Abstract
SummaryThe potential for neuronal representations of external stimuli to be modified by previous experience is critical for efficient sensory processing and improved behavioral outcomes. To investigate how repeated exposure to a visual stimulus affects its representation in mouse primary visual cortex (V1), we performed two-photon calcium imaging of layer 2/3 neurons and assessed responses before, during, and after the presentation of a repetitive stimulus over 5 consecutive days. We found a stimulus-specific enhancement of the neuronal representation of the repetitively presented stimulus when it was associated with a reward. This was observed both after mice actively learned a rewarded task and when the reward was randomly received. Stimulus-specific enhanced representation resulted both from neurons gaining selectivity and from increased response reliability in previously selective neurons. In the absence of reward, there was either no change in stimulus representation or a decreased representation when the stimulus was viewed at a fixed temporal frequency. Pairing a second stimulus with a reward led to a similar enhanced representation and increased discriminability between the equally rewarded stimuli. Single-neuron responses showed that separate subpopulations discriminated between the two rewarded stimuli depending on whether the stimuli were displayed in a virtual environment or viewed on a single screen. We suggest that reward-associated responses enable the generalization of enhanced stimulus representation across these V1 subpopulations. We propose that this dynamic regulation of visual processing based on the behavioral relevance of sensory input ultimately enhances and stabilizes the representation of task-relevant features while suppressing responses to non-relevant stimuli.
Highlights
We found a stimulus-specific enhancement of the neuronal representation of the repetitive stimulus when it was associated with a reward
We characterized the visual responses of layer 2/3 neurons expressing the genetically encoded calcium indicator GCaMP6 [37] in V1 by using two-photon calcium imaging in head-fixed mice that were freely running on a cylindrical treadmill (Figure 1)
Animals were presented with only a single oriented grating for 5 consecutive days, followed by a second assessment of visual responses to all oriented gratings at the end of the experiments
Summary
Surgery For cranial window implantation and virus injection, mice were anaesthetized with isoflurane (4% for induction and 1%–2% maintenance during surgery) and mounted on a stereotaxic frame (David Kopf Instruments). Syn.GCaMP6f.WPRE.-SV40 (RRID:Addgene_100837) was injected in V1; GCaMP6s was used for all experimental groups except for the 5 mice trained for both phase 1 and phase 2 in goal-directed VR group, for which we used GCaMP6f [see Table S1]; note, there were no significant differences in responses to the repetitive grating between the GCaMP6s and GCaMP6f expressing mice for the goal-directed VR group in phase 1, so results were pooled, see Figure 4F). Pipettes were left in situ for an additional 5 min to prevent backflow. After recovery from anesthesia, animals were returned to their home cage for 2-3 weeks to allow for virus expression and clearing of the cranial window [68] before imaging
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