Input-specific control of reward and aversion in the ventral tegmental area

By S. Lammel, B. Lim, Chen Ran, Kee Wui Huang, Michael J. Betley, K. Tye, Karl Deisseroth, R. Malenka. 2012

1,236 citations recorded by the source corpus.

Ventral tegmental area (VTA) dopamine neurons have important roles in adaptive and pathological brain functions related to reward and motivation. However, it is unknown whether subpopulations of VTA dopamine neurons participate in distinct circuits that encode different motivational signatures, and whether inputs to the VTA differentially modulate such circuits. Here we show that, because of differences in synaptic connectivity, activation of inputs to the VTA from the laterodorsal tegmentum and the lateral habenula elicit reward and aversion in mice, respectively. Laterodorsal tegmentum neurons preferentially synapse on dopamine neurons projecting to the nucleus accumbens lateral shell, whereas lateral habenula neurons synapse primarily on dopamine neurons projecting to the medial prefrontal cortex as well as on GABAergic (γ-aminobutyric-acid-containing) neurons in the rostromedial tegmental nucleus. These results establish that distinct VTA circuits generate reward and aversion, and thereby provide a new framework for understanding the circuit basis of adaptive and pathological motivated behaviours.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

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Citations in the corpus

Coordinated and Compartmentalized Neuromodulation Shapes Sensory Processing in Drosophila (2015, positive): “Intriguingly, midbrain dopaminergic neurons responsive to punishment and reward also project to distinct targets in the mammalian brain and display a similar functional opponency as a consequence of reciprocal network interactions (Cohen et al., 2012; Lammel et al., 2012, 2014; Lerner et al., 2015).”
Dopamine neurons modulate neural encoding and expression of depression-related behaviour (2012, methodology): “We examined the proportion of NAc neurons ( n 5 123) showing phasic responses to light pulses in VTA or phasic responses associated with FST kicks (Supplementary Figs 17 and 18).”
Neuronal Reward and Decision Signals: From Theories to Data. (2015, background): “Optogenetic activation of tegmental inputs to dopamine neurons projecting to nucleus accumbens elicits place preference, whereas stimulation of habenula inputs to dopamine neurons projecting to frontal cortex induces place dispreference (303).”
Natural neural projection dynamics underlying social behavior. (2014, neutral): “…play distinct roles in modulating reward and aversion based on connectivity to different upstream and downstream structures (Brischoux et al., 2009; Budygin et al., 2012; Chaudhury et al., 2013; Kalivas and Nakamura, 1999; Lammel et al., 2011, 2012; Mirenowicz and Schultz, 1996; Tye et al., 2013).”
Circuit Architecture of VTA Dopamine Neurons Revealed by Systematic Input–Output Mapping (2015, methodology): “which we optically activated individual VTA inputs expressing channelrhodopsin-2 (ChR2) while recording from identified DA neurons projecting to specific targets labeled with retrobeads (Lammel et al., 2012).”
Pain-relief learning in flies, rats, and man: basic research and applied perspectives (2014, background): “This first study on the neural basis of pleasure-attenuated startle suggested that the mesoaccumbal system that is generally crucial for reward-related learning (for reviews, see, e.g., Cardinal and Everitt 2004; Schultz 2013; but see also Bromberg-Martin et al. 2010; Ilango et al. 2012; Lammel et a”