Correlated network activity enhances synaptic efficacy via BDNF and the ERK pathway at immature CA3–CA1 connections in the hippocampus

• DOI: 10.1073/pnas.0704533104
• Publication Date: 2007-07-27T00:55:11Z
• Authors: Majid H. Mohajerani; Sudhir Sivakumaran; Paola Zacchi; Pedro Aguilera; Enrico Cherubini
• Keywords: Schaffer collateral; Postsynaptic density

At early developmental stages, correlated neuronal activity is thought to exert a critical control on functional and structural refinement of synaptic connections. In the hippocampus, between postnatal day 2 (P2) P6, network-driven giant depolarizing potentials (GDPs) are generated by synergistic action glutamate GABA, which excitatory. Here rising phase GDPs was used trigger Schaffer collateral stimulation in such way that synchronized network coincident with presynaptic activation afferent input. This procedure produced persistent increase spontaneous evoked alpha-amino-3-hydroxy-5-methyl-4-isoxadepropionic acid-mediated glutamatergic currents, an effect required calcium influx through postsynaptic L-type channels. No potentiation observed when delay 3 sec introduced stimulation. Pairing-induced prevented scavengers endogenous BDNF or tropomyosin-related kinase receptor B (TrkB) antagonists. Blocking TrkB receptors cell did not prevent effects pairing, suggesting BDNF, possibly secreted from during GDPs, acts localized neurons. Application exogenous mimicked pairing transmission. addition, pairing-induced blocked ERK inhibitors, activates MAPK/ERK cascade, may lead transcriptional regulation new protein synthesis neuron. These results support hypothesis that, period development, GABAA-mediated instrumental tuning excitatory connections provide insights into molecular mechanisms involved this process.