NF1 dissociates cell type specific contributions toward reward valuation and motor control

Abstract

Neurofibromin 1 (NF1) is a large multidomain signaling molecule that is a major Ras regulator but also acts as a positive regulator of cAMP levels by mediating G protein‐coupled receptor (GPCR)‐dependent activation of adenylate cyclase. Mutations in the NF1 gene cause Neurofibromatosis type 1, a genetic disorder characterized by multiple benign and malignant tumors with prominent neuropsychiatric symptoms that include learning and attention deficits, as well as motor impairments. Recently, we found that NF1 is a direct effector of GPCR signaling via Gβγ subunits in the striatum. However, it remains unclear the signaling contribution of NF1 in striatal‐mediator behaviors. Here we demonstrate the impact of intracellular signaling pathways commonly targeted by neurotransmitter inputs that impact medium spiny neurons (MSN) activity can be dissociated in a cell‐specific manner with distinct contribution to motor learning and reward‐related behaviors. We genetically ablated NF1 with cellular resolution demonstrating the diverging behavioral and signaling specific manner in which NF1 contributes to the acquisition and consolidating of learning a motor skill, as well as its regulation of morphine reward.Support or Funding InformationThis work was supported by the NIH and by the Canadian Institutes of Health Research (CIHR) Fellowship.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.