TrkB Modulates Fear Learning and Amygdalar Synaptic Plasticity by Specific Docking Sites

• DOI: 10.1523/jneurosci.1707-09.2009
• Publication Date: 2009-08-12T17:28:13Z
• Authors: Gabriele Musumeci; Carla Sciarretta; Antonio Rodríguez...; Mumna Al Banchaab...; Vicente Negrete-Díaz; Marco Costanzi; Valeria Berno; Alexei V. Egorov; Oliver von Bohlen...; Vincenzo Cestari; José M. Delgado-G...; Liliana Minichiello
• Keywords: Neuroscience(all); Conditioning, Classical; Long-Term Potentiation; LONG-TERM POTENTIATION; NEUROTROPHIC FACTOR; NEUROTOXIC LESIONS; LATERAL AMYGDALA; CONDITIONED FEAR; BRAIN; HIPPOCAMPUS; KINASE; MECHANISMS; RESPONSES; In Vitro Techniques; Hippocampus; Mice; 03 medical and health sciences; Memory; Animals; Learning; Point Mutation; Phosphorylation; Maze Learning; 0303 health sciences; Binding Sites; Membrane Glycoproteins; Neuronal Plasticity; Fear; Protein-Tyrosine Kinases; Amygdala; Mice, Mutant Strains; /dk/atira/pure/subjectarea/asjc/2800; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Proto-Oncogene Proteins c-akt

Understanding the modulation of neural circuitry fear is clearly one most important aims in neurobiology. Protein phosphorylation response to external stimuli considered a major mechanism underlying dynamic changes circuitry. TrkB (Ntrk2) neurotrophin receptor tyrosine kinase potently modulates synaptic plasticity and activates signal transduction pathways mainly through two sites [Y515/Shc site; Y816/PLCγ (phospholipase Cγ) site]. To identify molecular required for learning amygdalar downstream TrkB, we used highly defined genetic mouse models carrying single point mutations at these (Y515F or Y816F) examine physiological relevance activated pavlovian conditioning (FC), as well measured by field recordings obtained from neurons different amygdala nuclei. We show that Y816F mutation impairs acquisition FC, plasticity, CaMKII signaling synapses. In contrast, Y515F affects consolidation but not FC tone, also alters AKT signaling. Thus, receptors modulate specific phases main docking sites.