Changes in Cortical Responses Caused by Learning Novel Optogenetic Stimuli



LaFosse, Paul Kristian

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Repeated experience with a sensory stimulus can cause perceptual learning, with cerebral cortical responses changing as behavioral improvement occurs. However, since sensory stimuli change the activity of neurons in many different areas of the brain, it has been unclear whether learning creates changes in the cortex, or whether changes in cortical activity reflect changes in afferent input. Here, to determine whether learning-related changes happen directly in local cortical circuits or if all changes occur in downstream areas, we take advantage of the fact animals can learn to base their behavior on non-natural (“off-manifold”) activity patterns evoked by direct stimulation, which allows us to reliably induce stimulation in the same cortical neurons on repeated trials, bypassing afferent areas. We trained mice to detect and report the presence of neural activity evoked by optogenetic stimulation (ChrimsonR in excitatory neurons of primary visual cortex, V1), and found large behavioral improvements as animals learned to detect this stimulus. Animals were first trained to detect a visual stimulus of varying contrast. An optogenetic stimulus was then paired with every visual stimulus. When performance increased for the lowest contrast visual stimulus, the visual stimulus was turned off and animals performed the task based on the optogenetic stimulus alone. As animals gained experience with the optogenetic stimulus presented alone, animals’ reaction time decreased (-15.9±3.8 ms, per training session, median±SEM, p<0.01, N=9 mice), and detection performance to the stimulus intensity improved (by over an order of magnitude). We imaged calcium responses in local V1 neurons before and after learning (before the optogenetic stimulus is presented and after animals’ detection performance for the optogenetic stimulus improved) and found changes in local cortical activity. Visual selectivity for direction and orientation was decreased by optogenetic learning, but overall neural responses became larger. These data suggest local cortical circuitry does adapt to support learning and that cortical processing of one type of stimulus (an ‘on-manifold’ visual stimulus) is degraded by learning another type of stimulus (an “off-manifold” optogenetic stimulus), while neural responses can be enhanced.



Learning, Optogenetics, Visual cortex, Two-photon imaging