Projection-specific modulation of dopamine neuron synapses by aversive and rewarding stimuli

By S. Lammel, D. Ion, Jochen Roeper, R. Malenka. Neuron, 2011

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SUMMARY Midbrain dopamine (DA) neurons, which play critical roles in learning and motivated behaviors, are not homogeneous but differ in their molecular properties and responses to external stimuli. Here, we examined whether the modulation of excitatory synapses on DA neurons by rewarding or aversive stimuli depends on the respective brain area to which these DA neurons project. We identified specific DA neuron subpopulations in slices following in vivo injection of “Retrobeads” into single target areas of adult mice and found differences in basal excitatory synaptic properties. In vivo administration of cocaine selectively modified excitatory synapses (assayed by AMPAR/NMDAR ratios) on DA cells projecting to nucleus accumbens (NAc) medial shell while an aversive stimulus selectively modified synapses on DA cells projecting to medial prefrontal cortex. In contrast, synapses on DA neurons projecting to NAc lateral shell were modified by both rewarding and aversive stimuli, which presumably reflects saliency. These results suggest that the mesocorticolimbic DA system may be comprised of three anatomically distinct circuits each modified by distinct aspects of motivationally relevant stimuli.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience

View Paper: https://www.semanticscholar.org/paper/ce17b0a36b59cb15ce20f6e59490dc907500e171

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Citations in the corpus

Recombinase-driver rat lines: tools, techniques, and optogenetic application to dopamine-mediated reinforcement (2011, neutral): “Most efforts to target genetically defined subpopulations of neurons in rats have relied on viral strategies (Lawlor et al., 2009; Lee et al., 2010), but since compact promoters are rare and viral vectors have limited packing capacity, published attempts often result in only partial specificity for…”
Dopaminergic modulation of synaptic transmission in cortex and striatum (2012, background): “…can differ significantly with respect to axonal projection areas, electrophysiological properties, and the expression of synthetic enzymes, membrane and vesicular transporters, neuropeptides, and other amino acid transmitters (Bjö rklund and Dunnett, 2007; Hnasko et al., 2010; Lammel et al., 2011).”
Wiring and Molecular Features of Prefrontal Ensembles Representing Distinct Experiences (2016, neutral): “In mPFC, the existing literature does not support or falsify this hypothesis, though mPFC is associated with specific reward and aversion processes (including cocaine-conditioned place preference, (Tzschentke and Schmidt, 1998, 1999), fear and anxiety behaviors (Burgos-Robles et al., 2009; Lammel et”
Whole-brain mapping of direct inputs to midbrain dopamine neurons. (2012, neutral): “For example, VTA dopamine neurons are composed of different subgroups that project to distinct areas, have distinct physiological properties , and involve distinct synaptic plasticity in response to cocaine and pain (Lammel et al., 2008; Lammel et al., 2011).”
Hippocampal replays under the scrutiny of reinforcement learning models. (2018, background): “Such an influence may not necessarily be directly from VTA to HPC, because less coordinated VTA activity with HPC has been reported during sleep than during awake rest (Gomperts et al. 2015), but it could well be through the ventral striatum (VS), which receives both reward signals from the VTA (Lam”
Updating dopamine reward signals (2013, background): “Whereas interest in dopamine reward responses has overshadowed the long known aversive responses, some current work addresses punishment in identifiable groups of dopamine neurons without assessing their incidence relative to reward responsive neurons [32,42].”
Reward and aversion in a heterogeneous midbrain dopamine system (2013, background): “VTA DA neurons projecting to NAc can be subdivided based on their specific projection target (i.e. core versus medial shell versus lateral shell) and these differences may be behaviorally important (Ikemoto, 2007; Lammel et al., 2008, 2011, 2012).”
The mysterious motivational functions of mesolimbic dopamine. (2012, neutral): “For many years, it was thought that ventral tegmental DA neuron activity was not increased by aversive stimuli; however, recent studies have demonstrated that the electrophysiological activity of putative or identified DA neurons is increased by aversive or stressful conditions (Anstrom and Woodward”
Intact-Brain Analyses Reveal Distinct Information Carried by SNc Dopamine Subcircuits (2015, background): “…target-defined subpopulations are located in different subregions of the VTA, their excitatory synapses are differentially modulated by rewarding and aversive stimuli, and they receive distinct inputs, which can elicit opposite behaviors when selectively recruited (Lammel et al., 2008, 2011, 2012).”
Natural neural projection dynamics underlying social behavior. (2014, neutral): “This mPFC projection might instead be relevant in part to behavioral responses of negative valence, as mPFC-projecting VTA DA neurons respond ex vivo to potentially aversion-related stimuli (Lammel et al., 2011).”