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 p75(NTR) or the Trk receptors, we tested the hypothesis that p75(NTR) is important for long-term depression (LTD) to occur. Although LTP was found to be unaffected in hippocampal slices of two different strains of mice carrying mutations of the p75(NTR) gene, hippocampal LTD was impaired in both p75(NTR)-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 p75(NTR)-deficient mice. These results implicate p75(NTR) in activity-dependent synaptic plasticity and extend the concept of functional antagonism of the neurotrophin signaling system.