{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T10:33:41Z","timestamp":1762079621259},"reference-count":48,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2000,9,1]]},"abstract":"<jats:p> Previous work has shown that seizure-like activity can disrupt the induction of long-term potentiation (LTP). However, how seizure-like event disrupts the LTP induction remains unknown. To understand the cellular and molecular mechanisms underlying this process better, a set of studies was implemented in area CA1 of rat hippocampal slices using extracellular recording methods. We showed here that prior transient seizure-like activity generated by perfused slices with Mg<jats:sup>2+<\/jats:sup>-free artificial cerebrospinal fluid (ACSF) exhibited a persistent suppression of LTP induction. This effect lasted between 2 and 3 h after normal ACSF replacement and was specifically inhibited by N-methyl-d-aspartate (NMDA) receptor antagonistd-2-amino-5-phosphovaleric acid (d-APV) and L-type voltage-operated Ca<jats:sup>2+<\/jats:sup> channel (VOCC) blocker nimodipine, but not by non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). In addition, this suppressive effect was specifically blocked by the selective protein kinase C (PKC) inhibitor NPC-15437. However, neither Ca<jats:sup>2+<\/jats:sup>\/calmodulin-dependent protein kinase II inhibitor KN-62 nor cAMP-dependent protein kinase inhibitor Rp-adenosine 3\u2032,5\u2032-cyclic monophosphothioate (Rp-cAMPS) affected this suppressive effect. This persistent suppression of LTP was not secondary to the long-lasting changes in NMDA receptor activation, because the isolated NMDA receptor\u2013mediated responses did not show a long-term enhancement in response to a 30-min Mg<jats:sup>2+<\/jats:sup>-free ACSF application. Additionally, in prior Mg<jats:sup>2+<\/jats:sup>-free ACSF\u2013treated slices, the entire frequency-response curve of LTP and long-term depression (LTD) is shifted systematically to favor LTD. These results suggest that the increase of Ca<jats:sup>2+<\/jats:sup> influx through NMDA channels and L-type VOCCs in turn triggering a PKC-dependent signaling cascade is a possible cellular basis underlying this seizure-like activity-induced inhibition of LTP. <\/jats:p>","DOI":"10.1152\/jn.2000.84.3.1279","type":"journal-article","created":{"date-parts":[[2017,12,21]],"date-time":"2017-12-21T14:00:42Z","timestamp":1513864842000},"page":"1279-1288","source":"Crossref","is-referenced-by-count":20,"title":["Transient Removal of Extracellular Mg<sup>2+<\/sup> Elicits Persistent Suppression of LTP at Hippocampal CA1 Synapses Via PKC Activation"],"prefix":"10.1152","volume":"84","author":[{"given":"Kuei-Sen","family":"Hsu","sequence":"first","affiliation":[{"name":"Department of Pharmacology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Chia","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Pharmacology 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