Transgenic mice overexpressing the full-length neurotrophin receptor trkB exhibit increased activation of the trkB-PLCgamma pathway, reduced anxiety, and facilitated learning.
We have investigated the biochemical, physiological, and behavioral properties of transgenic mice overexpressing the full-length neurotrophin receptor trkB (trkB.TK+). The highest trkB.TK+ mRNA overexpression was achieved in the cerebral cortex and hippocampal subfields, both areas also showing strongly increased trkB.TK+ receptor protein expression and phosphorylation. Furthermore, as a result of trkB.TK+ overexpression, partial activation of trkB downstream signaling was observed. Phosphorylation of phospholipaseCgamma-1 was increased but unexpectedly, the expression and phosphorylation levels of signaling molecules Shc and mitogen-activated protein kinase (MAPK) were unaltered. Behavioral studies revealed improved learning and memory in the water maze, contextual fear conditioning, and conditioned taste aversion tests, and reduced anxiety in the elevated plus maze (EPM) and light-dark exploration tests in trkB.TK+ transgenic mice. Electrophysiological studies revealed a reduced long-term potentiation (LTP) at the Schaffer collateral-CA1 synapse in trkB.TK+ mice. Altogether, overexpression of the trkB.TK+ receptor postnatally leads to selective activation of trkB signaling pathways and enhanced learning and memory.
Koponen
Eija
E
Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland.
Võikar
Vootele
V
Riekki
Ruusu
R
Saarelainen
Tommi
T
Rauramaa
Tuomas
T
Rauvala
Heikki
H
Taira
Tomi
T
Castrén
Eero
E
D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism*; D001362:Avoidance Learning / Q000502:physiology; D001923:Brain Chemistry / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D051966:Phospholipase C gamma; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D020813:Receptor, trkB / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics; D010738:Type C Phospholipases / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D020813:Receptor, trkB; D010738:Type C Phospholipases; D051966:Phospholipase C gamma