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Bergami, M.* ; Rimondini, R.* ; Santi, S.* ; Blum, R.* ; Götz, M. ; Canossa, M.*

Deletion of TrkB in adult progenitors alters newborn neuron integration into hippocampal circuits and increases anxiety-like behavior.

Proc. Natl. Acad. Sci. U.S.A. 105, 15570-15575 (2008)

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New neurons in the adult dentate gyrus are widely held to incorporate into hippocampal circuitry via a stereotypical sequence of morphological and physiological transitions, yet the molecular control over this process remains unclear. We studied the role of brain-derived neurotrophic factor (BDNF)/TrkB signaling in adult neurogenesis by deleting the full-length TrkB via Cre expression within adult progenitors in TrkB(lox/lox) mice. By 4 weeks after deletion, the growth of dendrites and spines is reduced in adult-born neurons demonstrating that TrkB is required to create the basic organization of synaptic connections. Later, when new neurons normally display facilitated synaptic plasticity and become preferentially recruited into functional networks, lack of TrkB results in impaired neurogenesis-dependent long-term potentiation and cell survival becomes compromised. Because of the specific lack of TrkB signaling in recently generated neurons a remarkably increased anxiety-like behavior was observed in mice carrying the mutation, emphasizing the contribution of adult neurogenesis in regulating mood-related behavior.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords BDNF; LTP; neurogenesis; plasticity; dendritogenesis; GENERATED GRANULE CELLS; ENHANCED SYNAPTIC PLASTICITY; DENTATE GYRUS; NEUROTROPHIC FACTOR; NERVOUS-SYSTEM; NEUROGENESIS; BRAIN; BDNF; DEPRESSION; RAT

ISSN (print) / ISBN 0027-8424

e-ISSN 1091-6490

Journal Proceedings of the National Academy of Sciences of the United States of America

Quellenangaben Volume: 105, Issue: 40, Pages: 15570-15575

Publisher National Academy of Sciences

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Stem Cell Research (ISF)