scholarly journals Repression of Dlx1/2 Signaling by Nolz-1/Znf503 is Essential for Parcellation of the Striatal Complex into Dorsal and Ventral Striatum

2018 ◽  
Author(s):  
Kuan-Ming Lu ◽  
Shih-Yun Chen ◽  
Hsin-An Ko ◽  
Ting-Hao Huang ◽  
Janice Hsin-Jou Hao ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Ventral Striatum ◽  
Dorsal Striatum ◽  
Clinical Importance ◽  
Projection Neurons ◽  
Striatal Neurons ◽  
Addictive Disorders ◽  
Striatal Projection Neurons ◽  
Cells Of Origin ◽  
Set Up

ABSTRACTThe division of the striatum into dorsal and ventral districts is of central clinical importance. The dorsal striatum is differentially affected in Huntington’s disease, dopamine in the ventral striatum is differentially spared in Parkinson’s disease, and human brain imaging studies implicate the ventral striatum in addictive disorders. If fits that the dorsal striatum contains the cells of origin of the direct and indirect basal ganglia pathways for motor control. The ventral striatum is a node in neural circuits related to motivation and affect. Despite these striking neurobiologic contrasts, there is almost no information about how the dorsal and ventral divisions of the striatum are set up during development. Here, we demonstrate that interactions between the two key transcription factors Nolz-1 and Dlx1/2 control the migratory paths of developing striatal neurons to the dorsal or ventral striatum. Moreover, these same transcription factors control the cell identity of striatal projection neurons in both the dorsal and ventral striatum including the cell origin of the direct and indirect pathways. We show that Nolz-1 suppresses Dlx1/2 expression. Deletion of Nolz-1 or over-expression of Dlx1/2 can produce a striatal phenotype characterized by withered dorsal striatum and a swollen ventral striatum, and that we can rescue this phenotype by manipulating the interactions between Nolz-1 and Dlx1/2 transcription factors. This evidence suggests that the fundamental basis for divisions of the striatum known to be differentially vulnerable at maturity is already encoded by the time embryonic striatal neurons begin their migrations into the developing striatum.

scholarly journals Parcellation of the striatal complex into dorsal and ventral districts

2020 ◽  
Vol 117 (13) ◽  
pp. 7418-7429 ◽  
Author(s):  
Shih-Yun Chen ◽  
Kuan-Ming Lu ◽  
Hsin-An Ko ◽  
Ting-Hao Huang ◽  
Janice Hsin-Jou Hao ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Ventral Striatum ◽  
Dorsal Striatum ◽  
Clinical Importance ◽  
Projection Neurons ◽  
Striatal Neurons ◽  
Striatal Projection Neurons ◽  
Tier System ◽  
And Migration ◽  
Set Up

The striatal complex of basal ganglia comprises two functionally distinct districts. The dorsal district controls motor and cognitive functions. The ventral district regulates the limbic function of motivation, reward, and emotion. The dorsoventral parcellation of the striatum also is of clinical importance as differential striatal pathophysiologies occur in Huntington’s disease, Parkinson’s disease, and drug addiction disorders. Despite these striking neurobiologic contrasts, it is largely unknown how the dorsal and ventral divisions of the striatum are set up. Here, we demonstrate that interactions between the two key transcription factors Nolz-1 and Dlx1/2 control the migratory paths of striatal neurons to the dorsal or ventral striatum. Moreover, these same transcription factors control the cell identity of striatal projection neurons in both the dorsal and the ventral striata including the D1-direct and D2-indirect pathways. We show that Nolz-1, through the I12b enhancer, represses Dlx1/2, allowing normal migration of striatal neurons to dorsal and ventral locations. We demonstrate that deletion, up-regulation, and down-regulation of Nolz-1 and Dlx1/2 can produce a striatal phenotype characterized by a withered dorsal striatum and an enlarged ventral striatum and that we can rescue this phenotype by manipulating the interactions between Nolz-1 and Dlx1/2 transcription factors. Our study indicates that the two-tier system of striatal complex is built by coupling of cell-type identity and migration and suggests that the fundamental basis for divisions of the striatum known to be differentially vulnerable at maturity is already encoded by the time embryonic striatal neurons begin their migrations into developing striata.

scholarly journals KV7 Channels Regulate Firing during Synaptic Integration in GABAergic Striatal Neurons

2015 ◽  
Vol 2015 ◽  
pp. 1-18 ◽  
Author(s):  
M. Belén Pérez-Ramírez ◽  
Antonio Laville ◽  
Dagoberto Tapia ◽  
Mariana Duhne ◽  
Esther Lara-González ◽  
...  
Keyword(s):  
Muscarinic Receptors ◽  
Synaptic Integration ◽  
Projection Neurons ◽  
Striatal Neurons ◽  
Kv7 Channels ◽  
Striatal Projection Neurons ◽  
Voltage Dependent ◽  
Cognitive Information ◽  
Firing Properties ◽  
The Impact

Striatal projection neurons (SPNs) process motor and cognitive information. Their activity is affected by Parkinson’s disease, in which dopamine concentration is decreased and acetylcholine concentration is increased. Acetylcholine activates muscarinic receptors in SPNs. Its main source is the cholinergic interneuron that responds with a briefer latency than SPNs during a cortical command. Therefore, an important question is whether muscarinic G-protein coupled receptors and their signaling cascades are fast enough to intervene during synaptic responses to regulate synaptic integration and firing. One of the most known voltage dependent channels regulated by muscarinic receptors is theKV7/KCNQ channel. It is not known whether these channels regulate the integration of suprathreshold corticostriatal responses. Here, we study the impact of cholinergic muscarinic modulation on the synaptic response of SPNs by regulatingKV7 channels. We found thatKV7 channels regulate corticostriatal synaptic integration and that this modulation occurs in the dendritic/spines compartment. In contrast, it is negligible in the somatic compartment. This modulation occurs on sub- and suprathreshold responses and lasts during the whole duration of the responses, hundreds of milliseconds, greatly altering SPNs firing properties. This modulation affected the behavior of the striatal microcircuit.

scholarly journals GABA uptake transporters support dopamine release in dorsal striatum with maladaptive downregulation in a parkinsonism model

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Bradley M. Roberts ◽  
Natalie M. Doig ◽  
Katherine R. Brimblecombe ◽  
Emanuel F. Lopes ◽  
Ruth E. Siddorn ◽  
...  
Keyword(s):  
Dorsal Striatum ◽  
Gaba Uptake ◽  
Projection Neurons ◽  
Nucleus Accumbens Core ◽  
Dorsolateral Striatum ◽  
Striatal Projection Neurons ◽  
Maladaptive Plasticity ◽  
Uptake Transporters ◽  
Da Release ◽  
Accumbens Core

Abstract Striatal dopamine (DA) is critical for action and learning. Recent data show that DA release is under tonic inhibition by striatal GABA. Ambient striatal GABA tone on striatal projection neurons can be determined by plasma membrane GABA uptake transporters (GATs) located on astrocytes and neurons. However, whether striatal GATs and astrocytes determine DA output are unknown. We reveal that DA release in mouse dorsolateral striatum, but not nucleus accumbens core, is governed by GAT-1 and GAT-3. These GATs are partly localized to astrocytes, and are enriched in dorsolateral striatum compared to accumbens core. In a mouse model of early parkinsonism, GATs are downregulated, tonic GABAergic inhibition of DA release augmented, and nigrostriatal GABA co-release attenuated. These data define previously unappreciated and important roles for GATs and astrocytes in supporting DA release in striatum, and reveal a maladaptive plasticity in early parkinsonism that impairs DA output in vulnerable striatal regions.

Coding of the long-term value of multiple future rewards in the primate striatum

2013 ◽  
Vol 109 (4) ◽  
pp. 1140-1151 ◽  
Author(s):  
Hiroshi Yamada ◽  
Hitoshi Inokawa ◽  
Naoyuki Matsumoto ◽  
Yasumasa Ueda ◽  
Kazuki Enomoto ◽  
...  
Keyword(s):  
Reinforcement Learning ◽  
Learning Theories ◽  
Projection Neurons ◽  
Striatal Neurons ◽  
Striatal Projection Neurons ◽  
Positive Correlations ◽  
Task Trial ◽  
The Cost ◽  
Near Future

Decisions maximizing benefits involve a tradeoff between the quantity of a reward and the cost of elapsed time until an animal receives it. The estimation of long-term reward values is critical to attain the most desirable outcomes over a certain period of time. Reinforcement learning theories have established algorithms to estimate the long-term reward values of multiple future rewards in which the values of future rewards are discounted as a function of how many steps of choices are necessary to achieve them. Here, we report that presumed striatal projection neurons represent the long-term values of multiple future rewards estimated by a standard reinforcement learning model while monkeys are engaged in a series of trial-and-error choices and adaptive decisions for multiple rewards. We found that the magnitude of activity of a subset of neurons was positively correlated with the long-term reward values, and that of another subset of neurons was negatively correlated throughout the entire decision-making process in individual trials: from the start of the task trial, estimation of the values and their comparison among alternatives, choice execution, and evaluation of the received rewards. An idiosyncratic finding was that neurons showing negative correlations represented reward values in the near future (high discounting), while neurons showing positive correlations represented reward values not only in the near future, but also in the far future (low discounting). These findings provide a new insight that long-term value signals are embedded in two subsets of striatal neurons as high and low discounting of multiple future rewards.

scholarly journals Dopamine D4 Receptor Is a Regulator of Morphine-Induced Plasticity in the Rat Dorsal Striatum

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 31
Author(s):  
Alicia Rivera ◽  
Diana Suárez-Boomgaard ◽  
Cristina Miguelez ◽  
Alejandra Valderrama-Carvajal ◽  
Jérôme Baufreton ◽  
...  
Keyword(s):  
Critical Role ◽  
Combined Treatment ◽  
Dorsal Striatum ◽  
Prolonged Treatment ◽  
Projection Neurons ◽  
Spine Density ◽  
Dopamine D4 Receptor ◽  
Striatal Projection Neurons ◽  
D4 Receptor

Long-term exposition to morphine elicits structural and synaptic plasticity in reward-related regions of the brain, playing a critical role in addiction. However, morphine-induced neuroadaptations in the dorsal striatum have been poorly studied despite its key function in drug-related habit learning. Here, we show that prolonged treatment with morphine triggered the retraction of the dendritic arbor and the loss of dendritic spines in the dorsal striatal projection neurons (MSNs). In an attempt to extend previous findings, we also explored whether the dopamine D4 receptor (D4R) could modulate striatal morphine-induced plasticity. The combined treatment of morphine with the D4R agonist PD168,077 produced an expansion of the MSNs dendritic arbors and restored dendritic spine density. At the electrophysiological level, PD168,077 in combination with morphine altered the electrical properties of the MSNs and decreased their excitability. Finally, results from the sustantia nigra showed that PD168,077 counteracted morphine-induced upregulation of μ opioid receptors (MOR) in striatonigral projections and downregulation of G protein-gated inward rectifier K+ channels (GIRK1 and GIRK2) in dopaminergic cells. The present results highlight the key function of D4R modulating morphine-induced plasticity in the dorsal striatum. Thus, D4R could represent a valuable pharmacological target for the safety use of morphine in pain management.

scholarly journals Unbiased identification of novel transcription factors in striatal compartmentation and striosome maturation

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Maria-Daniela Cirnaru ◽  
Sicheng Song ◽  
Kizito-Tshitoko Tshilenge ◽  
Chuhyon Corwin ◽  
Justyna Mleczko ◽  
...  
Keyword(s):  
Disease Modeling ◽  
Gene Families ◽  
Projection Neurons ◽  
Open Chromatin ◽  
Striatal Neurons ◽  
Striatal Projection Neurons ◽  
Open Chromatin Region ◽  
Human Ipsc

Many diseases are linked to dysregulation of the striatum. Striatal function depends on neuronal compartmentation into striosomes and matrix. Striatal projection neurons are GABAergic medium spiny neurons (MSNs), subtyped by selective expression of receptors, neuropeptides, and other gene families. Neurogenesis of the striosome and matrix occurs in separate waves, but the factors regulating compartmentation and neuronal differentiation are largely unidentified. We performed RNA- and ATAC-seq on sorted striosome and matrix cells at postnatal day 3, using the Nr4a1-EGFP striosome reporter mouse. Focusing on the striosome, we validated the localization and/or role of Irx1, Foxf2, Olig2, and Stat1/2 in the developing striosome and the in vivo enhancer function of a striosome-specific open chromatin region 4.4 Kb downstream of Olig2. These data provide novel tools to dissect and manipulate the networks regulating MSN compartmentation and differentiation, including in human iPSC-derived striatal neurons for disease modeling and drug discovery.

scholarly journals D1 and D2 systems converge in the striatum to update goal-directed learning

2019 ◽  
Author(s):  
Miriam Matamales ◽  
Alice E. McGovern ◽  
Jia Dai Mi ◽  
Stuart B. Mazzone ◽  
Bernard W. Balleine ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Behavioral Control ◽  
Dorsal Striatum ◽  
Projection Neurons ◽  
Extinction Learning ◽  
Striatal Projection Neurons ◽  
New Learning ◽  
Large Ensembles ◽  
Directed Learning

AbstractExtinction learning allows animals to withhold voluntary actions that are no longer related to reward and so provides a major source of behavioral control. Although such learning is thought to depend on dopamine signals in the striatum, the way the circuits mediating goal-directed control are reorganized during new learning remains unknown. Here, by mapping a dopamine-dependent transcriptional activation marker in large ensembles of striatal projection neurons (SPNs) expressing dopamine receptor type 1 (D1-SPNs) or 2 (D2-SPNs) in mice, we demonstrate an extensive and dynamic D2- to D1-SPN trans-modulation across the dorsal striatum that is necessary for updating previous goal-directed learning. Our findings suggest that D2-SPNs suppress the influence of outdated D1-SPN plasticity within functionally relevant striatal territories to reshape volitional action.

scholarly journals Dopamine D2/3 Receptor Availabilities and Evoked Dopamine Release in Striatum Differentially Predict Impulsivity and Novelty Preference in Roman High- and Low-Avoidance Rats

2020 ◽  
Author(s):  
Lidia Bellés ◽  
Andrea Dimiziani ◽  
Stergios Tsartsalis ◽  
Philippe Millet ◽  
François R Herrmann ◽  
...  
Keyword(s):  
Ventral Striatum ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Emission ◽  
Dorsal Striatum ◽  
Reaction Time Task ◽  
Emission Computed Tomography ◽  
Novelty Preference ◽  
Da Release

Abstract Background Impulsivity and novelty preference are both associated with an increased propensity to develop addiction-like behaviors, but their relationship and respective underlying dopamine (DA) underpinnings are not fully elucidated. Methods We evaluated a large cohort (n = 49) of Roman high- and low-avoidance rats using single photon emission computed tomography to concurrently measure in vivo striatal D2/3 receptor (D2/3R) availability and amphetamine (AMPH)-induced DA release in relation to impulsivity and novelty preference using a within-subject design. To further examine the DA-dependent processes related to these traits, midbrain D2/3-autoreceptor levels were measured using ex vivo autoradiography in the same animals. Results We replicated a robust inverse relationship between impulsivity, as measured with the 5-choice serial reaction time task, and D2/3R availability in ventral striatum and extended this relationship to D2/3R levels measured in dorsal striatum. Novelty preference was positively related to impulsivity and showed inverse associations with D2/3R availability in dorsal striatum and ventral striatum. A high magnitude of AMPH-induced DA release in striatum predicted both impulsivity and novelty preference, perhaps owing to the diminished midbrain D2/3-autoreceptor availability measured in high-impulsive/novelty-preferring Roman high-avoidance animals that may amplify AMPH effect on DA transmission. Mediation analyses revealed that while D2/3R availability and AMPH-induced DA release in striatum are both significant predictors of impulsivity, the effect of striatal D2/3R availability on novelty preference is fully mediated by evoked striatal DA release. Conclusions Impulsivity and novelty preference are related but mediated by overlapping, yet dissociable, DA-dependent mechanisms in striatum that may interact to promote the emergence of an addiction-prone phenotype.

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