{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:37:42Z","timestamp":1791052662957,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,11,2]],"date-time":"2005-11-02T00:00:00Z","timestamp":1130889600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2005,11]]},"abstract":"<jats:p>GABA<jats:sub>B<\/jats:sub> receptor (GABA<jats:sub>B<\/jats:sub>R)\u2010mediated presynaptic inhibition regulates neurotransmitter release from synaptic terminals. In the neonatal hippocampus, GABA<jats:sub>B<\/jats:sub>R activation reduces GABA release and terminates spontaneous network discharges called giant depolarizing potentials (GDPs). Blocking GABA<jats:sub>B<\/jats:sub>Rs transforms GDPs into longer epileptiform discharges. Thus, GABA<jats:sub>B<\/jats:sub>R\u2010mediated presynaptic inhibition of GABA release (GABA auto\u2010inhibition) controls both spontaneous network activity and excitability in the developing hippocampus. Here we show that extensive release of endogenous GABA during epileptiform activity impairs GABA auto\u2010inhibition, but not GABA<jats:sub>B<\/jats:sub>R\u2010mediated inhibition of glutamate release, leading to hyperexcitability of the neonatal hippocampal network. Paired\u2010pulse depression of GABA release (PPD) and heterosynaptic depression of glutamate release were used to monitor the efficacy of presynaptic GABA<jats:sub>B<\/jats:sub>R\u2010mediated inhibition in slices. PPD, but not heterosynaptic depression, was dramatically reduced after potassium (K<jats:sup>+<\/jats:sup>)\u2010induced ictal\u2010like discharges (ILDs), suggesting a selective impairment of GABA<jats:sub>B<\/jats:sub>R\u2010dependent presynaptic inhibition of GABAergic terminals. Impairing GABA auto\u2010inhibition induced a 44% increase in GDP width and the appearance of pathological network discharges. Preventing GABA\u2010induced activation of GABA<jats:sub>B<\/jats:sub>Rs during ILDs avoided PPD loss and most modifications of the network activity. In contrast, a partial block of GABA<jats:sub>B<\/jats:sub>Rs induced network discharges strikingly similar to those observed after K<jats:sup>+<\/jats:sup>\u2010driven ILDs. Finally, neither loss of GABA auto\u2010inhibition nor network hyperexcitability could be observed following synchronous release of endogenous GABA in physiological conditions (during GDPs at 1 Hz). Thus, epileptiform activity was instrumental to impair GABA<jats:sub>B<\/jats:sub>R\u2010dependent presynaptic inhibition of GABAergic terminals. In conclusion, our results indicate that endogenous GABA released during epileptiform activity can reduce GABA auto\u2010inhibition and trigger pathological network discharges in the newborn rat hippocampus. Such functional impairment may play a role in acute post\u2010seizure plasticity.<\/jats:p>","DOI":"10.1113\/jphysiol.2005.094631","type":"journal-article","created":{"date-parts":[[2005,8,12]],"date-time":"2005-08-12T00:55:24Z","timestamp":1123808124000},"page":"951-966","source":"Crossref","is-referenced-by-count":9,"title":["Epileptiform activity triggers long\u2010term plasticity of GABA<sub>B<\/sub> receptor signalling in the developing rat hippocampus"],"prefix":"10.1113","volume":"568","author":[{"given":"P.","family":"Tosetti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Ferrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. Colin\u2010Le","family":"Brun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. L.","family":"Ga\u00efarsa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,11,2]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00064a005"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1989.sp017762"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1988.sp017294"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(97)01147-8"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-17-06826.2003"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(98)80059-7"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00036.2003"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5247.369"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(98)80058-5"},{"key":"e_1_2_5_11_1","doi-asserted-by":"crossref","first-page":"11382","DOI":"10.1523\/JNEUROSCI.23-36-11382.2003","article-title":"Plasticity of GABA(B) receptor\u2013mediated heterosynaptic interactions at mossy fibers after status epilepticus","volume":"23","author":"Chandler KE","year":"2003","journal-title":"J Neurosci"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/11330"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(91)90003-D"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn833"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1990.sp018080"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-05-01840.2003"},{"key":"e_1_2_5_17_1","first-page":"157","article-title":"Inhibitory mechanisms of epileptic seizure generation","volume":"67","author":"Engel J","year":"1995","journal-title":"Adv Neurol"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(98)00107-6"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.21.8501"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(03)00102-7"},{"key":"e_1_2_5_21_1","doi-asserted-by":"crossref","first-page":"4250","DOI":"10.1523\/JNEUROSCI.16-13-04250.1996","article-title":"Kainic acid\u2010induced seizures enhance dentate gyrus inhibition by downregulation of GABAB receptors","volume":"16","author":"Haas KZ","year":"1996","journal-title":"J Neuroscience"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80642-X"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410440602"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1088\/1741-2560\/4\/2\/001"},{"key":"e_1_2_5_25_1","doi-asserted-by":"crossref","first-page":"7662","DOI":"10.1523\/JNEUROSCI.17-20-07662.1997","article-title":"Long\u2010lasting GABA\u2010mediated depolarization evoked by high\u2010frequency stimulation in pyramidal neurons of rat hippocampal slice is attributable to a network\u2010driven, bicarbonate\u2010dependent K+ transient","volume":"17","author":"Kaila K","year":"1997","journal-title":"J Neuroscience"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80956-3"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1125"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1997.sp021900"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-18-06820.2000"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(01)02350-3"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1996.76.2.1036"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1996.76.2.1282"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2004.03.009"},{"key":"e_1_2_5_34_1","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1152\/jn.1999.82.2.638","article-title":"GABAB receptor activation promotes seizure activity in the juvenile rat hippocampus","volume":"82","author":"Motalli R","year":"1999","journal-title":"J Neurophysiol"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.2001.0995"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1994.72.6.2911"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1985.54.5.1363"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00345-2"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7638623"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2003.02964.x"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1998.00351.x"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0953-816X.2004.03413.x"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(00)00096-9"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1999.00837.x"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200006)47:6<729::AID-ANA5>3.0.CO;2-C"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-04-01248.2002"},{"key":"e_1_2_5_47_1","doi-asserted-by":"crossref","first-page":"9261","DOI":"10.1523\/JNEUROSCI.17-23-09261.1997","article-title":"Partial hippocampal kindling decreases efficacy of presynaptic GABAB autoreceptors in CA1","volume":"17","author":"Wu C","year":"1997","journal-title":"J Neurosci"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.2005.094631","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.2005.094631","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T10:20:00Z","timestamp":1697019600000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.2005.094631"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,11]]},"references-count":46,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2005,11]]}},"alternative-id":["10.1113\/jphysiol.2005.094631"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.2005.094631","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,11]]}}}