8
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Opposing regulation of dopaminergic activity and exploratory motor behavior by forebrain and brainstem cholinergic circuits

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Dopamine transmission is critical for exploratory motor behavior. A key regulator is acetylcholine: forebrain acetylcholine regulates striatal dopamine release, whereas brainstem cholinergic inputs regulate the transition from tonic to burst firing modes of dopamine neurons. How these sources of cholinergic activity combine to control dopamine efflux and exploratory motor behavior is unclear. Here we show that mice lacking total forebrain acetylcholine exhibit enhanced frequency dependent striatal dopamine release and are hyperactive in a novel environment, whereas mice lacking rostral brainstem acetylcholine are hypoactive. Exploratory motor behavior is normalized by removal of both cholinergic sources. Involvement of dopamine in the exploratory motor phenotypes observed in these mutants is indicated by their altered sensitivity to the dopamine D2 receptor antagonist raclopride. These results support a model in which forebrain and brainstem cholinergic systems act in tandem to regulate striatal dopamine signaling for proper control of motor activity.

          Related collections

          Author and article information

          Journal
          101528555
          37539
          Nat Commun
          Nat Commun
          Nature communications
          2041-1723
          15 February 2017
          2012
          04 March 2017
          : 3
          : 1172
          Affiliations
          [1 ]Department of Neurosurgery and Department of Physiology and Neuroscience, NYU School of Medicine, New York, NY 10016
          [2 ]Smilow Neuroscience Program, NYU School of Medicine, New York, NY 10016
          [3 ]Department of Otolaryngology, NYU School of Medicine, New York, NY 10016
          Author notes
          [* ]Correspondence and requests for materials should be addressed to R.P.M ( robert.machold@ 123456nyumc.org ) or M.E.R. ( margaret.rice@ 123456nyu.edu )
          [#]

          present address: Pediatric Neurology, Centre Hospitalier Universitaire (CHU) Ste-Justine, Montreal, Quebec, Canada

          Article
          PMC5336695 PMC5336695 5336695 nihpa851909
          10.1038/ncomms2144
          5336695
          23132022
          74b4b4bf-1e70-4f51-be2f-72a60f2abd5f
          History
          Categories
          Article

          Comments

          Comment on this article