TY - JOUR T1 - Neural precursor cells contribute to decision-making by tuning striatal connectivity via secretion of IGFBPL-1 JF - bioRxiv DO - 10.1101/2020.12.29.424678 SP - 2020.12.29.424678 AU - Erica Butti AU - Stefano Cattaneo AU - Marco Bacigaluppi AU - Marco Cambiaghi AU - Giulia Scotti AU - Elena Brambilla AU - Giacomo Sferruzza AU - Maddalena Ripamonti AU - Fabio Simeoni AU - Laura Cacciaguerra AU - Aurora Zanghì AU - Angelo Quattrini AU - Riccardo Fesce AU - Paola Panina-Bordignon AU - Francesca Giannese AU - Davide Cittaro AU - Tanja Kuhlmann AU - Patrizia D’Adamo AU - Maria Assunta Rocca AU - Stefano Taverna AU - Gianvito Martino Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/12/29/2020.12.29.424678.abstract N2 - The adult brain retains endogenous neural stem/precursors cells (eNPCs) in two major neurogenic niches, the subgranular zone (SGZ) in the hippocampus and the subventricular zone (SVZ). While in humans and rodents the SGZ contributes to memory functions by generating new neurons that integrate into hippocampal circuitry, the role of eNPCs of the SVZ is less clear. SVZ-eNPCs contribute to the generation of new neurons fated to the olfactory bulb (OB) in rodents but not in humans where they are thought to contribute to striatal neurogenesis as a result of tissue damage.Here, we show in mice and humans a novel non-neurogenic physiological role of adult SVZ-eNPCs in supporting cognitive functions by regulating striatal neuronal activity. We first provide evidence that GABAergic transmission between parvalbumin-expressing fast-spiking interneurons (FSIs) and medium spiny neurons (MSNs) is tuned by SVZ-eNPCs via secretion of Insulin-Like Growth Factor Binding Protein Like 1 (IGFBPL-1) that, in turn, regulates the Insulin-Like Growth Factor (IGF-1) signalling cascade. Consistently, selective ablation of SVZ-eNPCs and in vivo disruption of the IGF-signalling determine the impairment of intrastriatal coherence. A finding associated with a higher failure rate of GABAergic transmission mediated by FSIs and with striatum-related behavioural dysfunctions impairing decision making. Human validation studies revealed IGFBPL-1 expression in the SVZ and in foetal and induced-pluripotent stem cell-derived NPCs as well as a strong correlation in neurological patients between SVZ pathological damage, reduction of striatum volume and impairment of information processing speed.All in all, our results highlight a novel non-neurogenic homeostatic role exerted by SVZ-eNPCs on striatal GABAergic neurons that might contribute to cognitive processes involving decisions-making tasks.Competing Interest StatementThe authors have declared no competing interest. ER -