Pyramidal tract neurons drive feed-forward excitation of striatum through cholinergic interneurons

Corticostriatal connectivity is central for many cognitive and motor processes, such as reinforcement or action initiation and invigoration. The cortical input to the striatum arises from two main cortical populations: intratelencephalic (IT) and pyramidal tract (PT) neurons. We uncovered a new feedforward excitatory circuit, supported by a polysynaptic motif from PT neurons to cholinergic interneurons (ChIs) to excitatory inputs, which runs in parallel to the canonical monosynaptic corticostriatal connection. This new motif conveys a delayed second phase of excitation to striatal spiny projection neurons (SPNs), through an acetylcholine-dependent glutamate release mechanism, resulting in biphasic corticostriatal signals. These biphasic signals are a hallmark of PT, but not IT, corticostriatal inputs, due to a stronger relative input from PT neurons to ChIs. These results uncover a novel feed-forward circuit mechanism by which PT activity differentially gates excitatory inputs to the striatum, with potential implications for behavior, plasticity and learning. Highlights ### Competing Interest Statement The authors have declared no competing interest.