Chronic downregulation of parvalbumin-positive cell activity accelerates early perceptual learning but impairs end performance

Abstract

Parvalbumin-positive (PV+) interneurons are major regulators of adult experience-dependent plasticity. Acute manipulation of PV+ cell activity before learning alters the rate of acquisition of new skills, whereas transient inactivation of PV+ cells interferes with retrieval of previously learned information. However, the effects of sustained PV+ cell manipulation throughout training remain largely unknown. Using chemogenetics in rat auditory cortex during an adaptive sound disrimination task, here we show that PV+ cells exert bidirectional control over the rate of perceptual learning. Down-regulation of PV+ cell activity accelerated learning, but increasing their activity resulted in slower learning. However, both interventions led to reduced gains in perceptual acuity by the end of training relative to controls. Furthermore, longitudinal training performance was functionally correlated with measures of neural synchrony and stimulus-specific adaptation. These findings suggest that, whereas restricting PV+ cell activity may initially facilitate training-induced plasticity, a subsequent increase in PV+ cell activity is necessary to prevent further plastic changes and consolidate learning.