Expression levels of α5 subunit-containing GABA-A receptors in the prelimbic cortex are associated with visual perceptual learning

Abstract

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. Significance statementCortical inhibitory microcircuits underlie visual perceptual learning (VPL) and may contribute to altered perceptual learning in neurodevelopmental disorders. However, the mechanisms underlying VPL are poorly understood. This study implemented a translationally relevant touchscreen task to assess visual perception and attention. We report that 5-subunit containing GABA-A receptors (GABRA5) are decreased in expression in the prelimbic subregion of the prefrontal cortex in animals that are slower to acquire the VPL task compared with animals showing superior VPL. We also report that VPL can be improved in a subset of poor learning animals by a positive allosteric modulator of GABRA5. These findings suggest that GABRA5 may be a potential therapeutic target to improve visual perception in schizophrenia and other neurodevelopmental disorders.