Synaptic Network Activity Induces Neuronal Differentiation of Adult Hippocampal Precursor Cells through BDNF Signaling

• Published in: Frontiers in neuroscience Vol. 3; p. 49
• Main Authors: Babu, Harish, Ramirez-Rodriguez, Gerardo, Fabel, Klaus, Bischofberger, Josef, Kempermann, Gerd
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 01.01.2009; Frontiers Media S.A
• Subjects: adult neurogenesis; Brain-derived neurotrophic factor; Calcium influx; Cell differentiation; Cell division; Exercise; Glycine; Hippocampal plasticity; Hippocampus; Kinases; Long-Term Potentiation; Magnesium; N-Methyl-D-aspartic acid; network oscillation; Neurogenesis; Neuroscience; Neurotransmission; neurotrophins; Phosphorylation; precursor cell; Stem cells; Synaptic plasticity; Synaptic strength; TrkB receptors; γ-Aminobutyric acid; Germany; adult neurogenesis; hippocampus; network oscillation; neurotrophins; precursor cell; long-term potentiation
• ISSN: 1662-453X; 1662-4548; 1662-453X
• DOI: 10.3389/neuro.22.001.2009

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 potentiation (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 Mg(2+)-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 Mg(2+)-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 Ca(2+) 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.