Article

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: 15.05). 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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    • "), (2) CIN activation can drive GABA release from dopaminergic terminals (Nelson et al., 2014; Tritsch et al., 2014) and neuroptide Y-expressing interneurons (English et al., 2011), and (3) their synchronous activation triggers striatal DA release (Threlfell et al., 2012). While we do not know yet how these different actions are coordinated in vivo, these results suggest that DA/ACh interactions are more complex than the traditional antagonistic model would predict. "
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