AUTHOR=Babu Harish , Ramirez Gerardo , Fabel Klaus , Bischofberger Josef , Kempermann Gerd 

TITLE=Synaptic network activity induces neuronal differentiation of adult hippocampal precursor cells through BDNF signaling

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 3 - 2009

YEAR=2009

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/neuro.22.001.2009

DOI=10.3389/neuro.22.001.2009

ISSN=1662-453X

ABSTRACT=Adult hippocampal neurogenesis is regulated by activity. But how do neural precursor cells in the hippocampus respond to surrounding network activity and translate increased neural activity into a developmental program? Here we show that long-term potential (LTP)-like synaptic activity within a cellular network of mature hippocampal neurons promotes neuronal differentiation of newly generated cells. In co-cultures of precursor cells with primary hippocampal neurons, LTP-like synaptic plasticity induced by addition of glycine in Mg2+-free media for 5 min, produced synchronous network activity and subsequently increased synaptic strength between neurons. Furthermore, this synchronous network activity led to a significant increase in neuronal differentiation from the co-cultured neural precursor cells. When applied directly to precursor cells, glycine and Mg2+-free solution did not induce neuronal differentiation. Synaptic plasticity-induced neuronal differentiation of precursor cells was observed in the presence of GABAergic neurotransmission blockers but was dependent on NMDA-mediated Ca2+ influx. Most importantly, neuronal differentiation required the release of brain-derived neurotrophic factor (BDNF) from the underlying substrate hippocampal neurons as well as TrkB receptor phosphorylation in precursor cells. This suggests that activity-dependent stem cell differentiation within the hippocampal network is mediated via synaptically evoked BDNF signaling.