Enhanced cortico-amygdala efficacy and suppressed fear in absence of Rap1.
Auditory fear conditioning, a model for fear learning, is thought to be mediated by synaptic changes in the cortical and thalamic inputs to the lateral amygdala (LA); however, the specific roles of both pathways are still debated. Here, we report that a CaMKII-alpha-Cre-mediated knock-out (KO) of the rap1a and rap1b genes impaired synaptic plasticity and increased basal synaptic transmission in the cortical but not thalamic input to the LA via presynaptic changes: increases in glutamate release probability and the number of glutamate quanta released by a single action potential. Moreover, KO mice with alterations in the cortico-LA pathway had impaired fear learning, which could be rescued by training with a more aversive unconditional stimulus. These results suggest that Rap1-mediated suppression of synaptic transmission enables plasticity in the cortico-amygdala pathway, which is required for fear learning with a moderately aversive unconditional stimulus.
Pan
Bing-Xing
BX
Unit on Behavioral Genetics, Laboratory of Molecular Pathophysiology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
Vautier
Francois
F
Ito
Wataru
W
Bolshakov
Vadim Y
VY
Morozov
Alexei
A
D000679:Amygdala / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000378:metabolism; D002540:Cerebral Cortex / Q000502:physiology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005239:Fear / Q000502:physiology*; D066298:In Vitro Techniques; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009435:Synaptic Transmission / Q000235:genetics; D020668:rap GTP-Binding Proteins / Q000172:deficiency*; D020827:rap1 GTP-Binding Proteins / Q000172:deficiency*
D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; C492136:Rap1b protein, mouse; D020668:rap GTP-Binding Proteins; D020827:rap1 GTP-Binding Proteins