{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:59:02Z","timestamp":1791179942437,"version":"4.1.0"},"reference-count":64,"publisher":"Society for Neuroscience","issue":"8","license":[{"start":{"date-parts":[[2009,8,25]],"date-time":"2009-08-25T00:00:00Z","timestamp":1251158400000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2009,2,25]]},"abstract":"<jats:p>In the adult rat hippocampus, the axons of granule cells in the dentate gyrus, the mossy fibers (MF), form excitatory glutamatergic synapses with CA3 principal cells. In neonates, MF release into their targets mainly GABA, which at this developmental stage is depolarizing. Here we tested the hypothesis that, at immature MF\u2013CA3 synapses, correlated presynaptic [single fiber-evoked GABA<jats:sub>A<\/jats:sub>-mediated postsynaptic potentials (GPSPs)] and postsynaptic activity (back propagating action potentials) may exert a critical control on synaptic efficacy. This form of plasticity, called spike-timing-dependent plasticity (STDP), is a Hebbian type form of learning extensively studied at the level of glutamatergic synapses. Depending on the relative timing, pairing postsynaptic spiking and single MF-GPSPs induced bidirectional changes in synaptic efficacy. In case of positive pairing, spike-timing-dependent-long-term potentiation (STD-LTP) was associated with a persistent increase in GPSP slope and in the probability of cell firing. The transduction pathway involved a rise of calcium in the postsynaptic cell and the combined activity of cAMP-dependent PKA (protein kinase A) and brain-derived neurotrophic factor (BDNF). Retrograde signaling via BDNF and presynaptic TrkB receptors led to a persistent increase in GABA release. In \u201cpresynaptically\u201d silent neurons, the enhanced probability of GABA release induced by the pairing protocol, unsilenced these synapses. Shifting E<jats:sub>GABA<\/jats:sub>from the depolarizing to the hyperpolarizing direction with bumetanide failed to modify synaptic strength. Thus, STD-LTP of GPSPs provides a reliable way to convey information from granule cells to the CA3 associative network at a time when glutamatergic synapses are still poorly developed.<\/jats:p>","DOI":"10.1523\/jneurosci.5019-08.2009","type":"journal-article","created":{"date-parts":[[2009,2,25]],"date-time":"2009-02-25T18:34:19Z","timestamp":1235586859000},"page":"2637-2647","source":"Crossref","is-referenced-by-count":75,"title":["At Immature Mossy-Fiber\u2013CA3 Synapses, Correlated Presynaptic and Postsynaptic Activity Persistently Enhances GABA Release and Network Excitability via BDNF and cAMP-Dependent PKA"],"prefix":"10.1523","volume":"29","author":[{"given":"Sudhir","family":"Sivakumaran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majid H.","family":"Mohajerani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Cherubini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2009,2,25]]},"reference":[{"key":"2023041303365335000_29.8.2637.1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00351"},{"key":"2023041303365335000_29.8.2637.2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.22.10380"},{"key":"2023041303365335000_29.8.2637.3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2008.06194.x"},{"key":"2023041303365335000_29.8.2637.4","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2887-06.2006"},{"key":"2023041303365335000_29.8.2637.5","doi-asserted-by":"publisher","DOI":"10.1038\/nrn920"},{"key":"2023041303365335000_29.8.2637.6","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00017.2006"},{"key":"2023041303365335000_29.8.2637.7","doi-asserted-by":"crossref","first-page":"10464","DOI":"10.1523\/JNEUROSCI.18-24-10464.1998","article-title":"Synaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type","volume":"18","author":"Bi","year":"1998","journal-title":"J Neurosci"},{"key":"2023041303365335000_29.8.2637.8","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5422.1982"},{"key":"2023041303365335000_29.8.2637.9","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.31.060407.125639"},{"key":"2023041303365335000_29.8.2637.10","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhi083"},{"key":"2023041303365335000_29.8.2637.11","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(91)90003-D"},{"key":"2023041303365335000_29.8.2637.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.09.007"},{"key":"2023041303365335000_29.8.2637.13","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00030.2005"},{"key":"2023041303365335000_29.8.2637.14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.237bu.x"},{"key":"2023041303365335000_29.8.2637.15","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.074930"},{"key":"2023041303365335000_29.8.2637.16","doi-asserted-by":"publisher","DOI":"10.1038\/nature02618"},{"key":"2023041303365335000_29.8.2637.17","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3238-06.2006"},{"key":"2023041303365335000_29.8.2637.18","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19971222)389:3<402::AID-CNE4>3.0.CO;2-4"},{"key":"2023041303365335000_29.8.2637.19","doi-asserted-by":"publisher","DOI":"10.1038\/nm1301"},{"key":"2023041303365335000_29.8.2637.20","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00008-8"},{"key":"2023041303365335000_29.8.2637.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2007.01.002"},{"key":"2023041303365335000_29.8.2637.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.10.025"},{"key":"2023041303365335000_29.8.2637.23","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-3806(01)00288-7"},{"key":"2023041303365335000_29.8.2637.24","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(02)02269-5"},{"key":"2023041303365335000_29.8.2637.25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.219bu.x"},{"key":"2023041303365335000_29.8.2637.26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.170032297"},{"key":"2023041303365335000_29.8.2637.27","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1996.0017"},{"key":"2023041303365335000_29.8.2637.28","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0824-05.2005"},{"key":"2023041303365335000_29.8.2637.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2005.04.005"},{"key":"2023041303365335000_29.8.2637.30","doi-asserted-by":"crossref","first-page":"5594","DOI":"10.1523\/JNEUROSCI.23-13-05594.2003","article-title":"Plasticity of the GABAergic phenotype of the \u201cglutamatergic\u201d granule cells of the rat dentate gyrus","volume":"23","author":"Guti\u00e9rrez","year":"2003","journal-title":"J Neurosci"},{"key":"2023041303365335000_29.8.2637.31","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00551.2006"},{"key":"2023041303365335000_29.8.2637.32","doi-asserted-by":"publisher","DOI":"10.1038\/nn1381"},{"key":"2023041303365335000_29.8.2637.33","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1113\/jphysiol.1993.sp019965","article-title":"Quantal components of unitary EPSCs at the mossy fibre synapse on CA3 pyramidal cells of rat hippocampus","volume":"472","author":"Jonas","year":"1993","journal-title":"J Physiol"},{"key":"2023041303365335000_29.8.2637.34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0305974101"},{"key":"2023041303365335000_29.8.2637.35","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1111\/j.1471-4159.1992.tb10085.x","article-title":"K-252 compounds: modulators of neurotrophin signal transduction","volume":"59","author":"Kn\u00fcsel","year":"1992","journal-title":"J Neurochem"},{"key":"2023041303365335000_29.8.2637.36","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.158550"},{"key":"2023041303365335000_29.8.2637.37","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1673-08.2008"},{"key":"2023041303365335000_29.8.2637.38","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.1993.0088"},{"key":"2023041303365335000_29.8.2637.39","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(94)00116-X"},{"key":"2023041303365335000_29.8.2637.40","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1152\/jn.2000.83.1.359","article-title":"Synaptic GABA(A) activation inhibits AMPA-kainate receptor-mediated bursting in the newborn (P0\u2013P2) rat hippocampus","volume":"83","author":"Lamsa","year":"2000","journal-title":"J Neurophysiol"},{"key":"2023041303365335000_29.8.2637.41","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80265-2"},{"key":"2023041303365335000_29.8.2637.42","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(03)00019-4"},{"key":"2023041303365335000_29.8.2637.43","doi-asserted-by":"crossref","first-page":"10231","DOI":"10.1523\/JNEUROSCI.18-24-10231.1998","article-title":"Enhancement of neurotransmitter release induced by brain-derived neurotrophic factor in cultured hippocampal neurons","volume":"18","author":"Li","year":"1998","journal-title":"J Neurosci"},{"key":"2023041303365335000_29.8.2637.44","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4576-06.2006"},{"key":"2023041303365335000_29.8.2637.45","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5297.209"},{"key":"2023041303365335000_29.8.2637.46","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5435.1870"},{"key":"2023041303365335000_29.8.2637.47","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5297.213"},{"key":"2023041303365335000_29.8.2637.48","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80586-3"},{"key":"2023041303365335000_29.8.2637.49","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.04198.x"},{"key":"2023041303365335000_29.8.2637.50","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0704533104"},{"key":"2023041303365335000_29.8.2637.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2005.07.003"},{"key":"2023041303365335000_29.8.2637.52","doi-asserted-by":"crossref","first-page":"4785","DOI":"10.1523\/JNEUROSCI.17-12-04785.1997","article-title":"GABA activity mediating cytosolic Ca2+ rises in developing neurons is modulated by cAMP-dependent signal transduction","volume":"17","author":"Obrietan","year":"1997","journal-title":"J Neurosci"},{"key":"2023041303365335000_29.8.2637.53","doi-asserted-by":"publisher","DOI":"10.1038\/35049004"},{"key":"2023041303365335000_29.8.2637.54","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4493-05.2006"},{"key":"2023041303365335000_29.8.2637.55","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.23.13304"},{"key":"2023041303365335000_29.8.2637.56","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.107086"},{"key":"2023041303365335000_29.8.2637.57","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1152\/jn.1992.68.1.197","article-title":"Shunting of excitatory input to dentate gyrus granule cells by a depolarizing GABAA receptor-mediated postsynaptic conductance","volume":"68","author":"Staley","year":"1992","journal-title":"J Neurophysiol"},{"key":"2023041303365335000_29.8.2637.58","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1111\/j.1528-1167.2007.01295.x","article-title":"Timing of the developmental switch in GABA(A) mediated signaling from excitation to inhibition in CA3 rat hippocampus using gramicidin perforated patch and extracellular recordings","volume":"48","author":"Tyzio","year":"2007","journal-title":"Epilepsia"},{"key":"2023041303365335000_29.8.2637.59","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0702-07.2007"},{"key":"2023041303365335000_29.8.2637.60","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00245-8"},{"key":"2023041303365335000_29.8.2637.61","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00507-5"},{"key":"2023041303365335000_29.8.2637.62","doi-asserted-by":"publisher","DOI":"10.1038\/nn985"},{"key":"2023041303365335000_29.8.2637.63","doi-asserted-by":"publisher","DOI":"10.1038\/25665"},{"key":"2023041303365335000_29.8.2637.64","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.12.030189.000305"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.5019-08.2009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T19:09:00Z","timestamp":1681412940000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.5019-08.2009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,2,25]]},"references-count":64,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2009,2,25]]},"published-print":{"date-parts":[[2009,2,25]]}},"alternative-id":["10.1523\/JNEUROSCI.5019-08.2009"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.5019-08.2009","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,2,25]]}}}