Midbrain dopamine neurons arbiter OCD-like behavior

Xue, Jinwen; Qian, Dandan; Zhang, Bing-Qian; Yang, Jingxuan; Li, Wei; Bao, Yifei; Qiu, Shi; Fu, Yi; Wang, Shaoli; Yuan, Ti‐Fei; Lu, Wei

doi:10.1073/pnas.2207545119

Cited by 18 publications

(11 citation statements)

References 64 publications

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“…Other motor dysfunctions such as chorea and dystonia have been hypothesised to involve a failure to inhibit unwanted movements in which dopamine dysregulation could be implicated [ 7 ]. Obsessive compulsive disorder (OCD) is thought to involve hyperactivity in parts of the orbito-frontal cortex, and treatments involving dopamine antagonists have been found to augment the benefits of therapies involving serotonin reuptake inhibitors [ 77 ].…”

Section: Discussionmentioning

confidence: 99%

“…A large number of animal models have been developed to investigate the neurological bases for these disorders, many of which have explored genetic, developmental, or drug- or lesion-induced alterations to the dopamine system [ 77 , 78 , 79 , 80 , 81 , 82 ]. Animal studies have also directly explored the role of dopamine in regulating action selection and motivated behaviour [ 83 , 84 , 85 , 86 ].…”

Section: Discussionmentioning

confidence: 99%

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Simulated Dopamine Modulation of a Neurorobotic Model of the Basal Ganglia

Prescott,

Montes González,

Gurney

et al. 2024

Biomimetics

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The vertebrate basal ganglia play an important role in action selection—the resolution of conflicts between alternative motor programs. The effective operation of basal ganglia circuitry is also known to rely on appropriate levels of the neurotransmitter dopamine. We investigated reducing or increasing the tonic level of simulated dopamine in a prior model of the basal ganglia integrated into a robot control architecture engaged in a foraging task inspired by animal behaviour. The main findings were that progressive reductions in the levels of simulated dopamine caused slowed behaviour and, at low levels, an inability to initiate movement. These states were partially relieved by increased salience levels (stronger sensory/motivational input). Conversely, increased simulated dopamine caused distortion of the robot’s motor acts through partially expressed motor activity relating to losing actions. This could also lead to an increased frequency of behaviour switching. Levels of simulated dopamine that were either significantly lower or higher than baseline could cause a loss of behavioural integration, sometimes leaving the robot in a ‘behavioral trap’. That some analogous traits are observed in animals and humans affected by dopamine dysregulation suggests that robotic models could prove useful in understanding the role of dopamine neurotransmission in basal ganglia function and dysfunction.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Simulated Dopamine Modulation of a Neurorobotic Model of the Basal Ganglia

Prescott,

Montes González,

Gurney

et al. 2024

Biomimetics

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“…11,57 Moreover, SNc DA neurons regulate obsessive-like behaviors in ventromedial striatum and lateral orbitofrontal cortex projections via dual gating. 117 Lastly, the Vglut2 + DA neurons in the SNl are implied in the innervation of the amygdala, 90 demonstrating their potential role in affective behaviors.…”

Section: Midbrain Da Neurons and Affective Disordersmentioning

confidence: 99%

Heterogeneity of mesencephalic dopaminergic neurons: From molecular classifications, electrophysiological properties to functional connectivity

Lu,

Xue,

Lai

et al. 2024

The FASEB Journal

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The mesencephalic dopamine (DA) system is composed of neuronal subtypes that are molecularly and functionally distinct, are responsible for specific behaviors, and are closely associated with numerous brain disorders. Existing research has made significant advances in identifying the heterogeneity of mesencephalic DA neurons, which is necessary for understanding their diverse physiological functions and disease susceptibility. Moreover, there is a conflict regarding the electrophysiological properties of the distinct subsets of midbrain DA neurons. This review aimed to elucidate recent developments in the heterogeneity of midbrain DA neurons, including subpopulation categorization, electrophysiological characteristics, and functional connectivity to provide new strategies for accurately identifying distinct subtypes of midbrain DA neurons and investigating the underlying mechanisms of these neurons in various diseases.

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“…Chronic optogenetic activation of the orbitofrontal cortex (OFC) to VMS connection induces an increase in grooming ( Ahmari et al, 2013 ) while enhancing feed-forward inhibition of fast-spiking striatal interneurons driven by lateral OFC optogenetic activation on hyperactive SPNs rescues compulsive behaviors ( Burguière et al, 2013 ). Another recent paper found that optogenetic inhibition of both dSPN-specific SNc projections to the VMS and SNc projections directly to the lateral OFC prevented excessive grooming ( Xue et al, 2022 ).…”

Section: Cellular and Molecular Mechanisms Of Repetitive Behaviormentioning

confidence: 99%

Striatal insights: a cellular and molecular perspective on repetitive behaviors in pathology

Burton,

Longaretti,

Zlatanovic

et al. 2024

Front. Cell. Neurosci.

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Animals often behave repetitively and predictably. These repetitive behaviors can have a component that is learned and ingrained as habits, which can be evolutionarily advantageous as they reduce cognitive load and the expenditure of attentional resources. Repetitive behaviors can also be conscious and deliberate, and may occur in the absence of habit formation, typically when they are a feature of normal development in children, or neuropsychiatric disorders. They can be considered pathological when they interfere with social relationships and daily activities. For instance, people affected by obsessive-compulsive disorder, autism spectrum disorder, Huntington’s disease and Gilles de la Tourette syndrome can display a wide range of symptoms like compulsive, stereotyped and ritualistic behaviors. The striatum nucleus of the basal ganglia is proposed to act as a master regulator of these repetitive behaviors through its circuit connections with sensorimotor, associative, and limbic areas of the cortex. However, the precise mechanisms within the striatum, detailing its compartmental organization, cellular specificity, and the intricacies of its downstream connections, remain an area of active research. In this review, we summarize evidence across multiple scales, including circuit-level, cellular, and molecular dimensions, to elucidate the striatal mechanisms underpinning repetitive behaviors and offer perspectives on the implicated disorders. We consider the close relationship between behavioral output and transcriptional changes, and thereby structural and circuit alterations, including those occurring through epigenetic processes.

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Midbrain dopamine neurons arbiter OCD-like behavior

Cited by 18 publications

References 64 publications

Simulated Dopamine Modulation of a Neurorobotic Model of the Basal Ganglia

Simulated Dopamine Modulation of a Neurorobotic Model of the Basal Ganglia

Heterogeneity of mesencephalic dopaminergic neurons: From molecular classifications, electrophysiological properties to functional connectivity

Striatal insights: a cellular and molecular perspective on repetitive behaviors in pathology

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