Distinct neural progenitor pools in the ventral telencephalon generate diversity in striatal spiny projection neurons

Abstract

Heterogeneous populations of neural progenitors in the embryonic lateral ganglionic eminence (LGE) generate all GABAergic spiny projection neurons (SPNs) found in the striatum. Here we investigate how this diversity in neural progenitors relates to diversity of adult striatal neurons and circuits. Using a combination of in utero electroporation to fluorescently pulse-label striatal neural progenitors in the LGE, brain slice electrophysiology, electrical and optogenetic circuit mapping and immunohistochemistry, we characterise a population of neural progenitors enriched for apical intermediate progenitors (aIPs) and a distinct population of other progenitors (OPs) and their neural offspring. We find that neural progenitor origin has subtle but significant effects on the properties of striatal SPNs. Although aIP and OP progenitors can both generate D1-expressing direct pathway as well as D2-expressing indirect pathway SPNs found intermingled in the striatum, the aIP derived SPNs are found in more medial aspects of the striatum, exhibit more complex dendritic arbors with higher spine density and differentially sample cortical input. Moreover, optogenetic circuit mapping of the aIP derived neurons show that they further integrate within striatal circuits and innervate both local D1 and D2 SPNs. These results show that it is possible to fluorescently pulse-label distinct neural progenitor pools within the LGE and provide the first evidence that neural progenitor heterogeneity can contribute to the diversity of striatal SPNs.

Nfib regulates progenitor competence in maturation of GABAergic neurons

“…If not through a sequential mechanism, what drives diversity within the GE? Other factors, such as the mode of cell-division (Petros et al, 2015;Kelly et al, 2018), cell-cycle length (Glickstein et al, 2007;Lodato et al, 2011;Zong et al, 2022), progenitor heterogeneity (van Heusden et al, 2021), spatial subdomains, and transcription factors that transduce patterning signals (Rubenstein and Puelles, 1994;Shimamura et al, 1995;Wichterle et al, 2001;Nery et al, 2002;Xu et al, 2004;Wonders and Anderson, 2006;Flames et al, 2007;Fragkouli et al, 2009;Flandin et al, 2010;Sandberg et al, 2016;Dvoretskova et al, 2023) et al, 2012), Gad2¡tm1(cre/ERT2)Zjh¿ (Gad2-CreER, JAX:010702) (Taniguchi et al, 2011), Ai65(RCFL-tdT)-D (Ai65D, JAX:021875) (Madisen et al, 2015). Embryos were staged in days post-coitus, with e0.5 defined as 12:00 of the day a vaginal plug was detected after overnight mating.…”