Publisher Correction: Dissociable dopamine dynamics for learning and motivation

Mohebi, Ali; Pettibone, Jeffrey R.; Hamid, Arif; Wong, Jenny Marie T.; Vinson, Leah T.; Patriarchi, Tommaso; Tian, Lin; Kennedy, Robert T.; Berke, Joshua D.

doi:10.1038/s41586-019-1353-6

Cited by 8 publications

(7 citation statements)

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“…In rats from each line we injected a virus (AAV-hSyn-FLEX-ChrimsonR-Tdtomato) into the accumbens core for Cre-dependent expression of the red-shifted opsin Chrimson (Klapoetke et al, 2014; Fig. 3 B , left) followed by a custom optrode (Mohebi et al, 2019). After allowing three weeks for opsin expression, we readily observed light-responsive single units (Fig.…”

Section: Resultsmentioning

confidence: 99%

Knock-In Rat Lines with Cre Recombinase at the Dopamine D1 and Adenosine 2a Receptor Loci

Pettibone

Derman

et al. 2019

eNeuro

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Genetically modified mice have become standard tools in neuroscience research. Our understanding of the basal ganglia in particular has been greatly assisted by BAC mutants with selective transgene expression in striatal neurons forming the direct or indirect pathways. However, for more sophisticated behavioral tasks and larger intracranial implants, rat models are preferred. Furthermore, BAC lines can show variable expression patterns depending upon genomic insertion site. We therefore used CRISPR/Cas9 to generate two novel knock-in rat lines specifically encoding Cre recombinase immediately after the dopamine D1 receptor (Drd1a) or adenosine 2a receptor (Adora2a) loci. Here, we validate these lines using in situ hybridization and viral vector mediated transfection to demonstrate selective, functional Cre expression in the striatal direct and indirect pathways, respectively. We used whole-genome sequencing to confirm the lack of off-target effects and established that both rat lines have normal locomotor activity and learning in simple instrumental and Pavlovian tasks. We expect these new D1-Cre and A2a-Cre rat lines will be widely used to study both normal brain functions and neurological and psychiatric pathophysiology.

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Section: Resultsmentioning

confidence: 99%

Knock-In Rat Lines with Cre Recombinase at the Dopamine D1 and Adenosine 2a Receptor Loci

Pettibone

Derman

et al. 2019

eNeuro

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“…Among the regulation of these neuronal circuits, mesencephalic dopamine system may play a crucial role. The dopamine system plays a critical role in reward prediction [ 3 ], motivational arousal [ 4 ], and responsiveness to conditioned incentive stimuli [ 5 ]. Previous studies indicated that stress could lead to anhedonia in animals [ 28 ] that has been associated with dysfunctions in the reward system, particularly in the dopamine system [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…The ventral tegmental area (VTA) is a major part of the limbic system that plays a pivotal part in reward prediction [ 3 ], motivational arousal [ 4 ], and responsiveness to conditioned incentive stimuli [ 5 ]. The VTA consists of approximately 90% dopaminergic neurons and several γ -aminobutyric acid (GABA) ergic neurons.…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic Reticulum Stress Is Associated with the Mesencephalic Dopaminergic Neuron Injury in Stressed Rats

Niu

Shi

et al. 2021

Analytical Cellular Pathology

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An increasing number of people are in a state of stress due to social and psychological pressures, which may result in mental disorders. Previous studies indicated that mesencephalic dopaminergic neurons are associated with not only reward-related behaviors but also with stress-induced mental disorders. To explore the effect of stress on dopaminergic neuron and potential mechanism, we established stressed rat models of different time durations and observed pathological changes in dopaminergic neurons of the ventral tegmental area (VTA) through HE and thionine staining. Immunohistochemistry coupled with microscopy-based multicolor tissue cytometry (MMTC) was employed to investigate the number changes of dopaminergic neurons. Double immunofluorescence labelling was used to investigate expression changes of endoplasmic reticulum stress (ERS) protein GRP78 and CHOP in dopaminergic neurons. Our results showed that prolonged stress led to pathological alteration in dopaminergic neurons of VTA, such as missing of Nissl bodies and pyknosis in dopaminergic neurons. Immunohistochemistry with MMTC indicated that chronic stress exposure resulted in a significant decrease in dopaminergic neurons. Double immunofluorescence labelling showed that the endoplasmic reticulum stress protein took part in the injury of dopaminergic neurons. Taken together, these results indicated the involvement of ERS in mesencephalic dopaminergic neuron injury induced by stress exposure.

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“…Like other studies, they also found that these populations had different roles in motivating reward behavior. A recent study found that the lateral VTA projections to the NAcc core is specifically involved in generating ongoing motivational behavior [71]. They found that, in general, the VTA DA population encodes reward prediction error, the signal attributed to reinforcement learning.…”

Section: Vta and The Ventral Striatummentioning

confidence: 99%

“…Moreover, as the NAc shell receives more input from the medial VTA, one may infer that the medial VTA to NAc shell circuit is more involved in the process of initial drug acquisition. On the other hand, the lateral VTA projecting to the NAc core has been demonstrated to have a role in ongoing motivation [71]. In addition, not only is the VTA compartmentalized by its medial-lateral axis, but it also has differences along its anterior-posterior axis, especially in terms of its projections.…”

Section: Drug Addiction and Vtamentioning

confidence: 99%

Integrating the Roles of Midbrain Dopamine Circuits in Behavior and Neuropsychiatric Disease

Chen,

Kim

et al. 2021

Biomedicines

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Dopamine (DA) is a behaviorally and clinically diverse neuromodulator that controls CNS function. DA plays major roles in many behaviors including locomotion, learning, habit formation, perception, and memory processing. Reflecting this, DA dysregulation produces a wide variety of cognitive symptoms seen in neuropsychiatric diseases such as Parkinson’s, Schizophrenia, addiction, and Alzheimer’s disease. Here, we review recent advances in the DA systems neuroscience field and explore the advancing hypothesis that DA’s behavioral function is linked to disease deficits in a neural circuit-dependent manner. We survey different brain areas including the basal ganglia’s dorsomedial/dorsolateral striatum, the ventral striatum, the auditory striatum, and the hippocampus in rodent models. Each of these regions have different reported functions and, correspondingly, DA’s reflecting role in each of these regions also has support for being different. We then focus on DA dysregulation states in Parkinson’s disease, addiction, and Alzheimer’s Disease, emphasizing how these afflictions are linked to different DA pathways. We draw upon ideas such as selective vulnerability and region-dependent physiology. These bodies of work suggest that different channels of DA may be dysregulated in different sets of disease. While these are great advances, the fine and definitive segregation of such pathways in behavior and disease remains to be seen. Future studies will be required to define DA’s necessity and contribution to the functional plasticity of different striatal regions.

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Publisher Correction: Dissociable dopamine dynamics for learning and motivation

Abstract: In this Article, during the proofing stage, the extraneous text "RR4" was inadvertently inserted next to the y axis in Fig. 4b. The original Article has been corrected online.

Cited by 8 publications

References 0 publications

Knock-In Rat Lines with Cre Recombinase at the Dopamine D1 and Adenosine 2a Receptor Loci

Knock-In Rat Lines with Cre Recombinase at the Dopamine D1 and Adenosine 2a Receptor Loci

Endoplasmic Reticulum Stress Is Associated with the Mesencephalic Dopaminergic Neuron Injury in Stressed Rats

Integrating the Roles of Midbrain Dopamine Circuits in Behavior and Neuropsychiatric Disease

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