scholarly journals Impaired recruitment of dopamine neurons during working memory in mice with striatal D2 receptor overexpression

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Sevil Duvarci ◽  
Eleanor H. Simpson ◽  
Gaby Schneider ◽  
Eric R. Kandel ◽  
Jochen Roeper ◽  
...  
Keyword(s):  
Working Memory ◽  
D2 Receptor ◽  
Dopamine Neurons

scholarly journals α-Synuclein-induced dysregulation of neuronal activity contributes to murine dopamine neuron vulnerability

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Abeer Dagra ◽  
Douglas R. Miller ◽  
Min Lin ◽  
Adithya Gopinath ◽  
Fatemeh Shaerzadeh ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuronal Activity ◽  
Dopaminergic Neurons ◽  
Prolonged Exposure ◽  
D2 Receptor ◽  
Neuronal Firing ◽  
Dopamine Neurons ◽  
Loss Of Function ◽  
Therapeutic Implications

AbstractPathophysiological damages and loss of function of dopamine neurons precede their demise and contribute to the early phases of Parkinson’s disease. The presence of aberrant intracellular pathological inclusions of the protein α-synuclein within ventral midbrain dopaminergic neurons is one of the cardinal features of Parkinson’s disease. We employed molecular biology, electrophysiology, and live-cell imaging to investigate how excessive α-synuclein expression alters multiple characteristics of dopaminergic neuronal dynamics and dopamine transmission in cultured dopamine neurons conditionally expressing GCaMP6f. We found that overexpression of α-synuclein in mouse (male and female) dopaminergic neurons altered neuronal firing properties, calcium dynamics, dopamine release, protein expression, and morphology. Moreover, prolonged exposure to the D2 receptor agonist, quinpirole, rescues many of the alterations induced by α-synuclein overexpression. These studies demonstrate that α-synuclein dysregulation of neuronal activity contributes to the vulnerability of dopaminergic neurons and that modulation of D2 receptor activity can ameliorate the pathophysiology. These findings provide mechanistic insights into the insidious changes in dopaminergic neuronal activity and neuronal loss that characterize Parkinson’s disease progression with significant therapeutic implications.

Combined D1/D2 receptor stimulation under conditions of dopamine depletion impairs spatial working memory performance in humans

2005 ◽  
Vol 181 (4) ◽  
pp. 771-780 ◽  
Author(s):  
Kathryn A. Ellis ◽  
Mitul A. Mehta ◽  
Keith A. Wesnes ◽  
Stuart Armstrong ◽  
Pradeep J. Nathan
Keyword(s):  
Working Memory ◽  
Spatial Working Memory ◽  
Memory Performance ◽  
D2 Receptor ◽  
Dopamine Depletion ◽  
Receptor Stimulation

scholarly journals In Parkinson's patient-derived dopamine neurons, the triplication of α-synuclein locus induces distinctive firing pattern by impeding D2 receptor autoinhibition

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Min Lin ◽  
Phillip M. Mackie ◽  
Fatima Shaerzadeh ◽  
Joyonna Gamble-George ◽  
Douglas R. Miller ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
D2 Receptor ◽  
Neuronal Morphology ◽  
Dopamine Neurons ◽  
Firing Activity ◽  
Degree Relative ◽  
Primary Mouse ◽  
Similar Phenotype ◽  
Induced Pluripotent ◽  
D2 Receptor Agonist

AbstractPathophysiological changes in dopamine neurons precede their demise and contribute to the early phases of Parkinson’s disease (PD). Intracellular pathological inclusions of the protein α-synuclein within dopaminergic neurons are a cardinal feature of PD, but the mechanisms by which α-synuclein contributes to dopaminergic neuron vulnerability remain unknown. The inaccessibility to diseased tissue has been a limitation in studying progression of pathophysiology prior to degeneration of dopamine neurons. To address these issues, we differentiated induced pluripotent stem cells (iPSCs) from a PD patient carrying the α-synuclein triplication mutation (AST) and an unaffected first-degree relative (NAS) into dopaminergic neurons. In human-like dopamine neurons α-synuclein overexpression reduced the functional availability of D2 receptors, resulting in a stark dysregulation in firing activity, dopamine release, and neuronal morphology. We back-translated these findings into primary mouse neurons overexpressing α-synuclein and found a similar phenotype, supporting the causal role for α-synuclein. Importantly, application of D2 receptor agonist, quinpirole, restored the altered firing activity of AST-derived dopaminergic neurons to normal levels. These results provide novel insights into the pre-degenerative pathophysiological neuro-phenotype induced by α-synuclein overexpression and introduce a potential mechanism for the long-established clinical efficacy of D2 receptor agonists in the treatment of PD.

scholarly journals Assessment of Lactotroph Axis Functionality in Mice: Longitudinal Monitoring of PRL Secretion by Ultrasensitive-ELISA

Endocrinology ◽  
2015 ◽  
Vol 156 (5) ◽  
pp. 1924-1930 ◽  
Author(s):  
Anne Guillou ◽  
Nicola Romanò ◽  
Frederik Steyn ◽  
Karine Abitbol ◽  
Paul Le Tissier ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Dopamine D2 Receptor ◽  
Physiological State ◽  
D2 Receptor ◽  
Dopamine Neurons ◽  
Detection Sensitivity ◽  
Lactating Females ◽  
Freely Moving ◽  
Inhibitory Tone ◽  
Dopamine D2 Receptor Antagonist

The pattern of prolactin (PRL) secretion depends on the physiological state. Due to insufficient detection sensitivity of existing assays, the precise description of these patterns in mice is lacking. We described an ultrasensitive ELISA assay that can detect mouse PRL in small fractions of whole blood, allowing longitudinal studies of PRL secretion profiles in freely moving mice. Over a 24-hour period, males displayed no oscillation in PRL levels, whereas virgin and lactating females showed large pulses. Peaks of PRL secretion reached 30–40 ng/mL in lactating female mice and rarely exceeded 10 ng/mL in virgin females. These pulses of PRL in lactating females were associated with suckling. The return of pups after an experimental 12-hour weaning induced a pulse of PRL release, reaching 100 ng/mL. This approach also enabled us to assess the inhibitory tone from hypothalamic dopamine neurons on PRL secretion. We used a dopamine D2 receptor antagonist to relieve pituitary lactotrophs from the tuberoinfundibular dopaminergic inhibitory tone and demonstrate a D2-induced PRL rise that can be used to evaluate both the secretory capacity of lactotrophs and the magnitude of the inhibitory tone on pituitary PRL release. We demonstrate that, although lactotroph function is altered to enhance chronic PRL output, their secretory response to acute stimulus is not modified during lactation and that chronic hyperprolactinemia is linked to a lower inhibitory tone. The combination of a sensitive PRL ELISA and administration of D2 receptor antagonist provide a unique opportunity to investigate the function and plasticity of the lactotroph axis in freely moving mice.

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