Development and plasticity of stimulus processing in the visual cortex

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Abstract During postnatal development sensory systems become adapted, through experience, to extract features from complex natural environments. Transient deprivation of visual input during this sensitive period permanently disrupts visual function. Once mature, these circuits are stabilized and do not require continuous visual input to maintain function. Traditionally, development and rescue of vision is studied using simple oriented bars of light composed of varying spatial frequencies (grating stimuli). Although grating stimuli effectively drive the majority of neurons in the primary cortex (V1) and are the stimuli used to define developmental milestones such as binocular alignment between the two eyes, it is well-recognized that simple grating stimuli are not the preferred stimuli for most neurons in adult V1, across a range of species. Furthermore, selectivity to complex features cannot be explained by response profiles evoked by simple stimuli; this is likely a general principle for multiple sensory modalities. It is unknown when responses to complex features become mature, nor whether interventions that improve grating spatial acuity rescue binocular vision or complex responses in amblyopic mice. To fill this gap in knowledge we will define the developmental trajectory of complex responses relative to established milestones, and identify conditions that facilitate the rescue of complex-feature processing in visually deprived mice. Neural activity in binocular V1 will be longitudinally monitored using 2-photon calcium imaging in control and deprived mice, in combination with cell-type specific manipulation. Responses to grating and complex stimuli will be assessed at the single-neuron and population levels. We recently demonstrated that visual experience drives a shift in preference for complexity; the timing of this maturation occurs after the peak of the critical period. Based on these results, in Aim 1 we will test the hypothesis that complex-feature responses remain sensitive to visual deprivation past the classically defined critical period, and complex-feature processing continues to develop as animals expand their visually-guided behavioral repertoire. Accumulating evidence indicates that somatostatin (SOM) in coordination with vasoactive intestinal peptide (VIP) inhibitory interneurons mediate contextual surround modulation, a property that is fundamental to processing complex scenes. Therefore, in Aim 2 we will characterize the maturation of SOM responses and the stabilization of grating- response tuning relative to the emergence of complex-feature responses. Finally, in Aim 3 we will test the hypothesis that enriched experience, in the form of association training, accelerates the stabilization of binocular alignment and improves complex-feature processing in amblyopic mice when proceeded by rejuvenating dark exposure. Successful completion of these aims will provide crucial cell-type specific details regarding how responses to complex features emerge from a network comprised of neurons innately tuned to simple grating stimuli in healthy and amblyopic mice.