Two-Photon Imaging of Striatum Demonstrates Distinct Functions for Striosomes and Matrix in Reinforcement Learning

Despite the discovery of striosomes several decades ago, technical difficulties have hampered the study of their functions. Here we used 2-photon calcium imaging in neuronal birthdate-labeled Mash1-CreER mice to image simultaneously the activity of striosomal and matrix neurons in vivo. We report that with this method we can visually identify circumscribed zones of neuropil that correspond to striosomes as verified in immunostained sections. We find that striosomal neurons, relative to matrix neurons, preferentially encode reward-predicting cues, and that their activity contains more information about expected outcome. These characteristics emerge during training and further strengthen during overtraining. Both striatal compartments are active similarly after reward delivery, firing at neuron-specific times during or after consummatory licking. Finally, we find that immediate reward history strongly modulates neuronal activation in the next trial, especially in matrix neurons. These results suggest that striosomes and matrix have distinct functions in relation to reinforcement learning.