scholarly journals Molecular organization and timing of Wnt1 expression define cohorts of midbrain dopamine neuron progenitors in vivo

2011 ◽  
Vol 519 (15) ◽  
pp. 2978-3000 ◽  
Author(s):  
Ashly Brown ◽  
Jason T. Machan ◽  
Lindsay Hayes ◽  
Mark Zervas
Keyword(s):  
Dopamine Neuron ◽  
Molecular Organization ◽  
Midbrain Dopamine ◽  
Wnt1 Expression

scholarly journals SFRP1 and SFRP2 Dose-Dependently Regulate Midbrain Dopamine Neuron Development In Vivo and in Embryonic Stem Cells

Stem Cells ◽  
2012 ◽  
Vol 30 (5) ◽  
pp. 865-875 ◽  
Author(s):  
Julianna Kele ◽  
Emma R. Andersson ◽  
J. Carlos Villaescusa ◽  
Lukas Cajanek ◽  
Clare L. Parish ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Dopamine Neuron ◽  
Neuron Development ◽  
Midbrain Dopamine

scholarly journals Genetic dissection of midbrain dopamine neuron development in vivo

2012 ◽  
Vol 372 (2) ◽  
pp. 249-262 ◽  
Author(s):  
Debra Ellisor ◽  
Caroline Rieser ◽  
Bettina Voelcker ◽  
Jason T. Machan ◽  
Mark Zervas
Keyword(s):  
Dopamine Neuron ◽  
Genetic Dissection ◽  
Neuron Development ◽  
Midbrain Dopamine

scholarly journals In vivo patch-clamp recordings reveal distinct subthreshold signatures and threshold dynamics of midbrain dopamine neurons

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Kanako Otomo ◽  
Jessica Perkins ◽  
Anand Kulkarni ◽  
Strahinja Stojanovic ◽  
Jochen Roeper ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Dopamine Neuron ◽  
Dopamine Neurons ◽  
Firing Patterns ◽  
Action Potential Threshold ◽  
Midbrain Dopamine ◽  
Potential Threshold ◽  
Midbrain Dopamine Neurons

AbstractThe in vivo firing patterns of ventral midbrain dopamine neurons are controlled by afferent and intrinsic activity to generate sensory cue and prediction error signals that are essential for reward-based learning. Given the absence of in vivo intracellular recordings during the last three decades, the subthreshold membrane potential events that cause changes in dopamine neuron firing patterns remain unknown. To address this, we established in vivo whole-cell recordings and obtained over 100 spontaneously active, immunocytochemically-defined midbrain dopamine neurons in isoflurane-anaesthetized adult mice. We identified a repertoire of subthreshold membrane potential signatures associated with distinct in vivo firing patterns. Dopamine neuron activity in vivo deviated from single-spike pacemaking by phasic increases in firing rate via two qualitatively distinct biophysical mechanisms: 1) a prolonged hyperpolarization preceding rebound bursts, accompanied by a hyperpolarizing shift in action potential threshold; and 2) a transient depolarization leading to high-frequency plateau bursts, associated with a depolarizing shift in action potential threshold. Our findings define a mechanistic framework for the biophysical implementation of dopamine neuron firing patterns in the intact brain.

scholarly journals Subthreshold repertoire and threshold dynamics of midbrain dopamine neuron firing in vivo

2020 ◽  
Author(s):  
Kanako Otomo ◽  
Jessica Perkins ◽  
Anand Kulkarni ◽  
Strahinja Stojanovic ◽  
Jochen Roeper ◽  
...  
Keyword(s):  
Action Potential ◽  
Prediction Error ◽  
Dopamine Neuron ◽  
Dopamine Neurons ◽  
Threshold Dynamics ◽  
Action Potential Threshold ◽  
Midbrain Dopamine ◽  
Potential Threshold ◽  
Midbrain Dopamine Neurons

AbstractThe firing pattern of ventral midbrain dopamine neurons is controlled by afferent and intrinsic activity to generate prediction error signals that are essential for reward-based learning. Given the absence of intracellular in vivo recordings in the last three decades, the subthreshold membrane potential events that cause changes in dopamine neuron firing patterns remain unknown. By establishing stable in vivo whole-cell recordings of >100 spontaneously active midbrain dopamine neurons in anaesthetized mice, we identified the repertoire of subthreshold membrane potential signatures associated with distinct in vivo firing patterns. We demonstrate that dopamine neuron in vivo activity deviates from a single spike pacemaker pattern by eliciting transient increases in firing rate generated by at least two diametrically opposing biophysical mechanisms: a transient depolarization resulting in high frequency plateau bursts associated with a reactive, depolarizing shift in action potential threshold; and a prolonged hyperpolarization preceding slower rebound bursts characterized by a predictive, hyperpolarizing shift in action potential threshold. Our findings therefore illustrate a framework for the biophysical implementation of prediction error and sensory cue coding in dopamine neurons by tuning action potential threshold dynamics.

scholarly journals Neuroprotective Potential of a Small Molecule RET Agonist in Cultured Dopamine Neurons and Hemiparkinsonian Rats

2021 ◽  
pp. 1-24
Author(s):  
Juho-Matti Renko ◽  
Arun Kumar Mahato ◽  
Tanel Visnapuu ◽  
Konsta Valkonen ◽  
Mati Karelson ◽  
...  
Keyword(s):  
Mapk Signaling ◽  
Dopamine Neurons ◽  
Dopamine Depletion ◽  
Wild Type ◽  
Disease Modifying Therapy ◽  
Immortalized Cells ◽  
Midbrain Dopamine ◽  
6 Hydroxydopamine

Background: Parkinson’s disease (PD) is a progressive neurological disorder where loss of dopamine neurons in the substantia nigra and dopamine depletion in the striatum cause characteristic motor symptoms. Currently, no treatment is able to halt the progression of PD. Glial cell line-derived neurotrophic factor (GDNF) rescues degenerating dopamine neurons both in vitro and in animal models of PD. When tested in PD patients, however, the outcomes from intracranial GDNF infusion paradigms have been inconclusive, mainly due to poor pharmacokinetic properties. Objective: We have developed drug-like small molecules, named BT compounds that activate signaling through GDNF’s receptor, the transmembrane receptor tyrosine kinase RET, both in vitro and in vivo and are able to penetrate through the blood-brain barrier. Here we evaluated the properties of BT44, a second generation RET agonist, in immortalized cells, dopamine neurons and rat 6-hydroxydopamine model of PD. Methods: We used biochemical, immunohistochemical and behavioral methods to evaluate the effects of BT44 on dopamine system in vitro and in vivo. Results: BT44 selectively activated RET and intracellular pro-survival AKT and MAPK signaling pathways in immortalized cells. In primary midbrain dopamine neurons cultured in serum-deprived conditions, BT44 promoted the survival of the neurons derived from wild-type, but not from RET knockout mice. BT44 also protected cultured wild-type dopamine neurons from MPP +-induced toxicity. In a rat 6-hydroxydopamine model of PD, BT44 reduced motor imbalance and could have protected dopaminergic fibers in the striatum. Conclusion: BT44 holds potential for further development into a novel, possibly disease-modifying therapy for PD.

scholarly journals Mapping and Functional Characterization of the TAF11 Interaction with TFIIA

2005 ◽  
Vol 25 (3) ◽  
pp. 945-957 ◽  
Author(s):  
M. M. Robinson ◽  
G. Yatherajam ◽  
R. T. Ranallo ◽  
A. Bric ◽  
M. R. Paule ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Regulation Of Gene Expression ◽  
Small Subunit ◽  
Molecular Organization ◽  
Functional Link ◽  
Essential Information ◽  
Histone Fold ◽  
Histone Fold Domain ◽  
Promoter Dna

ABSTRACT TFIIA interacts with TFIID via association with TATA binding protein (TBP) and TBP-associated factor 11 (TAF11). We previously identified a mutation in the small subunit of TFIIA (toa2-I27K) that is defective for interaction with TAF11. To further explore the functional link between TFIIA and TAF11, the toa2-I27K allele was utilized in a genetic screen to isolate compensatory mutants in TAF11. Analysis of these compensatory mutants revealed that the interaction between TAF11 and TFIIA involves two distinct regions of TAF11: the highly conserved histone fold domain and the N-terminal region. Cells expressing a TAF11 allele defective for interaction with TFIIA exhibit conditional growth phenotypes and defects in transcription. Moreover, TAF11 imparts changes to both TFIIA-DNA and TBP-DNA contacts in the context of promoter DNA. These alterations appear to enhance the formation and stabilization of the TFIIA-TBP-DNA complex. Taken together, these studies provide essential information regarding the molecular organization of the TAF11-TFIIA interaction and define a mechanistic role for this association in the regulation of gene expression in vivo.

scholarly journals c-Jun mediates axotomy-induced dopamine neuron death in vivo

2001 ◽  
Vol 98 (23) ◽  
pp. 13385-13390 ◽  
Author(s):  
S. J. Crocker ◽  
W. R. Lamba ◽  
P. D. Smith ◽  
S. M. Callaghan ◽  
R. S. Slack ◽  
...  
Keyword(s):  
Dopamine Neuron ◽  
Neuron Death

scholarly journals The TFIID Components Human TAFII140 andDrosophila BIP2 (TAFII155) Are Novel Metazoan Homologues of Yeast TAFII47 Containing a Histone Fold and a PHD Finger

2001 ◽  
Vol 21 (15) ◽  
pp. 5109-5121 ◽  
Author(s):  
Yann-Gaël Gangloff ◽  
Jean-Christophe Pointud ◽  
Sylvie Thuault ◽  
Lucie Carré ◽  
Christophe Romier ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Sequence Similarity ◽  
Protein A ◽  
Amino Acid Sequences ◽  
Molecular Organization ◽  
Phd Finger ◽  
Histone Fold ◽  
Histone Fold Domain ◽  
High Degree

ABSTRACT The RNA polymerase II transcription factor TFIID comprises the TATA binding protein (TBP) and a set of TBP-associated factors (TAFIIs). TFIID has been extensively characterized for yeast, Drosophila, and humans, demonstrating a high degree of conservation of both the amino acid sequences of the constituent TAFIIs and overall molecular organization. In recent years, it has been assumed that all the metazoan TAFIIs have been identified, yet no metazoan homologues of yeast TAFII47 (yTAFII47) and yTAFII65 are known. Both of these yTAFIIs contain a histone fold domain (HFD) which selectively heterodimerizes with that of yTAFII25. We have cloned a novel mouse protein, TAFII140, containing an HFD and a plant homeodomain (PHD) finger, which we demonstrated by immunoprecipitation to be a mammalian TFIID component. TAFII140 shows extensive sequence similarity toDrosophila BIP2 (dBIP2) (dTAFII155), which we also show to be a component of DrosophilaTFIID. These proteins are metazoan homologues of yTAFII47 as their HFDs selectively heterodimerize with dTAFII24 and human TAFII30, metazoan homologues of yTAFII25. We further show that yTAFII65 shares two domains with theDrosophila Prodos protein, a recently described potential dTAFII. These conserved domains are critical for yTAFII65 function in vivo. Our results therefore identify metazoan homologues of yTAFII47 and yTAFII65.

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