CHRNA4 and Huntington disease: For example, electrical stimulation might have led to preferential activation of PT axons, which are larger and have a lower threshold for electrical stimulation18; as glutamate release by PT terminals is enhanced by ACh release and nAChR activation22 rather than being inhibited by mAChRs, their preferential recruitment in HD models—where ACh release is reduced—could have led to the appearance of impaired corticostriatal connectivity.