title: Selecting danger signals: dissociable roles of nucleus accumbens shell and core glutamate in predictive fear learning.
abstract: Conditioned stimuli (CSs) vary in their reliability as predictors of danger. Animals must therefore select among CSs those that are appropriate to enter into an association with the aversive unconditioned stimulus (US). The actions of prediction error instruct this stimulus selection so that when prediction error is large, attention to the CS is maintained and learning occurs but when prediction is small attention to the CS is withdrawn and learning is prevented. Here we studied the role of glutamate acting at rat nucleus accumbens shell (AcbSh) and core (AcbC) α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in this selection of danger signals. Using associative blocking and unblocking designs in rats, we show that antagonizing AcbSh AMPA receptors via infusions of 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo[f]quinoxaline-2,3-dione (NBQX; 0.5 μg) prevents the unblocking of fear learning, whereas antagonizing AcbC AMPA receptors via infusions of NBQX (0.5 μg) prevents both the blocking and unblocking of fear learning. These results identify dissociable but complementary roles for AcbSh and AcbC glutamate acting at AMPA receptors in selecting danger signals: AcbSh AMPA receptors upregulate attention and learning to CSs that signal surprising USs, whereas AcbC AMPA receptors encode the predicted outcome of each trial.
authors: School of Psychology, UNSW Australia, Sydney, NSW, Australia.
authors: Susan S Y
authors: SS
authors: Li
authors: School of Psychology, UNSW Australia, Sydney, NSW, Australia.
authors: Gavan P
authors: GP
authors: McNally
mesh_terms: D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005239:Fear; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D018698:Glutamic Acid
keywords: dopamine; pavlovian conditioning; prediction error; surprise