Striatal dopamine release is triggered by synchronized activity in cholinergic interneurons.

Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK.
Neuron (Impact Factor: 15.98). 07/2012; 75(1):58-64. DOI: 10.1016/j.neuron.2012.04.038
Source: PubMed

ABSTRACT Striatal dopamine plays key roles in our normal and pathological goal-directed actions. To understand dopamine function, much attention has focused on how midbrain dopamine neurons modulate their firing patterns. However, we identify a presynaptic mechanism that triggers dopamine release directly, bypassing activity in dopamine neurons. We paired electrophysiological recordings of striatal channelrhodopsin2-expressing cholinergic interneurons with simultaneous detection of dopamine release at carbon-fiber microelectrodes in striatal slices. We reveal that activation of cholinergic interneurons by light flashes that cause only single action potentials in neurons from a small population triggers dopamine release via activation of nicotinic receptors on dopamine axons. This event overrides ascending activity from dopamine neurons and, furthermore, is reproduced by activating ChR2-expressing thalamostriatal inputs, which synchronize cholinergic interneurons in vivo. These findings indicate that synchronized activity in cholinergic interneurons directly generates striatal dopamine signals whose functions will extend beyond those encoded by dopamine neuron activity.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In vivo optogenetics has provided researchers with the ability to delve deeper into the neural basis of behavior by driving cell-type specific circuit connections within and between brain regions. The diverse toolbox available for circuit-and cell-specific manipulations is ever growing. Using these tools in conjunction with established and novel genetic and behavioral methods, neuroscience research has experienced an explosion in the understanding of the roles of specific cell subtypes in behavior. This review aims to outline recent advances in in vivo optogenetic tools for manipulation of behavior related to movement, pain and
    Open Access Animal Physiology 12/2014; 6:33-51. DOI:10.2147/OAAP.S42339
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dystonia is a movement disorder of both genetic and non-genetic causes, which typically results in twisted posturing due to abnormal muscle contraction. Evidence from dystonia patients and animal models of dystonia indicate a crucial role for the striatal cholinergic system in the pathophysiology of dystonia. In this review, we focus on striatal circuitry and the centrality of the acetylcholine system in the function of the basal ganglia in the control of voluntary movement and ultimately clinical manifestion of movement disorders. We consider the impact of cholinergic interneurons (ChIs) on dopamine-acetylcholine interactions and examine new evidence for impairment of ChIs in dysfunction of the motor systems producing dystonic movements, particularly in animal models. We have observed paradoxical excitation of ChIs in the presence of dopamine D2 receptor agonists and impairment of striatal synaptic plasticity in a mouse model of DYT1 dystonia, which are improved by administration of recently developed M1 receptor antagonists. These findings have been confirmed across multiple animal models of DYT1 dystonia and may represent a common endophenotype by which to investigate dystonia induced by other types of genetic and non-genetic causes and to investigate the potential effectiveness of pharmacotherapeutics and other strategies to improve dystonia. Copyright © 2015. Published by Elsevier Ltd.
    Progress in Neurobiology 02/2015; 127-128. DOI:10.1016/j.pneurobio.2015.02.002 · 10.30 Impact Factor
  • Source
    Frontiers in Neural Circuits 03/2015; 9(15). DOI:10.3389/fncir.2015.00015 · 2.95 Impact Factor

Full-text (2 Sources)

Available from
Jun 2, 2014