 | Figure 1
Nature Neuroscience
2, 271 - 276 (1999)
doi:10.1038/6374
Impaired synaptic plasticity and learning in aged amyloid precursor protein
transgenic micePaul 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 | | | | 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 A (in 10 A 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 s.e., 43 10%, n = 5 slices from 5 mice
for CA1; 28 8%, n = 6/5), whereas aged transgenic slices were
not (14 15%, n = 7/6 for CA1; 0 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 10% for aged controls
and 35 3% for aged transgenics.
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