Diverse subtypes of nicotinic acetylcholine receptors (nAChRs), including fast-desensitizing 7-containing receptors, are expressed in the CNS. While nAChRs appear to regulate cognitive processing and synaptic plasticity, little is known to date about how this regulation occurs, particularly in brain regions known to be important for cognition. By combining patch-clamp electrophysiology with local photolysis of caged carbachol to rapidly activate the 7-containing nAChRs in rat hippocampal CA1 stratum radiatum interneurons in slices, we describe a novel transient up-regulation of channel function. The nAChRs were activated using a paired-pulse uncaging protocol, where the duration of the UV laser pulses (5-25 msec), and the interval between pulses (200 msec to 30 sec), were varied. At relatively long inter-pulse intervals, we observed a strong (> 75%) decrease in the amplitude of the second response due to desensitization. However, when two pulses were applied at a 200 msec interval, a > 3-fold increase in the amplitude of the second response was observed, a phenomenon referred to here as paired-pulse potentiation. Interestingly, this potentiation appeared to be regulated by [Ca²⁺]_i, and/or Ca²⁺-dependent processes, as it was significantly enhanced by dialyzing cells with either the Ca²⁺ chelator BAPTA, or with peptide inhibitors of either calcineurin or PKC, and was attenuated by dialyzing cells with the CaMKII inhibitor KN-93. No potentiation was observed using caged GABA or glutamate, indicating some specificity for nAChRs. Thus, rat hippocampal 7-containing nAChRs possess a newly described phenomenon of paired-pulse potentiation that may be involved in regulating synaptic plasticity in the hippocampus.