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To test this hypothesis, we augmented extracellular buffering in mouse hippocampal slices by adding 2 \u03bc<jats:sc>m<\/jats:sc>bovine type II carbonic anhydrase to the superfusate. With addition of enzyme, the alkaline transient elicited by a 10 pulse, 100 Hz stimulus train was reduced by 33%. At a holding potential (<jats:italic>V<\/jats:italic><jats:sub>H<\/jats:sub>) of \u221230 mV, the enzyme decreased the half-time of decay and charge transfer of EPSCs by 32 and 39%, respectively, but had no effect at a<jats:italic>V<\/jats:italic><jats:sub>H<\/jats:sub>of \u221280 mV. In current clamp, a 10 pulse, 100 Hz stimulus train gave rise to an NMDAR-dependent afterdepolarization (ADP). Exogenous enzyme curtailed the ADP half-width and voltage integral by 20 and 25%, respectively. Similar reduction of the ADP was noted with a brief 12 Hz stimulus train. The effect persisted in the presence of GABAergic antagonists or the L-type Ca<jats:sup>2+<\/jats:sup>channel blocker methoxyverapamil hydrochloride but was absent in the presence of the carbonic anhydrase inhibitor benzolamide or when the exogenous enzyme was heat inactivated. The effects of the enzyme in voltage and current clamp were noted in 0 Mg<jats:sup>2+<\/jats:sup>media but were abolished when (+)-5-methyl-10,11-dihydro-5<jats:italic>H<\/jats:italic>-dibenzo[a,d]-cyclohepten-5,10-imine maleate was included in the patch pipette. These results provide strong evidence that endogenous alkaline transients are sufficiently large in the vicinity of the synapse to augment NMDAR responses.<\/jats:p>","DOI":"10.1523\/jneurosci.2304-07.2007","type":"journal-article","created":{"date-parts":[[2007,7,11]],"date-time":"2007-07-11T19:13:45Z","timestamp":1184181225000},"page":"7438-7446","source":"Crossref","is-referenced-by-count":48,"title":["Endogenous Alkaline Transients Boost Postsynaptic NMDA Receptor Responses in Hippocampal CA1 Pyramidal 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