Deletion of TrkB in adult progenitors alters newborn neuron integration into hippocampal circuits and increases anxiety-like behavior.
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.
Bergami
Matteo
M
Department of Human and General Physiology, University of Bologna, via San Donato 19/2, I-40126 Bologna, Italy.
Rimondini
Roberto
R
Santi
Spartaco
S
Blum
Robert
R
Götz
Magdalena
M
Canossa
Marco
M
D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D020813:Receptor, trkB / Q000235:genetics* / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB