Genetic-Based Dissection Unveils the Inputs and Outputs of Striatal Patch and Matrix Compartments

The striatum contains neurochemically defined compartments termed patches and matrix. Previous studies suggest patches preferentially receive limbic inputs and project to dopamine neurons in substantia nigra pars compacta (SNc), whereas matrix neurons receive sensorimotor inputs and do not innervate SNc. Using BAC-Cre transgenic mice with viral tracing techniques, we mapped brain-wide differences in the input-output organization of the patch/matrix. Findings reveal a displaced population of striatal patch neurons termed exo-patch,'' which reside in matrix zones but have neurochemistry, connectivity, and electrophysiological characteristics resembling patch neurons. Contrary to previous studies, results show patch/exo-patch and matrix neurons receive both limbic and sensorimotor information. A novel inhibitory projection from bed nucleus of the stria terminalis to patch/exo-patch neurons was revealed. Projections to SNc were found to originate from patch/exo-patch and matrix neurons. These findings redefine patch/matrix beyond traditional neurochemical topography and reveal new principles about their input-output connectivity, providing a foundation for future functional studies.