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  • 1
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Chronic treatment of adult male F-344 rats (9–12 months old) with therapeutically relevant doses of memantine (30 mg/kg/day in chow for 〈8 weeks) increased the maintenance of long-term potentiation of field excitatory postsynaptic potentials from perforant path—granule cell hippocampal synapses recorded in the fascia dentata in vivo. In contrast, there was no effect of memantine on baseline synaptic responses or population spikes. Likewise, short-term exploratory modulation of these hippocampal evoked responses was not different between memantine-treated and control rats. Both groups of rats were able to learn the spatial version of the Morris water task equally well, but the memantine-treated group showed a strong tendency to show more selective spatial search patterns in the training quadrant of the water pool during a final probe trial. As such, these studies provide the first electrophysiological evidence that memantine can increase the durability of synaptic plasticity and provide preclinical confirmation of the cognitive improvement seen with memantine in the treatment of demented patients.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2013
    Keywords: Key words AMPA receptor-mediated EPSCs ; Cyclothiazide ; Hippocampus ; Kinetics ; Long-term potentiation (LTP) ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We have analysed whether the expression of long-term potentiation (LTP) in rat hippocampal CA1 neurons involves a change in the kinetics of (S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated excitatory postsynaptic currents (EPSCs) (AMPA-EPSCs) or their susceptibility to the AMPA receptor modulator cyclothiazide. AMPA-EPSCs in the CA1 region were evoked by alternate stimulation of two independent Schaffer collateral-commissural inputs of slices of adult rat hippocampus. In the current-clamp mode a strong tetanus (100 Hz, 1 s) applied to one input (input I) induced stable LTP of AMPA-EPSCs in this input, while the control input (input II) remained unaffected. For neither input were EPSC rise time and decay kinetics significantly changed. The application of cyclothiazide prolonged the rise time and the decay time constants of the AMPA-EPSCs in both control and potentiated inputs to the same extent (Input I–rise time: 198±8%, decay: 148±12%; input II–rise time: 212±14%, decay: 144±19%; n=8). Furthermore, when present during tetanization cyclothiazide did not occlude LTP, suggesting that cyclothiazide and tetanic stimulation enhance AMPA-EPSCs via independent mechanisms. Our findings argue against changes in (de-)activation or desensitization of AMPA receptors as the molecular basis for the expression of LTP.
    Type of Medium: Electronic Resource
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