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


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
    • "The photostimulation diameter through the objective lens is approximately 400 μm with an illumination intensity of 9 mW/mm 2 . Other modes of photostimulation include coupling of fiber optic to the microscope and stimulation using laser, as described in [90] , or a TTL controlled shutter of the fluorescent light source, as described in [92]. "
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    ABSTRACT: The striatum is the principal input structure of the basal ganglia, comprised almost entirely of inhibitory neurons, which include projection neurons and a small yet diverse population of interneurons. Striatal afferents include glutamatergic inputs from the neocortex and thalamus, and massive dopaminergic input from the substantia nigra pars compacta. In order to better understand the operational roles of striatum, it is essential to have a good grasp of its microcircuitry, namely a detailed description of its neuron types and their synaptic connectivity. Traditionally, studying synaptic connectivity between identified neurons was performed using paired and multineuron intracellular recordings in brain slices. The recent introduction of optogenetic methods offers new experimental approaches for microcircuit analysis, one of which is the combination of whole-cell patch-clamp recordings and optogenetic activation of presynaptic neurons. In this chapter we present recent advances in our understanding of the striatal microcircuitry when studied with electrophysiological and optogenetic methods. We first introduce the different neuron types comprising the striatal microcircuitry and describe their basic interconnectivity as inferred from electrophysiological measurements.We then present a few recent studies performed primarily in striatal and corticostriatal slices, where the powerful combination of electrophysiology and optogenetics revised our understanding of striatal functional organization.
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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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    • "Stimulation of dopamine D1 receptors prolongs striatal membrane depolarizations (Hern andez-L opez et al., 1997), which may underlie the immediate focusing effect of dopamine on behavior. Thus, the synaptic dopamine actions, despite their heterogeneity (Threlfell et al., 2012: Roeper, 2013; Chuhma et al., 2014), are overall consistent with the behavioral dopamine functions in learning and approach. "
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