Phasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning

By T. Thesen, Chunmao Wang, Orrin Devinsky, Ruben Kuzniecky, W. Doyle, J. Madsen, E. Bromfield, L. Erőss, P. Halász, G. Karmos and 3 more. Science, 2009

1,259 citations recorded by the source corpus.

Rewarding Bursts of Dopamine Dopaminergic neurons are thought to be involved in the cognitive and hedonic underpinnings of motivated behaviors. However, it is still unclear whether dopaminergic neuron activation is sufficient to elicit reward-related behavior and which type of neuronal activity pattern serves this purpose. Tsai et al. (p. 1080; published online 23 April) directly compared tonic versus phasic firing of dopaminergic cells in the ventral tegmental area, and the effects on both behavior and dopamine release. Using a transgenic system and virus injection in mice, they targeted the dopaminergic cells with rhodopsin. Light stimulation was then used to drive dopaminergic cells either with a tonic low level of pulses or bursts of high-frequency pulses, with the number of pulses being equal across conditions. Only the high-frequency phasic firing induced a conditioned place preference and dopamine release. High-frequency pulses in deep brain cells release dopamine and cause reward-related behavior in mice. Natural rewards and drugs of abuse can alter dopamine signaling, and ventral tegmental area (VTA) dopaminergic neurons are known to fire action potentials tonically or phasically under different behavioral conditions. However, without technology to control specific neurons with appropriate temporal precision in freely behaving mammals, the causal role of these action potential patterns in driving behavioral changes has been unclear. We used optogenetic tools to selectively stimulate VTA dopaminergic neuron action potential firing in freely behaving mammals. We found that phasic activation of these neurons was sufficient to drive behavioral conditioning and elicited dopamine transients with magnitudes not achieved by longer, lower-frequency spiking. These results demonstrate that phasic dopaminergic activity is sufficient to mediate mammalian behavioral conditioning.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e17d775c07431ffe44502c02d9dec4005385e1e4

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Citations in the corpus

Flexible near field wireless optoelectronics as subdermal implants for broad applications in optogenetics (2017, positive): “…of these devices in vivo, we targeted the mesolimbic dopaminergic (DA) pathway, a circuit known to facilitate reward and positive reinforcement (Tsai et al., 2009; Witten et al., 2011), by injecting AAV5-DIO-ChR2-eYFP or AAV5-hSynFLEX-ChrimsonR-tdTomato into the ventral tegmental area (VTA) of…”
Linking Molecules to Mood: New Insight Into the Biology of Depression (2010, positive): “Recently developed optogenetic tools make it possible to activate or inhibit particular neuronal cell types, and/or their terminals within defined brain regions (24), allowing for a deeper exploration of the neurophysiological mechanisms underlying the therapeutic effects of DBS.”
FROM REINFORCEMENT LEARNING MODELS OF THE BASAL GANGLIA TO THE PATHOPHYSIOLOGY OF PSYCHIATRIC AND NEUROLOGICAL DISORDERS (2011, background): “Indeed, phasic optogenetic stimulation of dopamine neurons induces a subsequent preference for the place in which such stimulation occurre”
Dopamine signals for reward value and risk: basic and recent data (2010, methodology): “stimulation of dopamine neurons by optogenetic methods via genetically inserted channelrhodopsin induces Pavlovian place preference conditioning in mice [57].”
Principles for applying optogenetic tools derived from direct comparative analysis of microbial opsins (2011, methodology): “To achieve this, we used opsins in a Cre-dependent (double-floxed inverted open reading frame (DIO)) configuratio”
Neuromodulated Spike-Timing-Dependent Plasticity, and Theory of Three-Factor Learning Rules (2016, background): “…electroces is a traditional means to elicit phasic dopamine release, it has now also become possible to to control neuromodulatory signals with optogenetic methods (see e.g., Tsai et al., 2009; Steinberg et al., 2013, for optogenetic activation of phasic dopamine signals in behaving animals).”
Input-specific control of reward and aversion in the ventral tegmental area (2012, positive): “Although VTA DA neurons play a role in reward-dependent behaviors 1-3, 7, 10, 12, 14, 31, 32 and inhibition of VTA DA neurons by GABAergic neurons contributes to reward prediction error calculations and promotes behaviors associated with aversion 10, 12, 13, 15 , the detailed circuits within the…”
Recombinase-driver rat lines: tools, techniques, and optogenetic application to dopamine-mediated reinforcement (2011, positive): “While genetically modified mice have enabled substantial advances in neuroscience and have made possible new approaches for circuit analysis with optogenetics (Tsai et al., 2009; Gradinaru et al., 2009; Lobo et al., 2010; Kravitz et al., 2010; Witten et al., 2010; Tye et al., 2011), a generalizable ”
Circuit Architecture of VTA Dopamine Neurons Revealed by Systematic Input–Output Mapping (2015, background): “VTA-DA and VTA-GABA neurons have distinct firing patterns in vivo (Cohen et al., 2012), and their optogenetic activation produces opposing behavioral effects (Tsai et al., 2009; Tan et al., 2012).”