The Functional Organization of Cortical and Thalamic Inputs onto Five Types of Striatal Neurons Is Determined by Source and Target Cell Identities

To understand striatal function, it is essential to know the functional organization of the numerous inputs targeting the diverse population of striatal neurons. Using optogenetics, we activated terminals from ipsi- or contralateral primary somatosensory cortex (S1) or primary motor cortex (M1), or thalamus while obtaining simultaneous whole-cell recordings from pairs or triplets of striatal medium spiny neurons (MSNs) and adjacent interneurons. Ipsilateral corticostriatal projections provided stronger excitation to fast-spiking interneurons (FSIs) than to MSNs and only sparse and weak excitation to low threshold-spiking interneurons (LTSIs) and cholinergic interneurons (ChINs). Projections from contralateral M1 evoked the strongest responses in LTSIs but none in ChINs, whereas thalamus provided the strongest excitation to ChINs but none to LTSIs. In addition, inputs varied in their glutamate receptor composition and their short-term plasticity. Our data revealed a highly selective organization of excitatory striatal afferents, which is determined by both pre- and postsynaptic neuronal identity.