The p75 neurotrophin receptor negatively modulates dendrite complexity and spine density in hippocampal neurons.
The correlation between functional and structural neuronal plasticity is by now well documented. However, the molecular mechanisms translating patterns of neuronal activity into specific changes in the structure of neurons remain unclear. Neurotrophins can be released in an activity-dependent manner, and they are capable of controlling both neuronal morphology and functional synaptic changes. They are thus attractive molecules to be studied in the context of synaptic plasticity. In the CNS, most of the work so far has focused on the role of BDNF and of its tyrosine kinase B receptor (TrkB), but relatively little is known about the function of the pan-neurotrophin receptor p75NTR. In this study, we show in loss-of-function experiments that postnatal hippocampal pyramidal cells in two mutant lines of p75NTR have a higher spine density and greater dendritic complexity than wild-type (WT) mice. Conversely, in a gain-of-function approach, p75NTR overexpression in WT neurons significantly reduces dendritic complexity, as well as spine density in all dendritic compartments. These results show that p75NTR negatively modulates dendritic morphology in adult hippocampal pyramidal neurons and documents a new case of functional antagonism between Trk and p75NTR signaling.
Zagrebelsky
Marta
M
Department of Cellular and Systems Neurobiology, Max Planck Institute of Neurobiology, D-82152 Martinsried, Germany.
Holz
Andreas
A
Dechant
Georg
G
Barde
Yves-Alain
YA
Bonhoeffer
Tobias
T
Korte
Martin
M
D000818:Animals; D000831:Animals, Newborn; D048429:Cell Size; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D049229:Dendritic Spines / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D018014:Gene Transfer Techniques; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D020800:Receptor, Nerve Growth Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013997:Time Factors
D020800:Receptor, Nerve Growth Factor; D049452:Green Fluorescent Proteins; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)