Lateralized foraging induces asymmetric corticostriatal plasticity in mice

With practice, animals perform reward-oriented actions faster and with less variability. The dorsal striatum plays a key role in this process, potentially through opposing changes in cortical input strength to the two main striatal projection neurons (D1-SPNs and D2-SPNs). To test this hypothesis, we trained mice in a foraging task requiring them to perform quarter-turns (QTs) in a single direction (counterclockwise, CCW) along the walls of square towers to collect drops of water. As training progressed, the number and speed of CCW QTs increased while the variability of their trajectory decreased. Whisker trimming in well-trained mice altered QTs kinematics, highlighting the role of tactile inputs in guiding these actions. Combining ex vivo patch-clamp recordings in the striatum with glutamate uncaging in the barrel cortex, we mapped the cortical neurons monosynaptically connected to D1-SPNs or D2-SPNs and measured the strength of these connections in the contralateral hemispheres, relative to the turn direction. In well-trained mice, compared to naïve controls, the contralateral hemisphere showed no major changes in D1-SPNs or D2-SPNs connectivity, despite increased excitation of cortical pyramidal neurons. In contrast, the ipsilateral hemisphere exhibited no such increase in cortical excitability but instead exhibited a marked expansion of cortical inputs onto SPNs. These findings reveal an unexpected hemispheric asymmetry in corticostriatal connectivity during lateralized foraging, which may reflect a homeostatic process normalizing striatal activity across hemispheres despite unbalanced cortical input.