{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:22:30Z","timestamp":1791271350272,"version":"4.1.0"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,2,26]]},"abstract":"<jats:p>\n                    The activity-dependent strengthening and weakening of synaptic transmission are hypothesized to be the basis of not only memory and learning but also the refinement of neural circuits during development. Here we report that, in the developing CA1 area of the hippocampus, endocannabinoid (eCB)-mediated heterosynaptic long-term depression (LTD) of glutamatergic excitatory synaptic transmission is associated with PKA-mediated homosynaptic long-term potentiation (LTP). This form of LTD was dominant at postnatal days 2\u201310 (P2\u2013P10), attenuated during development, and finally disappeared in the mature hippocampus. Heterosynaptic LTD of excitatory postsynaptic currents in the developing hippocampus was expressed presynaptically, spread to neighboring neurons, and was mediated by eCBs. Heterosynaptic LTD of field excitatory postsynaptic potentials was associated with a decrease in fiber volley amplitude with a similar time course. Depression of fiber volleys was blocked by K\n                    <jats:sup>+<\/jats:sup>\n                    channel blockers, suggesting the involvement of the decrease in presynaptic excitability in heterosynaptic LTD. In the P2\u2013P5 hippocampus, eCBs also attenuate LTP and fiber volleys in homosynaptic pathways and help to prevent too much excitability in the neonatal hippocampus where the GABAergic system is poorly developed and even excitatory. In the hippocampus older than P6 (P &gt; 6), however, LTP is protected from eCB-mediated depression by PKA activated at presynaptic sites by high-frequency stimulation, serving to highlight PKA-mediated LTP by weakening inactive synapses even in adjacent cells. Thus, eCBs and PKA make synapses plastic without changing excitability homeostasis in the developing hippocampus.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0708349105","type":"journal-article","created":{"date-parts":[[2008,2,19]],"date-time":"2008-02-19T23:33:56Z","timestamp":1203464036000},"page":"3106-3111","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":63,"title":["Regulation of excitability and plasticity by endocannabinoids and PKA in developing hippocampus"],"prefix":"10.1073","volume":"105","author":[{"given":"Hiroki","family":"Yasuda","sequence":"first","affiliation":[{"name":"*Education and Research Center, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi 371-8511, Japan;"},{"name":"Division of Neurophysiology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan;"},{"name":"SORST, Japan Science and Technology Agency, Kawaguchi 442-0012, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Neurophysiology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan;"},{"name":"SORST, Japan Science and Technology Agency, Kawaguchi 442-0012, Japan; and"},{"name":"Brain Science Institute, RIKEN, Wako 351-0198, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadaharu","family":"Tsumoto","sequence":"additional","affiliation":[{"name":"Division of Neurophysiology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan;"},{"name":"SORST, Japan Science and Technology Agency, Kawaguchi 442-0012, Japan; and"},{"name":"Brain Science Institute, RIKEN, Wako 351-0198, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,2,26]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3037696"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(92)90011-3"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5290.1133"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn985"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn920"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/380446a0"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1063545"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00004.2003"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(02)00080-1"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00235-6"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2134-04.2004"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00839"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.01.024"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0309-06.2006"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-10-03864.2002"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4872-05.2006"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn832"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2959-05.2005"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.122149199"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0176-06.2006"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00476-8"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609596104"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703642"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-05-01823.2002"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00375-0"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00695-5"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02913"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-01-00109.2001"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1101\/lm.53303"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(02)00168-5"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M305697200"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5435.1870"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.09.012"},{"key":"e_1_3_3_34_2","first-page":"37.7","article-title":"Transient expression of the CB1 cannabinoid receptor in projection neurons of the embryonic brain.","author":"Vitalis T","year":"2004","unstructured":"T Vitalis, B Berger, J Rossier, Z Lenkei, Transient expression of the CB1 cannabinoid receptor in projection neurons of the embryonic brain. Soc Neurosci, pp. 37.7 (2004).","journal-title":"Soc Neurosci"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0918-04.2004"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2000.83.3.1167"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00372-5"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.05.020"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.29.051605.112834"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(82)91030-7"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409641102"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90056-X"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1137406"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0708349105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T16:36:59Z","timestamp":1649781419000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0708349105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,2,26]]},"references-count":43,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2008,2,26]]}},"alternative-id":["10.1073\/pnas.0708349105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0708349105","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,2,26]]},"assertion":[{"value":"2007-09-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-02-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}