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The Journal of Neuroscience, October 26, 2005, 25(43):9989-9999; doi:10.1523/JNEUROSCI.2492-05.2005

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Development/Plasticity/Repair
The p75 Neurotrophin Receptor Negatively Modulates Dendrite Complexity and Spine Density in Hippocampal Neurons

Marta Zagrebelsky,¹ Andreas Holz,² Georg Dechant,³ Yves-Alain Barde,⁴ Tobias Bonhoeffer,¹ and Martin Korte¹

Departments of ¹Cellular and Systems Neurobiology and ²Neuroimmunology, Max Planck Institute of Neurobiology, D-82152 Martinsried, Germany, ³Institute for Neuroscience, Innsbruck Medical University, A-6020 Innsbruck, Austria, and ⁴Division of Pharmacology/Neurobiology, Biozentrum, University of Basel, CH-4003 Basel, Switzerland

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 p75^NTR. In this study, we show in loss-of-function experiments that postnatal hippocampal pyramidal cells in two mutant lines of p75^NTR have a higher spine density and greater dendritic complexity than wild-type (WT) mice. Conversely, in a gain-of-function approach, p75^NTR overexpression in WT neurons significantly reduces dendritic complexity, as well as spine density in all dendritic compartments. These results show that p75^NTR negatively modulates dendritic morphology in adult hippocampal pyramidal neurons and documents a new case of functional antagonism between Trk and p75^NTR signaling.

Key words: dendritic morphology; neurotrophin receptors; spine density; hippocampus; pyramidal neurons; p75 neurotrophin receptor

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Received June 17, 2005; revised September 7, 2005; accepted September 8, 2005.

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