scholarly journals Dopaminergic Modulation of Lateral Amygdala Neuronal Activity: Differential D1 and D2 Receptor Effects on Thalamic and Cortical Afferent Inputs

2015 ◽  
Vol 18 (8) ◽  
pp. pyv015-pyv015 ◽  
Author(s):  
C.-h. Chang ◽  
A. A. Grace
Keyword(s):  
Neuronal Activity ◽  
D2 Receptor ◽  
Lateral Amygdala ◽  
Dopaminergic Modulation ◽  
Afferent Inputs

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.

Effects of Dopaminergic Modulation on the Integrative Properties of the Ventral Striatal Medium Spiny Neuron

2007 ◽  
Vol 98 (6) ◽  
pp. 3731-3748 ◽  
Author(s):  
Jason T. Moyer ◽  
John A. Wolf ◽  
Leif H. Finkel
Keyword(s):  
Neuronal Excitability ◽  
Time Window ◽  
Classical Model ◽  
D2 Receptor ◽  
Medium Spiny Neuron ◽  
Integration Time ◽  
Whole Cell ◽  
Functional Changes ◽  
Receptor Modulation ◽  
Dopaminergic Modulation

Dopaminergic modulation produces a variety of functional changes in the principal cell of the striatum, the medium spiny neuron (MSN). Using a 189-compartment computational model of a ventral striatal MSN, we simulated whole cell D1- and D2-receptor–mediated modulation of both intrinsic (sodium, calcium, and potassium) and synaptic currents (AMPA and NMDA). Dopamine (DA) modulations in the model were based on a review of published experiments in both ventral and dorsal striatum. To objectively assess the net effects of DA modulation, we combined reported individual channel modulations into either D1- or D2-receptor modulation conditions and studied them separately. Contrary to previous suggestions, we found that D1 modulation had no effect on MSN nonlinearity and could not induce bistability. In agreement with previous suggestions, we found that dopaminergic modulation leads to changes in input filtering and neuronal excitability. Importantly, the changes in neuronal excitability agree with the classical model of basal ganglia function. We also found that DA modulation can alter the integration time window of the MSN. Interestingly, the effects of DA modulation of synaptic properties opposed the effects of DA modulation of intrinsic properties, with the synaptic modulations generally dominating the net effect. We interpret this lack of synergy to suggest that the regulation of whole cell integrative properties is not the primary functional purpose of DA. We suggest that D1 modulation might instead primarily regulate calcium influx to dendritic spines through NMDA and L-type calcium channels, by both direct and indirect mechanisms.

Dopaminergic modulation of spontaneous inhibitory network activity in the lateral amygdala

2004 ◽  
Vol 47 (5) ◽  
pp. 631-639 ◽  
Author(s):  
Karin Lorétan ◽  
Stephanie Bissière ◽  
Andreas Lüthi
Keyword(s):  
Network Activity ◽  
Lateral Amygdala ◽  
Inhibitory Network ◽  
Dopaminergic Modulation

scholarly journals Dopaminergic modulation of human inter-temporal choice: a diffusion model analysis using the D2-receptor-antagonist haloperidol

2020 ◽  
Author(s):  
Ben Wagner ◽  
Mareike Clos ◽  
Tobias Sommer ◽  
Jan Peters
Keyword(s):  
Receptor Antagonist ◽  
Diffusion Model ◽  
D2 Receptor ◽  
Temporal Discounting ◽  
Reward Processing ◽  
Drift Diffusion ◽  
Model Free ◽  
Dopaminergic Modulation ◽  
Inhibitory Feedback ◽  
Decision Times

AbstractThe neurotransmitter dopamine is implicated in diverse functions, including reward processing, reinforcement learning and cognitive control. The tendency to discount future rewards in value over time has long been discussed in the context of potential dopaminergic modulation. Here we examined the effect of a single dose of the D2 receptor antagonist Haloperidol (2mg) on temporal discounting. Our approach extends previous human pharmacological studies in two ways. First, we applied state-of-the-art computational modeling based on the drift diffusion model to comprehensively examine choice dynamics. Second, we examined dopaminergic modulation of reward magnitude effects on temporal discounting. Drift diffusion modeling revealed reduced temporal discounting and substantially faster non-decision times under Haloperidol. Temporal discounting was substantially increased for low vs. high reward magnitudes, but this magnitude effect was largely unaffected by Haloperidol. These results were corroborated by model-free analyses as well as modeling via more standard approaches using softmax action selection. We previously reported elevated caudate activation under Haloperidol in this sample of participants, supporting the idea that Haloperidol elevated dopamine neurotransmission, e.g. by blocking inhibitory feedback via presynaptic D2 autoreceptors. The present modeling results show that during inter-temporal choice, this leads to attenuated temporal discounting and increased response vigor (shorter non-decision times).

scholarly journals Dopamine Reduces Odor- and Elevated-K+-Induced Calcium Responses in Mouse Olfactory Receptor Neurons In Situ

2004 ◽  
Vol 91 (4) ◽  
pp. 1492-1499 ◽  
Author(s):  
Colleen C. Hegg ◽  
Mary T. Lucero
Keyword(s):  
Receptor Antagonist ◽  
Dopamine Receptor ◽  
Olfactory Receptor ◽  
D2 Receptor ◽  
Olfactory Receptor Neurons ◽  
D2 Dopamine Receptor ◽  
Dopamine Receptor Antagonist ◽  
Voltage Gated ◽  
Dopaminergic Modulation ◽  
Receptor Neurons

Although D2 dopamine receptors have been localized to olfactory receptor neurons (ORNs) and dopamine has been shown to modulate voltage-gated ion channels in ORNs, dopaminergic modulation of either odor responses or excitability in mammalian ORNs has not previously been demonstrated. We found that <50 μM dopamine reversibly suppresses odor-induced Ca2+ transients in ORNs. Confocal laser imaging of 300-μm-thick slices of neonatal mouse olfactory epithelium loaded with the Ca2+-indicator dye fluo-4 AM revealed that dopaminergic suppression of odor responses could be blocked by the D2 dopamine receptor antagonist sulpiride (<500 μM). The dopamine-induced suppression of odor responses was completely reversed by 100 μM nifedipine, suggesting that D2 receptor activation leads to an inhibition of L-type Ca2+ channels in ORNs. In addition, dopamine reversibly reduced ORN excitability as evidenced by reduced amplitude and frequency of Ca2+ transients in response to elevated K+, which activates voltage-gated Ca2+ channels in ORNs. As with the suppression of odor responses, the effects of dopamine on ORN excitability were blocked by the D2 dopamine receptor antagonist sulpiride (<500 μM). The observation of dopaminergic modulation of odor-induced Ca2+ transients in ORNs adds to the growing body of work showing that olfactory receptor neurons can be modulated at the periphery. Dopamine concentrations in nasal mucus increase in response to noxious stimuli, and thus D2 receptor-mediated suppression of voltage-gated Ca2+ channels may be a novel neuroprotective mechanism for ORNs.

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