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Responding to preconditioned cues is devaluation sensitive and requires orbitofrontal cortex during cue-cue learning

  1. Evan E Hart  Is a corresponding author
  2. Melissa J Sharpe
  3. Matthew PH Gardner
  4. Geoffrey Schoenbaum  Is a corresponding author
  1. National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, United States
  2. Department of Psychology, University of California, Los Angeles, United States
  3. Department of Neuroscience, Johns Hopkins School of Medicine, United States
  4. Department of Psychiatry, University of Maryland School of Medicine, United States
  5. Department of Anatomy and Neurobiology, University of Maryland School of Medicine, United States
Research Advance
Cite this article as: eLife 2020;9:e59998 doi: 10.7554/eLife.59998
3 figures and 1 additional file


Task schematic and histology.

(A) Task Schematic. Rats received value-neutral cue pairings during preconditioning. Light was delivered to eYFP control and NpHR rats during cue presentation. Reward conditioning occurred in phase two during which cue B was paired with sucrose pellets and Cue D was presented alone. Cues A and C were probed in phase 3. (B) Schematic reconstruction of fiber tip placements and viral expression in eYFP controls (left) and NpHR rats (right). Light shading indicates areas of minimal spread and dark shading areas of maximal spread. Black circles indicate fiber tip placements. (C) Representative photomicrographs of fiber placements and eYFP expression in lateral OFC.

OFC inhibition during preconditioning impairs value inference during the probe test.

(A) All rats showed low levels of responding during preconditioning when neutral cue pairs were presented. There was no effect of cue or group. (B) During reward conditioning, all rats (grey, eYFP; green, NpHR) showed higher responding to the rewarded cue B (solid lines) than to the non-rewarded cue D (dotted lines). (C) During the probe test, responding to A was higher than to C in control rats (eYFP, left, grey), but not in OFC inhibition rats (NpHR, right, green). (D) Scatter plot of A versus C responding during the probe test. To the extent that responding to A and C are equal, points should congregate along the diagonal. Points below the diagonal indicate A>C responding and therefore evidence of preconditioning.

Responding to preconditioned cues in control rats is outcome devaluation sensitive.

(A) Rats that received LiCl and pellets unpaired (black) showed higher levels of responding to A during the first 2-trial block than rats that received them paired (grey). All rats quickly extinguished. (B) Average responses during the first 2-trial block. (C) Rats that received paired LiCl and pellets (left) consumed fewer pellets than rats that received them unpaired (right) during the consumption test.

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