β1 Integrins Are Necessary for Medial Prefrontal Cortex Development and Function

Abstract

Proper development and maturation of the brain relies on periods of structural remodeling. These structural adaptations require coordinated signaling between the extracellular environment and the intracellular actin cytoskeleton. Composed of an α subunit responsible for extracellular ligand binding and a β subunit that activates intracellular signaling, integrin receptors provide such a link. Here we tested the hypothesis that the β1 subunit, localized to neuronal synapses and abundant in the mammalian prefrontal cortex, would be essential to prefrontal cortical development, which extends well into adolescence. We used viral‐mediated gene silencing to reduce β1‐integrins in the medial prefrontal cortex (mPFC), delivering viral vectors just prior to the onset of adolescence or in adulthood. Early‐life, but not adult‐onset, β1‐integrin silencing eliminated dendritic spines, the primary sites of excitatory plasticity in the brain. To assess functional consequences, we focused on goal‐directed decision making. The mPFC is necessary for acquiring and consolidating associations between actions and their outcomes, such that mPFC inactivation causes organisms to defer to habitual behavior, which is insensitive to outcomes. We trained mice to nose poke for food reinforcers, then decreased either: 1) the predictive contingency between nose poking and food, or 2) food value. Early‐life β1‐integrin silencing occluded behavioral sensitivity to action‐outcome associations in both conditions, causing habits. Meanwhile, depression‐ and anxiety‐like behaviors were intact. Our findings suggest that developmental β1‐integrins are necessary for mPFC maturation and function.Support or Funding InformationThe work in the SLG lab was supported by NIH F31MH109208 and R01MH117103. The Yerkes National Primate Research Center was supported by the Office of Research Infrastructure Programs/OD P51 OD011132.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.