Detection of novel stimuli that may predict reward or punishment requires long-term memory for, and recognition of, stimuli that are familiar. Novelty detection and familiarity recognition are often impaired in neuropsychiatric disease, so understanding the neurobiological underpinnings is an important goal. We recently discovered that memory of visual stimulus familiarity is stored via synaptic modifications in primary visual cortex of mice. The primary aims of our research are now to (a) identify how information is stored by the collective activity of neurons in primary visual cortex, (b) pinpoint the key sites in the cortical microcircuit where the essential synaptic modifications occur, and (c) examine a specific hypothesis that memory is expressed by switching the state of activity in the reciprocal connections between visual cortex and thalamus. Beyond the relevance of our proposed research to identifying the mechanisms underlying visual recognition memory, they will broaden our understanding of how primary sensory areas are modified by sensory experience in order to modify behavior, which remains one of the great challenges in basic neuroscience.