title: Postnatal subventricular zone progenitors switch their fate to generate neurons with distinct synaptic input patterns.
abstract: New granule cell neurons (GCs) generated in the neonatal and adult subventricular zone (SVZ) have distinct patterns of input synapses in their dendritic domains. These synaptic input patterns determine the computations that the neurons eventually perform in the olfactory bulb. We observed that GCs generated earlier in postnatal life had acquired an 'adult' synaptic development only in one dendritic domain, and only later-born GCs showed an 'adult' synaptic development in both dendritic domains. It is unknown to what extent the distinct synaptic input patterns are already determined in SVZ progenitors and/or by the brain circuit into which neurons integrate. To distinguish these possibilities, we heterochronically transplanted retrovirally labeled SVZ progenitor cells. Once these transplanted progenitors, which mainly expressed Mash1, had differentiated into GCs, their glutamatergic input synapses were visualized by genetic tags. We observed that GCs derived from neonatal progenitors differentiating in the adult maintained their characteristic neonatal synapse densities. Grafting of adult SVZ progenitors to the neonate had a different outcome. These GCs formed synaptic densities that corresponded to neither adult nor neonatal patterns in two dendritic domains. In summary, progenitors in the neonatal and adult brain generate distinct GC populations and switch their fate to generate neurons with specific synaptic input patterns. Once they switch, adult progenitors require specific properties of the circuit to maintain their characteristic synaptic input patterns. Such determination of synaptic input patterns already at the progenitor-cell level may be exploited for brain repair to engineer neurons with defined wiring patterns.
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim 68159, Germany German Cancer Research Center, Heidelberg 69120, Germany.
authors.forename: Namasivayam
authors.initials: N
authors.lastname: Ravi
authors.affiliation: German Cancer Research Center, Heidelberg 69120, Germany.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim 68159, Germany German Cancer Research Center, Heidelberg 69120, Germany.
authors.forename: Lars-Lennart
authors.initials: LL
authors.lastname: Oettl
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim 68159, Germany.
authors.forename: Dusan
authors.initials: D
authors.lastname: Bartsch
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim 68159, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Schönig
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim 68159, Germany German Cancer Research Center, Heidelberg 69120, Germany kelsch@uni-heidelberg.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kelsch
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D005260:Female; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D020547:Lateral Ventricles / Q000166:cytology*; D058953:Neural Stem Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013569:Synapses / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C499318:Ascl1 protein, rat
keywords: Adult neurogenesis; Fate determination; Rat; Subventricular zone; Synaptic development