Memory is stored in neural networks via changes in synaptic strength mediated in part by NMDA receptor (NMDAR)-dependent long-term potentiation (LTP). Here we show that a cholecystokinin (CCK)-B receptor (CCKBR) antagonist blocks high-frequency stimulation-induced neocortical LTP, whereas local infusion of CCK induces LTP. CCK −/− mice lacked neocortical LTP and showed deficits in a cue-cue associative learning paradigm; and administration of CCK rescued associative learning deficits. Highfrequency stimulation-induced neocortical LTP was completely blocked by either the NMDAR antagonist or the CCKBR antagonist, while application of either NMDA or CCK induced LTP after lowfrequency stimulation. In the presence of CCK, LTP was still induced even after blockade of NMDARs. Local application of NMDA induced the release of CCK in the neocortex. These findings suggest that NMDARs control the release of CCK, which enables neocortical LTP and the formation of cue-cue associative memory. cholecystokinin | NMDA receptor | long-term potentiation | memory | entorhinal cortex M emory is stored in neural networks through changes in synaptic strength (1). Long-term potentiation (LTP) and long-term depression (LTD) are two forms of synaptic plasticity that are believed to represent a neural basis of memory in different brain regions (2-5). The major form of LTP in the hippocampus and neocortex is induced through theta burst stimulation or highfrequency stimulation (HFS) (2, 3). Previous studies have shown that NMDA receptors (NMDARs) play a crucial role in HFSinduced LTP in the hippocampus (6-9) and neocortex (2, 10), and in the formation and consolidation of associative memory (11,12).Serving as the gateway from the hippocampus to the neocortex, the entorhinal cortex forms strong reciprocal connections with the neocortex (13, 14) and shows extensive cholecystokinin (CCK) labeling (15-17) with projections to neocortical areas, including the auditory cortex (13,14,18). CCK is the most abundant cortical neuropeptide (19), and mice lacking the CCK gene exhibit poor performance in a passive avoidance task and display impaired spatial memory (20). Although many studies have focused on GABAergic CCK neurons (21-24), many glutamatergic neurons in the neocortex express CCK (25, 26). We previously found that local infusion of CCK into the auditory cortex of anesthetized rats induces plastic changes that enable auditory cortical neurons to start responding to a light stimulus after its pairing with an auditory stimulus (18). Activation of the entorhinal cortex potentiates neuronal responses in the auditory cortex, and this effect is suppressed by infusion of a CCK-B receptor (CCKBR) antagonist (18), suggesting that the entorhinal cortex enables neocortical plasticity via CCK-containing neurons projecting to the neocortex.If CCK enables cortical neuroplasticity and associative memory formation, then we would expect CCK-induced neuroplasticity to affect LTP. The release of neuropeptides occurs slowly in response to repetitive firing (27,28)....

Chlorhexidine is a chlorinated phenolic disinfectant used commonly in mouthwash for its action against bacteria. However, a comparative study of the action of chlorhexidine on the cell morphology of Gram-positive and Gram-negative bacteria is lacking. In this study, the actions of chlorhexidine on the cell morphology were identified with the aids of electron microscopy. After exposure to chlorhexidine, numerous spots of indentation on the cell wall were found in both Bacillus subtilis and Escherichia coli. The number of indentation spots increased with time of incubation and increasing chlorhexidine concentration. Interestingly, the dented spots found in B. subtilis appeared mainly at the hemispherical caps of the cells, while in E. coli the dented spots were found all over the cells. After being exposed to chlorhexidine for a prolonged period, leakage of cellular contents and subsequent ghost cells were observed, especially from B subtilis. By using 2-D gel/MS-MS analysis, five proteins related to purine nucleoside interconversion and metabolism were preferentially induced in the cell wall of E. coli, while three proteins related to stress response and four others in amino acid biosynthesis were up-regulated in the cell wall materials of B. subtilis. The localized morphological damages together with the biochemical and protein analysis of the chlorhexidine-treated cells suggest that chlorhexidine may act on the differentially distributed lipids in the cell membranes/wall of B. subtilis and E. coli.

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