Regional- and age-dependent reduction in trkB receptor expression in the hippocampus is associated with altered spine morphologies.
BACKGROUND
Changes in densities and in the morphology of dendritic spines in the hippocampus are linked to hippocampal long-term potentiation (LTP), spatial learning, and depression. Decreased brain-derived neurotrophic factor (BDNF) levels seem to contribute to depression. Through its receptor trkB, BDNF is also involved in hippocampal LTP and hippocampus-dependent learning. Conditionally gene-targeted mice in which the ablation of trkB is restricted to the forebrain and occurs only during postnatal development display impaired learning and LTP.


METHODS
To examine whether there is a link among impaired hippocampal synaptic plasticity, altered spines, and trkB receptors, we performed a quantitative analysis of spine densities and spine length in the hippocampal area CA1 and the dentate gyrus in conditional mutant mice (trkB(lox/lox)CaMKII-CRE mice). TrkB protein and mRNA levels were assayed using Western blot and in situ hybridization analysis.


RESULTS
Fifteen-week-old mutant mice exhibit specific reductions in spine densities and a significant increase in spine length of apical and basal dendrites in area CA1. These alterations correlate with a time- and region-specific reduction in full-length trkB mRNA in the hippocampus.


CONCLUSIONS
TrkB functions in structural remodeling of hippocampal dendritic spines, which in turn may affect synaptic transmission and plasticity.
von Bohlen und Halbach
Oliver
O
Department of Neuroanatomy, Interdisciplinary Center for Neurosciences, University of Heidelberg, Heidelberg, Germany. O.von_Bohlen@web.de
Krause
Sonja
S
Medina
Diego
D
Sciarretta
Carla
C
Minichiello
Liliana
L
Unsicker
Klaus
K
D000367:Age Factors; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D049229:Dendritic Spines / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D047468:Immunoprecipitation / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure*; D020813:Receptor, trkB / Q000172:deficiency / Q000378:metabolism*; D016622:Silver Staining / Q000379:methods
D020813:Receptor, trkB