Regulation of firing of dopaminergic neurons and control of goal-directed behaviors
Abstract
There are several brain regions that have been implicated in the control of motivated behavior and whose disruption leads to the pathophysiology observed in major psychiatric disorders. These systems include the ventral hippocampus, which is involved in context and focus on tasks, the amygdala, which mediates emotional behavior, and the prefrontal cortex, which modulates activity throughout the limbic system to enable behavioral flexibility. Each of these systems has overlapping projections to the nucleus accumbens, where these inputs are integrated under the modulatory influence of dopamine. Here, we provide a systems-oriented approach to interpreting the function of the dopamine system, its modulation of limbic-cortical interactions and how disruptions within this system might underlie the pathophysiology of schizophrenia and drug abuse.
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Dopamine is crucial for communication between the accumbens, amygdala, and prefrontal cortex and signaling between these regions relies upon the fine balance between excitatory and inhibitory dopamine transmission.
“Animal studies have shown that dopamine is crucial for communication between the accumbens, amygdala, and prefrontal cortex and that signaling between these regions relies upon the fine balance between excitatory and inhibitory dopamine transmission (Floresco & Tse 2007; Grace et al. 2007; Jackson et al. 2001).”
From <i>The Adolescent Brain</i> (2008) · cites this paper as Grace et al. 2007
Increased firing of ventral tegmental area dopamine neurons has long been documented in response to rewards and aversive stimuli, and it has been suggested that they increase salience for both types of stimuli.
“increased firing of VTA dopamine neurons has long been documented in response to rewards as well as to aversive stimuli, and it has been suggested that they increase salience for both types of stimuli24, 73–76”
From Neurobiology of resilience (2012) · cites this paper as [75]
ACh released in the VTA promotes the switch between tonic and phasic DAergic activity that signals reward and salience.
“The cholinergic system exerts a profound effect on DAergic activity as ACh released in the VTA promotes the switch between tonic and phasic activity in DAergic neurons that signals reward and salience [38, 39].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [39]
DA neurons in the midbrain project to medium spiny neurons in the NAcc as well as pyramidal neurons in the PFC, thereby modulating firing rates and establishing a strong reciprocal relationship between striatum and PFC.
“DA neurons in the midbrain project to medium spiny neurons in the NAcc as well as pyramidal neurons in the PFC, thereby modulating the firing rates of these neurons and establishing a strong reciprocal relationship between striatum and PFC (Grace, Floresco et al. 2007).”
From Developmental imaging genetics: Linking dopamine function to adolescent behavior (2014) · cites this paper as Grace, Floresco et al. 2007
DA levels are modulated by two dissociable processes of DA discharge that interact: a constant background tonicity and a burst firing high-amplitude phasic release.
“DA levels are modulated by two dissociable processes of DA discharge that interact, (1) a constant background tonicity regulated by baseline firing of DA neurons and glutamatergic afferents from cortical to striatal regions, and (2) a burst firing high-amplitude phasic release (Grace, Floresco et al. 2007).”
From Developmental imaging genetics: Linking dopamine function to adolescent behavior (2014) · cites this paper as Grace, Floresco et al. 2007
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Self-citation
- Authors
- Grace, A. A., Floresco, S. B., Goto, Y., & Lodge, D. J.
- Affiliations
- University of Pittsburgh (US)
- University of British Columbia (CA)
- McGill University (CA)
- Corresponding author
- Grace, Anthony A.
- Venue
- Trends in Neurosciences
- Publisher
- Elsevier BV
- Published
- 2007-05
- Volume
- 30
- Issue
- 5
- Pages
- 220-227
- ISSN
- 0166-2236 (ISSN-L)
- OpenAlex
- W2058578514
- Cited by
- 1,034
- References
- 62
- Citations by year
- 2026: 28 · 2025: 25 · 2024: 37 · 2023: 37 · 2022: 38 · 2021: 49 · 2020: 43 · 2019: 42 · 2018: 59 · 2017: 50 · 2016: 68 · 2015: 80 · 2014: 74 · 2013: 69 · 2012: 70
- FWCI
- 5.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Neurosciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- dopaminergic neurons, dopaminergic system, nucleus accumbens, ventral hippocampus, amygdala, prefrontal cortex, goal-directed behavior, motivated behavior, schizophrenia, drug abuse, mental illness
- MeSH terms
- Animals, Behavior, Behavior, Animal, Brain, Dopamine, Humans, Neural Pathways, Neurons, Reward, Schizophrenia, Substance-Related Disorders
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