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Author Notes:

E-mail address: shannon.l.gourley@emory.edu

A.J.W., H.W.K., A.M.S., C.G., and S.L.G. designed research; A.J.W., H.W.K., A.M.S., L.M.B., B.R.B., and S.L.G. performed research; A.J.W., H.W.K., A.M.S., B.R.B., and S.L.G. analyzed data; G.J.B. contributed unpublished reagents/analytic tools; A.J.W., H.W.K., C.G., and S.L.G. wrote the paper.

We thank Nisha Raj, John Yamin, Hayley Arrowood, Aylet Allen, and Dr. Kelsey Zimmermann for important contributions.

The authors declare no competing financial interests.

Subjects:

Research Funding:

This work was supported by Children's Healthcare of Atlanta, the Emory Egleston Children's Research Center, NIH MH101477, MH117103, MH103748, GM008602, and GM000680.

The Yerkes National Primate Research Center is supported by the Office of Research Infrastructure Programs/OD P51OD011132.

The Emory Viral Vector Core is supported by an NINDS Core Facilities Grant, P30NS055077.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • Fragile X syndrome
  • habit
  • orbital
  • prefrontal
  • response-outcome
  • stimulus-response
  • MENTAL-RETARDATION PROTEIN
  • LONG-TERM POTENTIATION
  • PREFRONTAL CORTEX
  • ANTERIOR CINGULATE
  • STRUCTURAL PLASTICITY
  • SYNAPTIC PLASTICITY
  • DISTINCT ROLES
  • MEMORY
  • MODEL
  • NEURONS

Reward-Related Expectations Trigger Dendritic Spine Plasticity in the Mouse Ventrolateral Orbitofrontal Cortex

Tools:

Journal Title:

Journal of Neuroscience Nursing

Volume:

Volume 39, Number 23

Publisher:

, Pages 4595-4605

Type of Work:

Article | Final Publisher PDF

Abstract:

An essential aspect of goal-directed decision-making is selecting actions based on anticipated consequences, a process that involves the orbitofrontal cortex (OFC) and potentially, the plasticity of dendritic spines in this region. To investigate this possibility, we trained male and female mice to nose poke for food reinforcers, or we delivered the same number of food reinforcers non-contingently to separate mice. We then decreased the likelihood of reinforcement for trained mice, requiring them to modify action– outcome expectations. In a separate experiment, we blocked action– outcome updating via chemogenetic inactivation of the OFC. In both cases, successfully selecting actions based on their likely consequences was associated with fewer immature, thin-shaped dendritic spines and a greater proportion of mature, mushroom-shaped spines in the ventrolateral OFC. This pattern was distinct from spine loss associated with aging, and we identified no effects on hippocampal CA1 neurons. Given that the OFC is involved in prospective calculations of likely outcomes, even when they are not observable, constraining spinogenesis while preserving mature spines may be important for solidifying durable expectations. To investigate causal relationships, we inhibited the RNA-binding protein fragileXmental retardation protein (encoded by Fmr1), which constrains dendritic spine turnover. Ventrolateral OFC-selective Fmr1 knockdown recapitulated the behavioral effects of inducible OFC inactivation (and lesions; also shown here), impairing action– outcome conditioning, and caused dendritic spine excess. Our findings suggest that a proper balance of dendritic spine plasticity within the OFC is necessary for one’s ability to select actions based on anticipated consequences.

Copyright information:

© 2019 the authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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