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.

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Available from: Sarah Threlfell, Apr 28, 2014
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    Neuropharmacology 04/2015; 95. DOI:10.1016/j.neuropharm.2015.03.036 · 4.82 Impact Factor
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    • "remains unknown. This is a critical gap in knowledge especially in light of drug effects directly on dopamine terminals (Lüscher and Ungless, 2006) as well as mechanisms at dopamine terminals that can drive release in a cell body independent manner (Exley and Cragg, 2008; Cachope et al., 2012; Threlfell et al., 2012). Drug-evoked dopamine transients may drive drug-seeking behavior in several ways and transients are known to correlate with operant behaviors to obtain drug (Phillips et al., 2003; Willuhn et al., 2012). "
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    Frontiers in Neural Circuits 09/2014; 8:114. DOI:10.3389/fncir.2014.00114 · 2.95 Impact Factor
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    • "Coincidentally, nicotinic acetylcholine receptor stimulation mediates dopamine release in the rat striatum which is negatively regulated by agonists of adenosine A 2A receptors (Garção et al., 2013). These observations suggest that adenosine A 2A receptors regulate various neurotransmitter systems , and use of specific antagonists of A 2A receptors, therefore, show potential as therapeutic alternatives for PD (Threlfell et al., 2012). "
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