title: Blockade of stimulus convergence in amygdala neurons disrupts taste associative learning.
abstract: Humans and non-human animals learn associations of temporally contingent stimuli to better cope with the changing environment. In animal models of classical conditioning, a neutral conditioned stimulus (CS) predicts an aversive unconditioned stimulus (US). Several lines of indirect evidence indicate that this learning may rely on stimulus convergence in a subset of neurons, but this hypothesis has not been directly tested. In the current study, we tested this hypothesis using a pharmacogenetic approach, the cAMP response element-binding protein (CREB)/Allatostatin Receptor system, to target a subset of amygdala neurons receiving convergent stimuli in mice during conditioned taste aversion. Virally infected basolateral amygdala neurons with higher CREB levels were predominantly active during CS presentation. Blocking stimulus convergence in infected neurons by silencing them during US disrupted taste associative memory. Moreover, silencing infected neurons only during CS also disrupted associative memory formation. These results provide support for the notion that convergent inputs of CS and US in a subpopulation of neurons are critical for associative memory formation.
authors.affiliation: Laboratory of Chemical Pharmacology Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan. lifeasadolphin@gmail.com
authors.forename: Koichi
authors.initials: K
authors.lastname: Hashikawa
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Naka
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakayama
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Rachael
authors.initials: R
authors.lastname: Neve
authors.forename: Norio
authors.initials: N
authors.lastname: Matsuki
mesh_terms: D000679:Amygdala / Q000166:cytology*; D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology*; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D003214:Conditioning, Classical / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D005822:Genetic Vectors / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism; D013649:Taste / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D018013:Receptors, Neuropeptide; C092069:activity regulated cytoskeletal-associated protein; C509142:allatostatin receptor, mouse; C076523:allatostatin; D049452:Green Fluorescent Proteins; D050882:CREB-Binding Protein; C494363:CREBBP protein, human