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Figure 1

Nature Neuroscience  2, 271 - 276 (1999)
doi:10.1038/6374

Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice

Paul F. Chapman, Gail L. White, Matthew W. Jones, Deirdre Cooper-Blacketer, Vanessa J. Marshall, Michael Irizarry, Linda Younkin, Mark A. Good, T. V. P. Bliss, Bradley T. Hyman, Steven G. Younkin & Karen K. Hsiao
 
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Figure 1. Aged APP695SWE mice demonstrate abnormal long-term synaptic plasticity despite otherwise normal synaptic physiology.
(a) Input/output curves generated by stimulating the Schaffer collaterals and recording in CA1 stratum radiatum (left) or by stimulating the perforant pathway and recording in stratum moleculare of the dentate gyrus (right) indicate no significant differences in baseline synaptic responses to low-frequency (0.2 Hz) stimulation. Examples of field EPSPs recorded using extracellular electrodes (top) are taken from single slices at stimulus intensities from 30−100 muA (in 10 muA increments). (b) Following ten minutes of baseline stimulation at 0.067 Hz, tetanic stimulation was delivered to either the Schaffer collateral/commissural pathway (CA1) or to the perforant pathway (dentate gyrus). Theta-burst stimulation was used as tetanus in the Schaffer collaterals; the perforant pathway was tetanized with shorter bursts of higher-frequency stimulation17. Example responses are from 16-month-old control and transgenic mice before (dashed lines) and 50 minutes after tetanic stimulation (solid lines). Although baseline responses were of comparable size, control slices were significantly enhanced in both regions (increase plusminus s.e., 43 plusminus 10%, n = 5 slices from 5 mice for CA1; 28 plusminus 8%, n = 6/5), whereas aged transgenic slices were not (14 plusminus 15%, n = 7/6 for CA1; 0 plusminus 4%, n = 8/4 for dentate gyrus). LTP in CA1 between transgenic mice was no different and controls when tested between two and eight months of age. (c) Paired-pulse facilitation in CA1 did not differ between control and transgenic animals. The fEPSPs illustrated were evoked with an interpulse interval of 30 ms, which on the average produced facilitation of 32 plusminus 10% for aged controls and 35 plusminus 3% for aged transgenics.

 
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