Precursor Cells in the Parenchyma Act in Concert with Ventricular Neural Progenitors to Facilitate Dramatic Astrocyte Turnover and Recovery Following Natural Neuronal Death

Songbirds exhibit remarkable seasonal neuroplasticity, with song control nuclei undergoing seasonal cycles of extreme and rapid neuronal death and regeneration. While adult neurogenesis in these systems is well-characterized, the dynamics and functional significance of astrocytic turnover remain unknown. Here, we examined the fate of neural progenitor cell progeny born during seasonally-induced reactive proliferation and identified a rapid astrocytic turnover event in HVC following seasonal neuronal loss. Using lineage-specific and proliferation labeling, we characterized a previously undescribed SOX2-positive neural progenitor-like population within the avian parenchyma beyond the canonical ventricular zone niche. These parenchymal astrocyte precursor cells (pAPCs) proliferate at quantifiable, steady levels under homeostatic conditions, yet as a proliferative cell pool dramatically expand following non-injury induced neuronal death. Beyond their proliferative potential, pAPCs demonstrate capabilities suggestive of self-renewal and generation of astrocytes and neurons. The coordinated response of canonical neural progenitor cells and the newly-described pAPCs generates new astrocytes that persist throughout re-establishment of homeostasis, all of which together likely facilitate subsequent circuit regrowth. These findings reveal extensive astrocyte plasticity in the adult avian telencephalon and establish a foundation for understanding how astrocytes and their precursors--both within and beyond their canonical niches--contribute to neural circuit remodeling and behavioral maintenance. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/717664v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@15437e6org.highwire.dtl.DTLVardef@221e58org.highwire.dtl.DTLVardef@1f65df2org.highwire.dtl.DTLVardef@191ca3c_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO C_FIG HighlightsO_LISubstantial astrocyte turnover following a natural, extreme neuronal death event C_LIO_LIDiscovery of proliferative SOX2 positive precursor cells within the avian parenchyma C_LIO_LIThese parenchymal astrocyte precursor cells (pAPCs) proliferate even in homeostasis C_LIO_LIThe proliferative pAPC pool expands during the natural neuronal death event C_LIO_LIDynamics in both NPCs and pAPCs contribute to homeostasis return and potentially enable circuit regrowth C_LI