PMID- 10777787 OWN - NLM STAT- MEDLINE DCOM- 20000602 LR - 20191023 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 20 IP - 9 DP - 2000 May 1 TI - Brain-derived neurotrophic factor differentially regulates excitatory and inhibitory synaptic transmission in hippocampal cultures. PG - 3221-32 AB - Brain-derived neurotrophic factor (BDNF) has been postulated to be a key signaling molecule in regulating synaptic strength and overall circuit activity. In this context, we have found that BDNF dramatically increases the frequency of spontaneously initiated action potentials in hippocampal neurons in dissociated culture. Using analysis of unitary synaptic transmission and immunocytochemical methods, we determined that chronic treatment with BDNF potentiates both excitatory and inhibitory transmission, but that it does so via different mechanisms. BDNF strengthens excitation primarily by augmenting the amplitude of AMPA receptor-mediated miniature EPSCs (mEPSCs) but enhances inhibition by increasing the frequency of mIPSC and increasing the size of GABAergic synaptic terminals. In contrast to observations in other systems, BDNF-mediated increases in AMPA-receptor mediated mEPSC amplitudes did not require activity, because blocking action potentials with tetrodotoxin for the entire duration of BDNF treatment had no effect on the magnitude of this enhancement. These forms of synaptic regulations appear to be a selective action of BDNF because intrinsic excitability, synapse number, and neuronal survival are not affected in these cultures. Thus, although BDNF induces a net increase in overall circuit activity, this results from potentiation of both excitatory and inhibitory synaptic drive through distinct and selective physiological mechanisms. FAU - Bolton, M M AU - Bolton MM AD - Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA. FAU - Pittman, A J AU - Pittman AJ FAU - Lo, D C AU - Lo DC LA - eng GR - F31 MH011519/MH/NIMH NIH HHS/United States GR - MH11519/MH/NIMH NIH HHS/United States GR - NS32742/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Receptors, GABA-A) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Action Potentials/*drug effects/physiology MH - Animals MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cells, Cultured MH - Hippocampus/*drug effects/physiology MH - Interneurons/drug effects/physiology MH - Neural Inhibition/drug effects/physiology MH - Rats MH - Receptor, trkB/drug effects/physiology MH - Receptors, GABA-A/drug effects/physiology MH - Synaptic Transmission/*drug effects/physiology PMC - PMC6773110 EDAT- 2000/04/25 00:00 MHDA- 2000/06/10 00:00 PMCR- 2000/11/01 CRDT- 2000/04/25 00:00 PHST- 2000/04/25 00:00 [pubmed] PHST- 2000/06/10 00:00 [medline] PHST- 2000/04/25 00:00 [entrez] PHST- 2000/11/01 00:00 [pmc-release] AID - 4098 [pii] AID - 10.1523/JNEUROSCI.20-09-03221.2000 [doi] PST - ppublish SO - J Neurosci. 2000 May 1;20(9):3221-32. doi: 10.1523/JNEUROSCI.20-09-03221.2000.