Cell adhesion presence during adolescence controls the architecture of projection-defined prefrontal cortical neurons and reward-related action strategies later in life

• Type of Material: Article
• Authors: Henry W Kietzman, Emory University; Lauren P Shapiro, Emory University; Gracy Trinoskey-Rice, Emory University; Shannon Gourley, Emory University
• Language: English
• Date: 2022-04-01
• Publisher: ELSEVIER SCI LTD
• Publication Version: Final Published Version
• Copyright Statement: © 2022 The Authors
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.dcn.2022.101097
• Title of Journal or Parent Work: DEVELOPMENTAL COGNITIVE NEUROSCIENCE
• Volume: 54
• Start Page: 101097
• End Page: 101097
• Grant/Funding Information: The work in the S.L.G. lab is supported by NIH T32 GM008602, F30 MH117878, F31 MH109208, R01 MH117103, and P50 MH100023. The Yerkes National Primate Research Center is supported by the Office of Research Infrastructure Programs/OD P51 OD011132. Research reported in this publication was also supported in part by the Emory University Integrated Cellular Imaging Core and Children’s Healthcare of Atlanta.
• Keywords: AXON OUTGROWTH; Neurosciences; Science & Technology; Life Sciences & Biomedicine; Psychology; STABILIZATION; Juvenile; EXCITATORY NEURONS; ARG; ACQUISITION; BASOLATERAL AMYGDALA; mPFC; CORTEX; Habit; Itgb1; DENDRITIC SPINE PATHOLOGY; Psychology, Developmental; CD29; Social Sciences; VULNERABILITY; Neurosciences & Neurology; INTEGRIN
• Research Categories: Health Sciences, Pharmacology

Abstract

Adolescent brain development is characterized by neuronal remodeling in the prefrontal cortex; relationships with behavior are largely undefined. Integrins are cell adhesion factors that link the extracellular matrix with intracellular actin cytoskeleton. We find that β1-integrin presence in the prelimbic prefrontal cortex (PL) during adolescence, but not adulthood, is necessary for mice to select actions based on reward likelihood and value. As such, adult mice that lacked β1-integrin during adolescence failed to modify response strategies when rewards lost value or failed to be delivered. This pattern suggests that β1-integrin-mediated neuronal development is necessary for PL function in adulthood. We next visualized adolescent PL neurons, including those receiving input from the basolateral amygdala (BLA) – thought to signal salience – and projecting to the dorsomedial striatum (DMS) – the striatal output by which the PL controls goal-seeking behavior. Firstly, we found that these projection-defined neurons had a distinct morphology relative to general layer V PL neurons. Secondly, β1-integrin loss triggered the overexpression of stubby-type dendritic spines at the expense of mature spines, including on projection-defined neurons. This phenotype was not observed when β1-integrins were silenced before or after adolescence. Altogether, our experiments localize β1-integrin-mediated cell adhesion within a developing di-synaptic circuit coordinating adaptive action