Dopamine neurons of the ventral tegmental area (VTA) have been theorized to play a part in various aspects of motivated behaviour
These different behaviours may be mediated by different dopamine neurons interacting with specific neuronal networks
The outputs of VTA neurons are integrated not only with inputs from several brain structures but also with those from local VTA GABA and glutamate neurons (forming a microcircuitry)
Emerging evidence indicates that subpopulations of VTA GABA and glutamate neurons receive afferents from and project to the same brain regions that are connected to VTA dopamine neurons
The VTA contains subpopulations of combinatorial neurons that co-release either glutamate or GABA with dopamine, as well as glutamate neurons that co-release GABA
Optogenetic approaches in transgenic rodents have revealed discrete VTA neuronal phenotypes and connections that have distinct roles in reinforcement, motivation and learning
Dopamine-releasing neurons of the ventral tegmental area (VTA) have central roles in reward-related and goal-directed behaviours. VTA dopamine-releasing neurons are heterogeneous in their afferent and efferent connectivity and, in some cases, release GABA or glutamate in addition to dopamine. Recent findings show that motivational signals arising from the VTA can also be carried by non-dopamine-releasing projection neurons, which have their own specific connectivity. Both dopamine-releasing and non-dopamine-releasing VTA neurons integrate afferent signals with local inhibitory or excitatory inputs to generate particular output firing patterns. Various individual inputs, outputs and local connections have been shown to be sufficient to generate reward- or aversion-related behaviour, indicative of the impressive contribution of this small population of neurons to behaviour.
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The authors thank D. Root, D. Barker, C. Mejias-Aponte, H.-L. Wang and Z. Shiliang for constructive criticism of the initial manuscript. Work on this article was supported by the Intramural Research Program (IRP) of the National Institute on Drug Abuse (IRP/NIDA/NIH) to M.M. and by the National Institute on Drug Abuse Award R01 DA030529 to E.B.M.
The authors declare no competing financial interests.
- Incentive salience
A psychological process through which a stimulus is conferred with motivational properties that make it more attractive or 'wanted'.
- Stimulus salience
The extent to which a thing or an event stands out from the rest.
- Motivated behaviour
An action that is driven by internal states such as desire or hunger.
- Asymmetric synapses
Synaptic contacts that are observed via electron microscopy in which the postsynaptic thickening is wider than the presynaptic one. They are thought to comprise largely excitatory connections. The thickening indicates the high density of proteins that are involved in glutamatergic neurotransmission and plasticity.
- Axonal microdomains
Compartments along the axon with dimensions on the order of microns that share similar properties (such as specific vesicles or biochemical markers). In this article, we use this term specifically to refer to microdomains within terminal regions.
- Medium spiny neurons
(MSNs). Principal projection neurons of the nucleus accumbens and dorsal striatum. These neurons release GABA and comprise >95% of the neurons in these regions.
- Proteasomal degradation
Enzymatic breakdown of proteins by protein complexes (proteasomes) in which the small protein ubiquitin is conjugated to proteins that are destined for degradation.
- Volume transmission
A form of neurotransmission in which a neurotransmitter or modulator is released into the extrasynaptic space such that it diffuses away from the release site to activate receptors with broader distribution beyond a single synapse.
- Conditioned placed preference
A Pavlovian behavioural paradigm during which a subject learns to associate a particular manipulation, such as a drug administration or optogenetic stimulation, with a specific physical environment (a second environment is associated with a control manipulation). On a subsequent testing day in which no manipulation is administered, the subject can freely move between the two training environments: when a subject chooses to spend more time in the environment that is paired with the active manipulation, the interpretation is that the subject found the manipulation 'rewarding'.
- Conditioned place aversion
When the same behavioural conditioning as in conditioned place preference results in the subject avoiding the environment that is associated with the active manipulation, it is interpreted as an 'aversive' manipulation.
- Optical intracranial self-stimulation
A behavioural paradigm in which animals work (for example, press a lever or roll a cylinder with their paws) to deliver light to a brain region where a light sensitive channel, such as channelrhodopsin 2, is present.
- Instrumental behaviour
A behavioural paradigm in which a particular behavioural response is associated with an outcome. It is goal directed insofar as the action increases the likelihood of obtaining rewards or avoiding punishments. Instrumental behaviour is distinguished from Pavlovian (classical) conditioning, in which stimulus and outcome are associated but no response action is required.
- Perseverative behaviour
An inability to update or alter a behavioural strategy when the rule (or rules) of the current task has changed, leading to suboptimal performance.
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Morales, M., Margolis, E. Ventral tegmental area: cellular heterogeneity, connectivity and behaviour. Nat Rev Neurosci 18, 73–85 (2017). https://doi.org/10.1038/nrn.2016.165
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