scholarly journals Retrograde labeling illuminates distinct topographical organization of D1 and D2 receptor-positive neurons in the prefrontal cortex of mice

2020 ◽  
Author(s):  
Sara M. Green ◽  
Sanya Nathani ◽  
Joseph Zimmerman ◽  
David Fireman ◽  
Nikhil M. Urs
Keyword(s):  
Prefrontal Cortex ◽  
Dopamine Receptor ◽  
Pyramidal Neurons ◽  
D2 Receptor ◽  
Dorsal Striatum ◽  
Behavioral Flexibility ◽  
Substantia Nigra Pars Compacta ◽  
Projection Neurons ◽  
D1 And D2 Receptors ◽  
Topographical Organization

ABSTRACTThe cortex plays an important role in regulating motivation and cognition, and does so by regulating multiple subcortical brain circuits. Glutamatergic pyramidal neurons in the prefrontal cortex (PFC) are topographically organized in different subregions such as the prelimbic, infralimbic and orbitofrontal, and project to topographically-organized subcortical target regions. Dopamine D1 and D2 receptors are expressed on glutamatergic pyramidal neurons in the PFC. However, it is unclear whether D1 and D2 receptor-expressing pyramidal neurons in the PFC are also topographically organized. We used a retrograde adeno-associated virus (AAVRG)-based approach to illuminate the topographical organization of D1 and D2 receptor-expressing neurons, projecting to distinct striatal and midbrain subregions. Our experiments reveal that AAVRG injection in the nucleus accumbens (NAcc) or dorsal striatum (dSTR) of D1Cre mice labeled distinct neuronal subpopulations in medial orbitofrontal or prelimbic PFC, respectively. However, AAVRG injection in NAcc or dSTR of D2Cre mice labeled medial orbitofrontal, but not medial prelimbic PFC, respectively. Additionally, D2R+ but not D1R+ PFC neurons were labeled upon injection of AAVRG in substantia nigra pars compacta (SNpc). Thus, our data are the first to highlight a unique dopamine receptor-specific topographical pattern in the PFC, which could have profound implications for corticostriatal signaling in the basal ganglia.SIGNIFICANCE STATEMENTCorticostriatal connections play an important role in regulating goal-directed and habitual behavior, and neuromodulators such as cortical dopamine play an important role in behavioral flexibility. Dopamine receptor expressing D1R+ and D2R+ projection neurons in the cortex mediate the effects of cortical dopamine, but whether these neurons are anatomically organized in a manner that would explain how these neurons mediate these complex effects, is not clear. Our results show a distinct topographical organization of D1R+ and D2R+ PFC pyramidal neurons that project to distinct striatal and midbrain subregions. These results suggest that effects of cortical dopamine are mediated by anatomically localized distinct receptor- and target-defined subcircuits.

scholarly journals Retrograde Labeling Illuminates Distinct Topographical Organization of D1 and D2 Receptor-Positive Pyramidal Neurons in the Prefrontal Cortex of Mice

eNeuro ◽  
2020 ◽  
Vol 7 (5) ◽  
pp. ENEURO.0194-20.2020
Author(s):  
Sara M. Green ◽  
Sanya Nathani ◽  
Joseph Zimmerman ◽  
David Fireman ◽  
Nikhil M. Urs
Keyword(s):  
Prefrontal Cortex ◽  
Pyramidal Neurons ◽  
D2 Receptor ◽  
Retrograde Labeling ◽  
Topographical Organization

scholarly journals Age-dependent actions of dopamine on inhibitory synaptic transmission in superficial layers of mouse prefrontal cortex

2013 ◽  
Vol 109 (5) ◽  
pp. 1323-1332 ◽  
Author(s):  
Kush Paul ◽  
Charles L. Cox
Keyword(s):  
Prefrontal Cortex ◽  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
D2 Receptor ◽  
Early Time ◽  
Inhibitory Response ◽  
Cellular Level ◽  
Inhibitory Synaptic Transmission ◽  
Time Period

Numerous developmental changes in the nervous system occur during the first several weeks of the rodent lifespan. Therefore, many characteristics of neuronal function described at the cellular level from in vitro slice experiments conducted during this early time period may not generalize to adult ages. We investigated the effect of dopamine (DA) on inhibitory synaptic transmission in superficial layers of the medial prefrontal cortex (PFC) in prepubertal [postnatal age (P; days) 12–20], periadolescent (P30–48), and adult (P70–100) mice. The PFC is associated with higher-level cognitive functions, such as working memory, and is associated with initiation, planning, and execution of actions, as well as motivation and cognition. It is innervated by DA-releasing fibers that arise from the ventral tegmental area. In slices from prepubertal mice, DA produced a biphasic modulation of inhibitory postsynaptic currents (IPSCs) recorded in layer II/ III pyramidal neurons. Activation of D2-like receptors leads to an early suppression of the evoked IPSC, which was followed by a longer-lasting facilitation of the IPSC mediated by D1-like DA receptors. In periadolescent mice, the D2 receptor-mediated early suppression was significantly smaller compared with the prepubertal animals and absent in adult animals. Furthermore, we found significant differences in the DA-mediated lasting enhancement of the inhibitory response among the developmental groups. Our findings suggest that behavioral paradigms that elicit dopaminergic release in the PFC differentially modulate inhibition of excitatory pyramidal neuron output in prepuberty compared with periadolescence and adulthood in the superficial layers (II/III) of the cortex.

scholarly journals Effects of Chemogenetic Inhibition of D1 or D2 Receptor-Containing Neurons of the Substantia Nigra and Striatum in Mice With Tourette Syndrome

2021 ◽  
Vol 14 ◽  
Author(s):  
Lixue Lin ◽  
Yuye Lan ◽  
He Zhu ◽  
Lingling Yu ◽  
Shuang Wu ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Tourette Syndrome ◽  
D2 Receptor ◽  
Dorsal Striatum ◽  
Stereotyped Behavior ◽  
D1 Receptor ◽  
Substantia Nigra Pars Compacta ◽  
Motor Functions ◽  
New Treatment ◽  
Immunofluorescence Labeling

As tourette syndrome (TS) is a common neurobehavioral disorder, the primary symptoms of which include behavioral stereotypies. Dysfunction of the substantia nigra–striatum network could be the main pathogenesis of TS, which is closely associated with dopamine (DA) and its receptors. TS is often resistant to conventional treatments. Therefore, it is necessary to investigate the neurobiological mechanisms underlying its pathogenesis. In this study, we investigated whether chemogenetic activation or inhibition of dopaminergic D1 receptor (D1R)- or D2 receptor (D2R)-containing neurons in the substantia nigra pars compacta (SNpc) or dorsal striatum (dSTR) affected the stereotyped behavior and motor functions of TS mice. Intraperitoneal injection of 3,3′-iminodipropionitrile (IDPN) was used to induce TS in mice. Stereotyped behavior test and open-field, rotarod, and grip strength tests were performed to evaluate stereotyped behavior and motor functions, respectively. Immunofluorescence labeling was used to detect the co-labeling of virus fluorescence and D1R or D2R. We found that chemogenetic inhibition of D1R- or D2R-containing neurons in the SNpc and dSTR alleviated behavioral stereotypies and motor functions in TS mice. Chemogenetic activation of D1R-containing neurons in the dSTR aggravated behavioral stereotypies and motor functions in vehicle-treated mice, but neither was aggravated in TS mice. In conclusion, chemogenetic inhibition of D1R- or D2R-containing neurons in the SNpc and dSTR alleviated behavioral stereotypies of TS, providing a new treatment target for TS. Moreover, the activation of D1R-containing neurons in the dSTR may contribute to the pathogenesis of TS, which can be chosen as a more precise target for treatment.

scholarly journals Cell-type specific D1 dopamine receptor modulation of projection neurons and interneurons in the prefrontal cortex

2018 ◽  
Author(s):  
Paul G. Anastasiades ◽  
Christina Boada ◽  
Adam G. Carter
Keyword(s):  
Prefrontal Cortex ◽  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
D1 Receptor ◽  
Receptor Expression ◽  
D1 Receptors ◽  
Projection Neurons ◽  
Specific Cell ◽  
Action Potential Firing ◽  
Receptor Modulation

ABSTRACTDopamine modulation in the prefrontal cortex (PFC) mediates diverse effects on neuronal physiology and function, but the expression of dopamine receptors at sub-populations of pyramidal neurons and interneurons remains unresolved. Here, we examine D1 receptor expression and modulation at specific cell types and layers in the mouse prelimbic PFC. We first show that D1 receptors are enriched in pyramidal neurons in both layers 5 and 6, and that these cells project intra-telencephalically, rather than to sub-cortical structures. We then find that D1 receptors are also present in interneurons, and enriched in VIP+ interneurons that co-expresses calretinin, but absent from PV+ and SOM+ interneurons. Finally, we determine that D1 receptors strongly and selectively enhance action potential firing in only a subset of these cortico-cortical neurons and VIP+ interneurons. Our findings define several novel sub-populations of D1+ neurons, highlighting how modulation via D1 receptors can influence both excitatory and disinhibitory micro-circuits in the PFC.

scholarly journals Discrete and Continuous Cell Identities of the Adult Murine Striatum

2019 ◽  
Author(s):  
Geoffrey Stanley ◽  
Ozgun Gokce ◽  
Robert C. Malenka ◽  
Thomas C. Südhof ◽  
Stephen R. Quake
Keyword(s):  
Dopamine Receptor ◽  
D2 Receptor ◽  
Spatial Relationship ◽  
Cell Types ◽  
Projection Neurons ◽  
Anatomical Location ◽  
D2 Dopamine Receptors ◽  
Spatial Gradients ◽  
Dopamine Receptor 1 ◽  
Combinatorial Mechanism

AbstractThe striatum is a large brain region containing two major cell types: D1 (dopamine receptor 1) and D2 (dopamine receptor 2) expressing spiny projection neurons (SPNs). We generated a cell type atlas of the adult murine striatum using single-cell RNA-seq of SPNs combined with quantitative RNAin situhybridization (ISH). We developed a novel computational pipeline that distinguishes discrete versus continuous cell identities in scRNA-seq data, and used it to show that SPNs in the striatum can be classified into four discrete types that reside in discrete anatomical clusters or are spatially intermingled. Within each discrete type, we find multiple independent axes of continuous cell identity that map to spatial gradients and whose genes are conserved between discrete types. These gradients correlate well to previously-mapped gradients of connectivity. Using these insights, we discovered multiple novel spatially localized region of the striatum, one of which contains patch-D2 SPNs that expressTac1, Htr7, andTh. Intriguingly, we found one subtype that strongly co-expresses both D1 and D2 dopamine receptors, and uniquely expresses a rare D2 receptor splice variant. These results collectively suggest an organizational principal of neuron identity in which major neuron types can be separated into discrete classes with little overlap and no implied spatial relationship. However these discrete classes are then continuously subdivided by multiple spatial gradients of expression defining anatomical location via a combinatorial mechanism. Finally, they suggest that neuronal circuitry has a substructure at far higher resolution than is typically interrogated which is defined by the precise identity and location of a neuron.

scholarly journals Pharmacological blockade of dopamine D1- or D2-receptor in the prefrontal cortex induces attentional impairment in the object-based attention test through different neuronal circuits in mice

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Bolati Wulaer ◽  
Kazuo Kunisawa ◽  
Moeka Tanabe ◽  
Aika Yanagawa ◽  
Kuniaki Saito ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Neuronal Activity ◽  
D2 Receptor ◽  
Brain Regions ◽  
D2 Receptors ◽  
Neuronal System ◽  
Neuronal Circuits ◽  
D1 And D2 Receptors ◽  
Object Based ◽  
Pharmacological Blockade

AbstractDopamine is a key neurotransmitter that regulates attention through dopamine D1 and D2-receptors in the prefrontal cortex (PFC). We previously developed an object-based attention test (OBAT) to evaluate attention in mice. Disruption of the dopaminergic neuronal system in the PFC induced attentional impairment in the OBAT. However, previous studies have not systematically examined which specific brain regions are associated with the blockade of PFC dopamine D1 and D2-receptors in the OBAT. In this study, we investigated the association of dopamine D1 and D2-receptors in the PFC with attention and neuronal activity in diverse brain regions. We found that both dopamine D1 and D2-receptor antagonists induced attentional impairment in the OBAT by bilateral microinjection into the PFC of mice, suggesting that both dopamine D1 and D2-receptors were associated with attention in the OBAT. Our analysis of the neuronal activity as indicated by c-Fos expression in 11 different brain regions showed that based on the antagonist types, there was selective activation of several brain regions. Overall, this study suggests that both dopamine D1 and D2-receptors play a role in attention through different neuronal circuits in the PFC of mice.

scholarly journals The Role of Mesostriatal Dopamine System and Corticostriatal Glutamatergic Transmission in Chronic Pain

2021 ◽  
Vol 11 (10) ◽  
pp. 1311
Author(s):  
Barbara Ziółkowska
Keyword(s):  
Chronic Pain ◽  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
D2 Receptor ◽  
Dorsal Striatum ◽  
Persistent Pain ◽  
Pain Modulation ◽  
Medium Spiny Neurons ◽  
Analgesic Effects

There is increasing recognition of the involvement of the nigrostriatal and mesolimbic dopamine systems in the modulation of chronic pain. The first part of the present article reviews the evidence indicating that dopamine exerts analgesic effects during persistent pain by stimulating the D2 receptors in the dorsal striatum and nucleus accumbens (NAc). Thereby, dopamine inhibits striatal output via the D2 receptor-expressing medium spiny neurons (D2-MSN). Dopaminergic neurotransmission in the mesostriatal pathways is hampered in chronic pain states and this alteration maintains and exacerbates pain. The second part of this article focuses on the glutamatergic inputs from the medial prefrontal cortex to the NAc, their activity changes in chronic pain, and their role in pain modulation. Finally, interactions between dopaminergic and glutamatergic inputs to the D2-MSN are considered in the context of persistent pain. Studies using novel techniques indicate that pain is regulated oppositely by two independent dopaminergic circuits linking separate parts of the ventral tegmental area and of the NAc, which also interact with distinct regions of the medial prefrontal cortex.

scholarly journals A Novel Dopamine Receptor Signaling Unit in Brain: Heterooligomers of D1 And D2 Dopamine Receptors

2007 ◽  
Vol 7 ◽  
pp. 58-63 ◽  
Author(s):  
Susan R. George ◽  
Brian F. O'Dowd
Keyword(s):  
Dopamine Receptor ◽  
Calcium Release ◽  
D2 Receptor ◽  
Binding Pocket ◽  
Calcium Signal ◽  
Molecular Entity ◽  
D2 Dopamine Receptors ◽  
Receptor Field ◽  
D1 And D2 Receptors ◽  
Definition Of

The ability of G protein coupled receptors to heterooligomerize and create novel signaling complexes has demonstrated the tremendous potential of these receptors to access diverse signaling cascades, as well as to modulate the nature of the transduced signal. In the dopamine receptor field, the existence of a D1-like receptor in brain that activated phospatidylinositol turnover has been shown, but definition of the molecular entity remained elusive. We discovered that the D1 and D2 receptors form a heterooligomer, which on activation of both receptors, coupled to Gq to activate phospholipase C and generate intracellular calcium release. The activation of Gq by the D1-D2 heterooligomer has been shown to occur in cells expressing both receptors, as well as in striatum, distinct from Gs/olf or Gi/o activation by the D1 and D2 receptor homooligomers, respectively. The activation of the D1-D2 receptor heterooligomer in brain led to a calcium signal–mediated increase in phosphorylation of calmodulin kinase lla. The calcium signal rapidly desensitized and the receptors cointernalized after occupancy of either the D1 or D2 binding pocket. Thus, the D1-D2 heterooligomer directly links the action of dopamine to rapid calcium signaling and likely has important effects on dopamine-mediated synaptic plasticity and its functional correlates in brain.

Sign in / Sign up

Export Citation Format

Share Document