scholarly journals L-DOPA-Induced Dyskinesia and Abnormal Signaling in Striatal Medium Spiny Neurons: Focus on Dopamine D1 Receptor-Mediated Transmission

2011 ◽  
Vol 5 ◽  
Author(s):  
Michael Feyder ◽  
Alessandra Bonito-Oliva ◽  
Gilberto Fisone
Keyword(s):  
Dopamine D1 Receptor ◽  
D1 Receptor ◽  
Medium Spiny Neurons ◽  
Spiny Neurons

scholarly journals Inhibitory ultrapotent chemogenetics activate dopamine D1 receptor-expressing medium spiny neurons

2020 ◽  
Author(s):  
Stephanie C. Gantz ◽  
Maria M. Ortiz ◽  
Andrew J. Belilos ◽  
Khaled Moussawi
Keyword(s):  
Brain Slices ◽  
Reversal Potential ◽  
Cell Types ◽  
Receptor Activation ◽  
Dopamine D1 Receptor ◽  
D1 Receptor ◽  
Medium Spiny Neurons ◽  
Inhibitory Function ◽  
Spiny Neurons

SUMMARYUltrapotent chemogenetics, including the chloride-permeable inhibitory PSAM4-GlyR receptor, were recently proposed as a powerful strategy to selectively control neuronal activity in awake, behaving animals. We aimed to validate the inhibitory function of PSAM4-GlyR in dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) in the ventral striatum. Activation of PSAM4-GlyR with the uPSEM792 ligand enhanced rather than suppressed the activity of D1-MSNs in vivo as indicated by increased c-fos expression in D1-MSNs. Whole-cell recordings in mouse brain slices showed that activation of PSAM4-GlyR did not inhibit firing of action potentials in D1-MSNs. Activation of PSAM4-GlyR depolarized D1-MSNs, attenuated GABAergic inhibition, and shifted the reversal potential of PSAM4-GlyR current to more depolarized potentials, perpetuating the depolarizing effect of receptor activation. The data show that ‘inhibitory’ PSAM4-GlyR chemogenetics may actually activate certain cell types, and highlight the pitfalls of utilizing chloride conductances to inhibit neurons.

scholarly journals Fronto-striatal projections regulate approach-avoidance conflict

2020 ◽  
Author(s):  
Adrienne C. Loewke ◽  
Adelaide R. Minerva ◽  
Alexandra B. Nelson ◽  
Anatol C. Kreitzer ◽  
Lisa A. Gunaydin
Keyword(s):  
Anxiety Disorders ◽  
Avoidance Behavior ◽  
D1 Receptor ◽  
Projection Neurons ◽  
Medium Spiny Neurons ◽  
Neural Pathways ◽  
Spiny Neurons ◽  
Striatal Projection Neurons ◽  
Neural Computations ◽  
Approach Avoidance

ABSTRACTThe dorsomedial prefrontal cortex (dmPFC) has been linked to approach-avoidance behavior and decision-making under conflict, key neural computations thought to be altered in anxiety disorders. However, the heterogeneity of efferent prefrontal projections has obscured identification of the specific top-down neural pathways regulating these anxiety-related behaviors. While the dmPFC-amygdala circuit has long been implicated in controlling reflexive fear responses, recent work suggests that this circuit is less important for avoidance behavior. We hypothesized that dmPFC neurons projecting to the dorsomedial striatum (DMS) represent a subset of prefrontal neurons that robustly encode and drive approach-avoidance behavior. Using fiber photometry recording during the elevated zero maze (EZM) task, we show heightened neural activity in prefrontal and fronto-striatal projection neurons, but not fronto-amydalar projection neurons, during exploration of the anxiogenic open arms of the maze. Additionally, through pathway-specific optogenetics we demonstrate that this fronto-striatal projection preferentially excites postsynaptic D1 receptor-expressing medium spiny neurons in the DMS and bidirectionally controls avoidance behavior. We conclude that this striatal-projecting subpopulation of prefrontal neurons regulates approach-avoidance conflict, supporting a model for prefrontal control of defensive behavior in which the dmPFC-amygdala projection controls reflexive fear behavior and the dmPFC-striatum projection controls anxious avoidance behavior. Our findings identify this fronto-striatal circuit as a valuable therapeutic target for developing interventions to alleviate excessive avoidance behavior in anxiety disorders.

Mechanisms of dopamine-mediated incentive learning

2018 ◽  
Author(s):  
Richard J. Beninger
Keyword(s):  
Dendritic Spines ◽  
D2 Receptor ◽  
D1 Receptor ◽  
Medium Spiny Neurons ◽  
Prediction Errors ◽  
Incentive Learning ◽  
Spiny Neurons ◽  
Negative Prediction ◽  
Response Systems ◽  
Subsequent Wave

Mechanisms of dopamine-mediated incentive learning explains how sensory events, resulting from an animal’s movement and the environment, activate cortical glutamatergic projections to dendritic spines of striatal medium spiny neurons to initiate a wave of phosphorylation. If no rewarding stimulus is encountered, a subsequent wave of phosphatase activity undoes the phosphorylation. If a rewarding stimulus is encountered, dopamine initiates a cascade of events in D1 receptor-expressing medium spiny neurons that may prevent the phosphatase effects and work synergistically with signaling events produced by glutamate. As a result, corticostriatal synapses have a greater impact on response systems; this may be part of the mechanism of incentive learning. Dopamine acting on dendritic spines of D2 receptor-expressing medium spiny neurons may prevent synaptic strengthening by inhibiting adenosine signaling; these synapses may be weakened through mechanisms involving endocannabinoids. When dopamine concentrations drop, e.g. during negative prediction errors, the opposite may occur, producing inverse incentive learning.

scholarly journals Restoration of KCC2 Membrane Localization in Striatal Dopamine D2 Receptor-Expressing Medium Spiny Neurons Rescues Locomotor Deficits in HIV Tat-Transgenic Mice

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110220
Author(s):  
Aaron J. Barbour ◽  
Sara R. Nass ◽  
Yun K. Hahn ◽  
Kurt F. Hauser ◽  
Pamela E. Knapp
Keyword(s):  
Transgenic Mice ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Brain Regions ◽  
D1 Receptor ◽  
Membrane Localization ◽  
Hippocampal Damage ◽  
Medium Spiny Neurons ◽  
Dopamine D2 ◽  
Spiny Neurons

People infected with HIV (PWH) are highly susceptible to striatal and hippocampal damage. Motor and memory impairments are common among these patients, likely as behavioral manifestations of damage to these brain regions. GABAergic dysfunction from HIV infection and viral proteins such as transactivator of transcription (Tat) have been well documented. We recently demonstrated that the neuron specific Cl− extruder, K+ Cl− cotransporter 2 (KCC2), is diminished after exposure to HIV proteins, including Tat, resulting in disrupted GABAAR-mediated hyperpolarization and inhibition. Here, we utilized doxycycline (DOX)-inducible, GFAP-driven HIV-1 Tat transgenic mice to further explore this phenomenon. After two weeks of Tat expression, we found no changes in hippocampal KCC2 levels, but a significant decrease in the striatum that was associated with hyperlocomotion in the open field assay. We were able to restore KCC2 activity and baseline locomotion with the KCC2 enhancer, CLP290. Additionally, we found that CLP290, whose mechanism of action has yet to be described, acts to restore phosphorylation of serine 940 resulting in increased KCC2 membrane localization. We also examined neuronal subpopulation contributions to the noted effects and found significant differences. Dopamine D2 receptor-expressing medium spiny neurons (MSNs) were selectively vulnerable to Tat-induced KCC2 loss, with no changes observed in dopamine D1 receptor-expressing MSNs. These results suggest that disinhibition/diminished hyperpolarization of dopamine D2 receptor-expressing MSNs can manifest as increased locomotion in this context. They further suggest that KCC2 activity might be a therapeutic target to alleviate motor disturbances related to HIV.

Nicotine-induced and D1-receptor-dependent dendritic remodeling in a subset of dorsolateral striatum medium spiny neurons

Neuroscience ◽  
2017 ◽  
Vol 356 ◽  
pp. 242-254 ◽  
Author(s):  
Daniel G. Ehlinger ◽  
Julian C. Burke ◽  
Craig G. McDonald ◽  
Robert F. Smith ◽  
Hadley C. Bergstrom
Keyword(s):  
D1 Receptor ◽  
Medium Spiny Neurons ◽  
Dorsolateral Striatum ◽  
Spiny Neurons

scholarly journals Opposing roles for striatonigral and striatopallidal neurons in dorsolateral striatum in consolidating new instrumental actions

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexander C. W. Smith ◽  
Sietse Jonkman ◽  
Alexandra G. Difeliceantonio ◽  
Richard M. O’Connor ◽  
Soham Ghoshal ◽  
...  
Keyword(s):  
Lever Press ◽  
D1 Receptor ◽  
Protein Synthesis Inhibitor ◽  
Medium Spiny Neurons ◽  
Synthesis Inhibitor ◽  
Consolidation Process ◽  
Dorsolateral Striatum ◽  
Spiny Neurons ◽  
New Learning ◽  
The Brain

AbstractComparatively little is known about how new instrumental actions are encoded in the brain. Using whole-brain c-Fos mapping, we show that neural activity is increased in the anterior dorsolateral striatum (aDLS) of mice that successfully learn a new lever-press response to earn food rewards. Post-learning chemogenetic inhibition of aDLS disrupts consolidation of the new instrumental response. Similarly, post-learning infusion of the protein synthesis inhibitor anisomycin into the aDLS disrupts consolidation of the new response. Activity of D1 receptor-expressing medium spiny neurons (D1-MSNs) increases and D2-MSNs activity decreases in the aDLS during consolidation. Chemogenetic inhibition of D1-MSNs in aDLS disrupts the consolidation process whereas D2-MSN inhibition strengthens consolidation but blocks the expression of previously learned habit-like responses. These findings suggest that D1-MSNs in the aDLS encode new instrumental actions whereas D2-MSNs oppose this new learning and instead promote expression of habitual actions.

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