and a GABA-B agonist (R-baclofen) early in learning. Poor VPL performance was associated with significantly reduced GABRA5 mRNA expression in dorsal regions of the prefrontal cortex (PFC), notably the prelimbic cortex. Decreased GABRA5 expression in this region was co-localized to somatostatin- and parvalbumin-expressing interneurons. These findings reveal a potential link between GABRA5 expression in selective PFC populations of inhibitory interneurons and the speed and acuity of VPL.