CaltechAUTHORS
  A Caltech Library Service

Enhancement in Motor Learning through Genetic Manipulation of the Lynx1 Gene

Miwa, Julie M. and Walz, Andreas (2012) Enhancement in Motor Learning through Genetic Manipulation of the Lynx1 Gene. PLoS ONE, 7 (11). Art. No. e43302. ISSN 1932-6203. PMCID PMC3489911. doi:10.1371/journal.pone.0043302. https://resolver.caltech.edu/CaltechAUTHORS:20130207-164246258

[img]
Preview
PDF - Published Version
Creative Commons Attribution.

479kB

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20130207-164246258

Abstract

The cholinergic system is a neuromodulatory neurotransmitter system involved in a variety of brain processes, including learning and memory, attention, and motor processes, among others. The influence of nicotinic acetylcholine receptors of the cholinergic system are moderated by lynx proteins, which are GPI-anchored membrane proteins forming tight associations with nicotinic receptors. Previous studies indicate lynx1 inhibits nicotinic receptor function and limits neuronal plasticity. We sought to investigate the mechanism of action of lynx1 on nicotinic receptor function, through the generation of lynx mouse models, expressing a soluble version of lynx and comparing results to the full length overexpression. Using rotarod as a test for motor learning, we found that expressing a secreted variant of lynx leads to motor learning enhancements whereas overexpression of full-length lynx had no effect. Further, adult lynx1KO mice demonstrated comparable motor learning enhancements as the soluble transgenic lines, whereas previously, aged lynx1KO mice showed performance augmentation only with nicotine treatment. From this we conclude the motor learning is more sensitive to loss of lynx function, and that the GPI anchor plays a role in the normal function of the lynx protein. In addition, our data suggests that the lynx gene plays a modulatory role in the brain during aging, and that a soluble version of lynx has potential as a tool for adjusting cholinergic-dependent plasticity and learning mechanisms in the brain.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1371/journal.pone.0043302DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3489911/PubMed CentralArticle
Additional Information:© 2012 Miwa, Walz. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: April 5, 2012; Accepted: July 18, 2012; Published: November 5, 2012. Editor: Jeff A. Beeler, University of Chicago. Funding: This study was supported by the Tobacco-Related Disease Research Program grant TRDRP 19KT-0032 (http://www.trdrp.org/), and Croll Research Foundation on Autism to JMM, and National Institutes of Health, The National Institute of Mental Health grant R43MH083416-02 to AW (http://www.nimh.nih.gov/index.shtml). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: JMM in owns stock Ophidion, Inc. and is an unpaid consultant to the company. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. We would like to thank Jie Xing for technical assistance and Nathaniel Heintz for support. We would also like to acknowledge Pauline Ku, Rell L. Parker and Henry A. Lester for critical reading of the manuscript. Author Contributions: Conceived and designed the experiments: JMM. Performed the experiments: JMM. Analyzed the data: JMM. Contributed reagents/materials/ analysis tools: AW. Wrote the paper: JMM AW.
Funders:
Funding AgencyGrant Number
California Tobacco-Related Disease Research Program19KT-0032
Croll Research Foundation on AutismUNSPECIFIED
NIHR43MH083416-02
Issue or Number:11
PubMed Central ID:PMC3489911
DOI:10.1371/journal.pone.0043302
Record Number:CaltechAUTHORS:20130207-164246258
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20130207-164246258
Official Citation:Miwa JM, Walz A (2012) Enhancement in Motor Learning through Genetic Manipulation of the Lynx1 Gene. PLoS ONE 7(11): e43302. doi:10.1371/journal.pone.0043302
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:36812
Collection:CaltechAUTHORS
Deposited By: Aucoeur Ngo
Deposited On:08 Feb 2013 17:17
Last Modified:09 Nov 2021 23:24

Repository Staff Only: item control page