The neurotrophin receptor p75NTR modulates long-term depression and regulates the expression of AMPA receptor subunits in the hippocampus.
Neurotrophins are involved in the modulation of synaptic transmission, including the induction of long-term potentiation (LTP) through the receptor TrkB. Because previous studies have revealed a bidirectional mode of neurotrophin action by virtue of signaling through either the neurotrophin receptor p75NTR or the Trk receptors, we tested the hypothesis that p75NTR is important for longterm depression (LTD) to occur. Although LTP was found to be unaffected in hippocampal slices of two different strains of mice carrying mutations of the p75NTR gene, hippocampal LTD was impaired in both p75NTR-deficient mouse strains. Furthermore, the expression levels of two (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits, GluR2 and GluR3, but not GluR1 or GluR4, were found to be significantly altered in the hippocampus of p75NTR-deficient mice. These results implicate p75NTR in activity-dependent synaptic plasticity and extend the concept of functional antagonism of the neurotrophin signaling system.
Rösch
Harald
H
Department of Cellular and Systems Neurobiology, Max Planck Institute of Neurobiology, D-82152 Martinsried, Germany.
Schweigreiter
Rüdiger
R
Bonhoeffer
Tobias
T
Barde
Yves-Alain
YA
Korte
Martin
M
D000818:Animals; D015153:Blotting, Western; D003863:Depression / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009473:Neuronal Plasticity / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D020800:Receptor, Nerve Growth Factor; D018091:Receptors, AMPA / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D011810:Quinoxalines; D020800:Receptor, Nerve Growth Factor; D018091:Receptors, AMPA; D017475:Receptors, Nerve Growth Factor; C056723:FG 9041; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine