Pyk2 Stabilizes Striatal Medium Spiny Neuron Structure and Striatal-Dependent Action

• Type of Material: Article
• Authors: Shannon Gourley, Emory University; Kolluru D Srikanth, Bar Ilan University; Ellen P Woon, Emory University; Hava Gil-Henn, Bar Ilan University
• Language: English
• Date: 2021-12-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/cells10123442
• Title of Journal or Parent Work: CELLS
• Volume: 10
• Issue: 12
• Grant/Funding Information: This work was supported by NIH MH117103 and DA044297 (to S.L.G.) and The Weisfeld Foundation (to H.G.-H.). The Yerkes National Primate Research Center is supported by N.I.H. OD011132.
• Keywords: PLASTICITY; Life Sciences & Biomedicine; KINASE; CIRCUITS; Pyk2; contingency; learning; INDUCTION; memory; DECISION-MAKING; ORBITOFRONTAL CORTEX; Science & Technology; PATHWAY; FAK; reward; Cell Biology; caudate putamen; SENSITIVITY
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

In day-to-day life, we often choose between pursuing familiar behaviors that have been rewarded in the past or adjusting behaviors when new strategies might be more fruitful. The dorsomedial striatum (DMS) is indispensable for flexibly arbitrating between old and new behavioral strategies. The way in which DMS neurons host stable connections necessary for sustained flexibility is still being defined. An entry point to addressing this question may be the structural scaffolds on DMS neurons that house synaptic connections. We find that the non-receptor tyrosine kinase Proline-rich tyrosine kinase 2 (Pyk2) stabilizes both dendrites and spines on striatal medium spiny neurons, such that Pyk2 loss causes dendrite arbor and spine loss. Viral-mediated Pyk2 silencing in the DMS obstructs the ability of mice to arbitrate between rewarded and non-rewarded behaviors. Meanwhile, the overexpression of Pyk2 or the closely related focal adhesion kinase (FAK) enhances this ability. Finally, experiments using combinatorial viral vector strategies suggest that flexible, Pyk2dependent action involves inputs from the medial prefrontal cortex (mPFC), but not the ventrolateral orbitofrontal cortex (OFC). Thus, Pyk2 stabilizes the striatal medium spiny neuron structure, likely providing substrates for inputs, and supports the capacity of mice to arbitrate between novel and familiar behaviors, including via interactions with the medial-prefrontal cortex.