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Temporal and septal hippocampal slices were prepared of normal (N) and PTZ\u2010treated (PTZ) adult (\u2265P60) rats, and CA3 field potentials were recorded during perfusion with Mg<jats:sup>2+<\/jats:sup>\u2010free artificial cerebrospinal fluid (ACSF) or with ACSF containing 50\u2003\u03bc<jats:sc>m<\/jats:sc>4\u2010aminopyridine (4\u2010AP).<\/jats:p><jats:p><jats:bold>Key Findings:\u2002<\/jats:bold>In Mg<jats:sup>2+<\/jats:sup>\u2010free ACSF, spontaneous interictal\u2010like epileptiform discharges (IEDs) were recorded in all slices, with significantly higher frequencies in temporal (0.46\u2003\u00b1\u20030.03\u2003Hz, n\u2003=\u200385) versus septal slices (0.20\u2003\u00b1 0.02\u2003Hz, n\u2003=\u200347, p\u2003&lt;\u20030.000001) but no consistent differences in any other group (i.e., male vs. female or N vs. PTZ). The anticholinesterase eserine (10\u2003\u03bc<jats:sc>m<\/jats:sc>) increased their frequencies by 150\u2013200% in N\u2010septal and in all temporal slices and by 300% in PTZ\u2010septal slices (p\u2003=\u20030.0028). In 60% of the slices the excitatory effect persisted throughout drug perfusion, whereas in the remaining ones it was distinguished in two phases: an early \u201ctransient\u201d and a late \u201csteady state.\u201d The steady\u2010state frequencies resembled the predrug ones in N slices but remained significantly elevated in PTZ slices, especially in the septal group. The muscarinic antagonist atropine (1\u2003\u03bc<jats:sc>m<\/jats:sc>) decreased IED frequency in all slices (n\u2003=\u200336, p\u2003=\u20030.005) and also fully reversed the eserine effect (n\u2003=\u200338, p\u2003&lt;\u20030.0001). In 4\u2010AP ACSF, eserine increased spontaneous IED frequency (n\u2003=\u200321) in N and PTZ slices alike; IEDs were subsequently abolished by addition of the NMDA\u2010receptor antagonist D(\u2212)\u20102\u2010amino\u20105\u2010phosphonopentanoic acid (AP5; 50\u2003\u03bc<jats:sc>m<\/jats:sc>, n\u2003=\u20036).<\/jats:p><jats:p><jats:bold>Significance:\u2002<\/jats:bold>These results demonstrate an intrinsic tonic positive muscarinic acetylcholine receptor (mAChR) contribution to the frequency of NMDA receptor\u2013dependent epileptiform discharges that is amplified following an elevation of endogenous ACh and is more pronounced in the septal hippocampus. Moreover, this positive mAChR contribution to the frequency of IEDs is even more pronounced and persistent in the septal extremity after an early life generalized sustained convulsion. This cholinergic enhancement of the excitatory septal hippocampal output may influence cognitive function and performance, and possibly the adult seizure threshold.<\/jats:p>","DOI":"10.1111\/j.1528-1167.2012.03440.x","type":"journal-article","created":{"date-parts":[[2012,3,16]],"date-time":"2012-03-16T20:29:18Z","timestamp":1331929758000},"page":"879-887","source":"Crossref","is-referenced-by-count":21,"title":["Endogenous ACh effects on NMDA\u2010induced interictal\u2010like discharges along the septotemporal hippocampal axis of adult rats and their modulation by an early life generalized seizure"],"prefix":"10.1111","volume":"53","author":[{"given":"Apostolos 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