Long-term potentiation (LTP) is a form of experimentally induced enhancement of chemical synaptic transmission that has long been proposed as a model of the endogenous processes of synaptic plasticity that mediate memory. There is a large body of evidence that the molecular mechanisms underlying experimentally induced LTP also subserve various forms of naturally occurring, experience-dependent synaptic plasticity in animals and humans. Here we describe a phenomenon called stimulus-specific response potentiation (SRP), which occurs in the primary visual cortex of mice as a result of repeated exposure to visual stimuli and is believed to reveal the mechanisms that underlie perceptual learning. We first describe evidence that SRP represents naturally occurring LTP of thalamo-cortical synaptic transmission. We then discuss the potential value of SRP as a preclinical assay for the assessment of putative drug treatments on synaptic plasticity. Stimulus-specific response potentiation is not only easy to assay and robust but captures features of feed-forward glutamatergic function and visual learning that are deficient in human psychiatric disorders, notably including schizophrenia. We suggest that phenomena analogous to SRP in humans are likely to be useful biomarkers of altered cortical LTP and of treatment response in diseases associated with impaired cognition.