TrkB modulates fear learning and amygdalar synaptic plasticity by specific docking sites.
Understanding the modulation of the neural circuitry of fear is clearly one of the most important aims in neurobiology. Protein phosphorylation in response to external stimuli is considered a major mechanism underlying dynamic changes in neural circuitry. TrkB (Ntrk2) neurotrophin receptor tyrosine kinase potently modulates synaptic plasticity and activates signal transduction pathways mainly through two phosphorylation sites [Y515/Shc site; Y816/PLCgamma (phospholipase Cgamma) site]. To identify the molecular pathways required for fear learning and amygdalar synaptic plasticity downstream of TrkB, we used highly defined genetic mouse models carrying single point mutations at one of these two sites (Y515F or Y816F) to examine the physiological relevance of pathways activated through these sites for pavlovian fear conditioning (FC), as well as for synaptic plasticity as measured by field recordings obtained from neurons of different amygdala nuclei. We show that a Y816F point mutation impairs acquisition of FC, amygdalar synaptic plasticity, and CaMKII signaling at synapses. In contrast, a Y515F point mutation affects consolidation but not acquisition of FC to tone, and also alters AKT signaling. Thus, TrkB receptors modulate specific phases of fear learning and amygdalar synaptic plasticity through two main phosphorylation docking sites.
Musumeci
Gabriele
G
Mouse Biology Unit, European Molecular Biology Laboratory, Monterotondo, Italy.
Sciarretta
Carla
C
Rodríguez-Moreno
Antonio
A
Al Banchaabouchi
Mumna
M
Negrete-Díaz
Vicente
V
Costanzi
Marco
M
Berno
Valeria
V
Egorov
Alexei V
AV
von Bohlen Und Halbach
Oliver
O
Cestari
Vincenzo
V
Delgado-García
José M
JM
Minichiello
Liliana
L
D000679:Amygdala / Q000502:physiology*; D000818:Animals; D001665:Binding Sites / Q000235:genetics / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D003214:Conditioning, Classical / Q000502:physiology; D005239:Fear; D006624:Hippocampus / Q000502:physiology; D066298:In Vitro Techniques; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology; D018782:Maze Learning / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008568:Memory / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D009473:Neuronal Plasticity / Q000502:physiology*; D010766:Phosphorylation / Q000502:physiology; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D020813:Receptor, trkB
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D008562:Membrane Glycoproteins; D011505:Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; C064371:Ntrk2 protein, mouse; D020813:Receptor, trkB
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