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- Title
Cell Adhesion Factors in the Orbitofrontal Cortex Control Cue-Induced Reinstatement of Cocaine Seeking and Amygdala-Dependent Goal Seeking.
- Authors
Whyte, Alonzo J.; Trinoskey-Rice, Gracy; Davies, Rachel A.; Woon, Ellen P.; Foster, Stephanie L.; Shapiro, Lauren P.; Li, Dan C.; Srikanth, Kolluru D.; Gil-Henn, Hava; Gourley, Shannon L.
- Abstract
Repeated cocaine exposure causes dendritic spine loss in the orbitofrontal cortex, which might contribute to poor orbitofrontal cortical function following drug exposure. One challenge, however, has been verifying links between neuronal structural plasticity and behavior, if any. Here we report that cocaine self-administration triggers the loss of dendritic spines on excitatory neurons in the orbitofrontal cortex of male and female mice (as has been reported in rats). To understand functional consequences, we locally ablated neuronal β1-integrins, cell adhesion receptors that adhere cells to the extracellular matrix and thus support dendritic spine stability. Degradation of β1-integrin tone: (1) caused dendritic spine loss, (2) exaggerated cocaine-seeking responses in a cue-induced reinstatement test, and (3) impaired the ability of mice to integrate new learning into familiar routines, a key function of the orbitofrontal cortex. Stimulating Abl-related gene kinase, overexpressing Prolinerich tyrosine kinase, and inhibiting Rho-associated coiled-coil containing kinase corrected response strategies, uncovering a β1-integrin-mediated signaling axis that controls orbitofrontal cortical function. Finally, use of a combinatorial gene silencing/chemogenetic strategy revealed that β1-integrins support the ability of mice to integrate new information into established behaviors by sustaining orbitofrontal cortical connections with the basolateral amygdala.
- Subjects
DENDRITIC spines; PREFRONTAL cortex; RHO-associated kinases; CELL adhesion; CELL receptors; EXTRACELLULAR matrix; ADAPTOR proteins
- Publication
Journal of Neuroscience, 2021, Vol 41, Issue 27, p5923
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0781-20.2021