beta 1-Integrins in the Developing Orbitofrontal Cortex Are Necessary for Expectancy Updating in Mice

• Type of Material: Article
• Authors: Lauren M. DePoy, Emory University; Lauren P. Shapiro, Emory University; Henry W. Kietzman, Emory University; Kaitlyn M. Roman, Emory University; Shannon Gourley, Emory University
• Language: English
• Date: 2019-08-21
• Publisher: Society for Neuroscience
• Publication Version: Final Published Version
• Copyright Statement: © 2019 the authors
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1523/JNEUROSCI.3072-18.2019
• Title of Journal or Parent Work: The Journal of Neuroscience
• Volume: 39
• Issue: 34
• Start Page: 6644
• End Page: 6655
• Grant/Funding Information: The Emory Viral Vector and Microscopy Cores are supported by an NINDS Core Facilities grant, P30NS055077.; The Yerkes National Primate Research Center is supported by the Office of Research Infrastructure Programs/OD P51OD011132.; This work was supported by NIH MH101477, MH117103, MH109208, DA034808, the ARCS Foundation, and the Emory Children's Center for Neuroscience Research.
• Keywords: Orbirtal cortex; Cocaine; Expression; Life Sciences & Biomedicine; Synaptic transmission; Neurosciences; orbital; CD29; Medial prefrontal cortex; ARG; Neurosciences & Neurology; extracellular matrix; Science & Technology; Distinct roles; Rat; habit; juvenile; Projections; cell adhesion; Integrin
• Research Categories: Biology, Molecular; Biology, Neuroscience; Psychology, Psychobiology; Health Sciences, Pharmacology

Abstract

Navigating a changing environment requires associating stimuli and actions with their likely outcomes and modifying these associations when they change. These processes involve the orbitofrontal cortex (OFC). Although some molecular mediators have been identified, developmental factors are virtually unknown. We hypothesized that the cell adhesion factor β1-integrin is essential to OFC function, anticipating developmental windows during whichβ1-integrins might be more influential than others.Wediscovered that OFC-selective β1-integrin silencing before adolescence, but not later, impaired the ability of mice to extinguish conditioned fear and select actions based on their likely outcomes. Early-life knock-down also reduced the densities of dendritic spines, the primary sites of excitatory plasticity in the brain, and weakened sensitivity to cortical inputs. Notwithstanding these defects in male mice, females were resilient to OFC (but not hippocampal) β1-integrin loss. Existing literature suggests that resilience may be explained by estradiol-mediated transactivation ofβ1-integrins and tropomyosin receptor kinase B (trkB). Accordingly, we discovered that a trkB agonist administered during adolescence corrected reward-related decision making in β1-integrin-deficient males. In sum, developmental β1-integrins are indispensable for OFC function later in life.