Distinct Embryonic Progenitor Pools in the Ventral Telencephalon Generate Fine-Scale Striatal Synaptic Circuits

Abstract

Synaptic circuits in the brain are precisely organized, but the processes that govern this precision are poorly understood. Here we explored how distinct embryonic neural progenitor pools in the lateral ganglionic eminence (LGE) contribute to the synaptic circuit connectivity and neuronal diversity in the postnatal mouse striatum. In utero labeling of apical intermediate progenitors (aIP), as well as other progenitors (OP), revealed that both generate spiny projection neurons (SPNs), consisting of D1-expressing direct pathway (dSPNs) as well as D2-expressing indirect pathway (iSPNs) found intermingled in the medial aspects of striatum, with similar electrophysiological and anatomical properties. Subsequent optogenetic circuit-mapping of local synaptic connections between these SPNs showed that neurogenic stage rather than progenitor origin controls the strength of lateral GABAergic connections. However, embryonic progenitor origin conveyed strong biases in their long-range cortical inputs, in that aIP-derived SPNs were preferentially driven by inputs from the medial prefrontal cortex whereas OP-derived SPNs were strongly driven by inputs from the visual cortex. Combined, these results demonstrate critical roles for embryonic origin in shaping the inhibitory and excitatory synaptic circuits in the striatum.