Excitatory synaptic transmission is depressed in cultured hippocampal neurons of APP/PS1 mice.
One of the strongest anatomical correlates of the degree of clinical impairment in Alzheimer's disease is a decrease in synaptic density. A detailed understanding of the pathophysiological mechanism operating at a synaptic level remains incomplete, in particular whether the pre- or the post-synaptic compartment is initially involved. Here, we studied synaptic transmission in autaptic hippocampal cultures from a double-transgenic mouse model (APPPS1, APP(swe) and PS1(L166P)) and a single-mutant APP transgenic model (APP23, APPswe). APPPS1 neurons revealed significantly reduced amplitudes of evoked AMPA- and NMDA-receptor-mediated excitatory post-synaptic currents, whereas the amplitudes of spontaneous miniature synaptic responses were not altered. The size of the readily releasable synaptic vesicle pool was also decreased, whereas the release probability was not affected. Morphometric immunohistochemical analysis showed a reduction in synaptophysin-positive puncta. In contrast, we did not identify any alterations in synaptic transmission in neurons derived from single APP(swe) transgenic mice. Taken together, our findings suggest that cultured neurons of APPPS1 double-transgenic mice have a significantly reduced number of functional excitatory synapses.
Priller
Christina
C
Zentrum für Neuropathologie und Prionforschung, Ludwig-Maximilians Universität, München, Germany.
Mitteregger
Gerda
G
Paluch
Sandra
S
Vassallo
Neville
N
Staufenbiel
Matthias
M
Kretzschmar
Hans A
HA
Jucker
Mathias
M
Herms
Jochen
J
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D018408:Patch-Clamp Techniques; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism*; D011336:Probability; D058255:Protease Nexins; D018091:Receptors, AMPA / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000235:genetics / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology; D016708:Synaptophysin / Q000378:metabolism
C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D018377:Neurotransmitter Agents; D053764:Presenilin-1; D058255:Protease Nexins; D018091:Receptors, AMPA; D011956:Receptors, Cell Surface; D016194:Receptors, N-Methyl-D-Aspartate; D016708:Synaptophysin