scholarly journals Glutamatergic Tuning of Hyperactive Striatal Projection Neurons Controls the Motor Response to Dopamine Replacement in Parkinsonian Primates

Cell Reports ◽  
2018 ◽  
Vol 22 (4) ◽  
pp. 941-952 ◽  
Author(s):  
Arun Singh ◽  
Meagan A. Jenkins ◽  
Kenneth J. Burke ◽  
Goichi Beck ◽  
Andrew Jenkins ◽  
...  
Keyword(s):  
Motor Response ◽  
Projection Neurons ◽  
Striatal Projection Neurons

scholarly journals Role of striatal ΔFosB in l-Dopa–induced dyskinesias of parkinsonian nonhuman primates

2019 ◽  
Vol 116 (37) ◽  
pp. 18664-18672 ◽  
Author(s):  
Goichi Beck ◽  
Arun Singh ◽  
Jie Zhang ◽  
Lisa F. Potts ◽  
Jong-Min Woo ◽  
...  
Keyword(s):  
Motor Response ◽  
Nonhuman Primates ◽  
Firing Frequency ◽  
Projection Neurons ◽  
Neuronal Responses ◽  
Motor Responses ◽  
Striatal Projection Neurons ◽  
Adaptive Mechanisms

Long-term dopamine (DA) replacement therapy in Parkinson’s disease (PD) leads to the development of abnormal involuntary movements known asl-Dopa–induced dyskinesia (LID). The transcription factor ΔFosB that is highly up-regulated in the striatum following chronicl-Dopa exposure may participate in the mechanisms of altered neuronal responses to DA generating LID. To identify intrinsic effects of elevated ΔFosB onl-Dopa responses, we induced transgenic ΔFosB overexpression in the striatum of parkinsonian nonhuman primates kept naïve ofl-Dopa treatment. Elevated ΔFosB levels led to consistent appearance of LID since the initial acutel-Dopa tests. In line with this motor response, striatal projection neurons (SPNs) responded to DA with changes in firing frequency that reversed at the peak of the motor response, and these unstable SPN activity changes in response to DA are typically associated with the emergence of LID. Transgenic ΔFosB overexpression also induced up-regulation of other molecular markers of LID. These results support an autonomous role of striatal ΔFosB in the adaptive mechanisms altering motor responses to chronic DA replacement in PD.

scholarly journals Inhibition of Phosphodiesterase 10A Increases the Responsiveness of Striatal Projection Neurons to Cortical Stimulation

2008 ◽  
Vol 328 (3) ◽  
pp. 785-795 ◽  
Author(s):  
Sarah Threlfell ◽  
Stephen Sammut ◽  
Frank S. Menniti ◽  
Christopher J. Schmidt ◽  
Anthony R. West
Keyword(s):  
Cortical Stimulation ◽  
Projection Neurons ◽  
Striatal Projection Neurons ◽  
Phosphodiesterase 10A

Differences in synaptic integration between direct and indirect striatal projection neurons: Role of CaV 3 channels

Synapse ◽  
2018 ◽  
Vol 73 (4) ◽  
pp. e22079 ◽  
Author(s):  
Brisa García-Vilchis ◽  
Paola Suárez ◽  
Miguel Serrano-Reyes ◽  
Mario Arias-García ◽  
Dagoberto Tapia ◽  
...  
Keyword(s):  
Synaptic Integration ◽  
Projection Neurons ◽  
Striatal Projection 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.

scholarly journals What is the true discharge rate and pattern of the striatal projection neurons in Parkinson’s disease and Dystonia?

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Dan Valsky ◽  
Shai Heiman Grosberg ◽  
Zvi Israel ◽  
Thomas Boraud ◽  
Hagai Bergman ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Cluster Analysis ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Discharge Rate ◽  
Spontaneous Discharge ◽  
Projection Neurons ◽  
Pathological State ◽  
Striatal Projection Neurons ◽  
Deep Brain

Dopamine and striatal dysfunctions play a key role in the pathophysiology of Parkinson’s disease (PD) and Dystonia, but our understanding of the changes in the discharge rate and pattern of striatal projection neurons (SPNs) remains limited. Here, we recorded and examined multi-unit signals from the striatum of PD and dystonic patients undergoing deep brain stimulation surgeries. Contrary to earlier human findings, we found no drastic changes in the spontaneous discharge of the well-isolated and stationary SPNs of the PD patients compared to the dystonic patients or to the normal levels of striatal activity reported in healthy animals. Moreover, cluster analysis using SPN discharge properties did not characterize two well-separated SPN subpopulations, indicating no SPN subpopulation-specific (D1 or D2 SPNs) discharge alterations in the pathological state. Our results imply that small to moderate changes in spontaneous SPN discharge related to PD and Dystonia are likely amplified by basal ganglia downstream structures.

Muscarinic presynaptic modulation in GABAergic pallidal synapses of the rat

2015 ◽  
Vol 113 (3) ◽  
pp. 796-807 ◽  
Author(s):  
Ricardo Hernández-Martínez ◽  
José J. Aceves ◽  
Pavel E. Rueda-Orozco ◽  
Teresa Hernández-Flores ◽  
Omar Hernández-González ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Projection Neurons ◽  
Quantal Content ◽  
Short Term ◽  
Paired Pulse ◽  
Short Term Plasticity ◽  
Striatal Projection Neurons ◽  
Muscarinic Cholinergic ◽  
Muscarinic Modulation

The external globus pallidus (GPe) is central for basal ganglia processing. It expresses muscarinic cholinergic receptors and receives cholinergic afferents from the pedunculopontine nuclei (PPN) and other regions. The role of these receptors and afferents is unknown. Muscarinic M1-type receptors are expressed by synapses from striatal projection neurons (SPNs). Because axons from SPNs project to the GPe, one hypothesis is that striatopallidal GABAergic terminals may be modulated by M1 receptors. Alternatively, some M1 receptors may be postsynaptic in some pallidal neurons. Evidence of muscarinic modulation in any of these elements would suggest that cholinergic afferents from the PPN, or other sources, could modulate the function of the GPe. In this study, we show this evidence using striatopallidal slice preparations: after field stimulation in the striatum, the cholinergic muscarinic receptor agonist muscarine significantly reduced the amplitude of inhibitory postsynaptic currents (IPSCs) from synapses that exhibited short-term synaptic facilitation. This inhibition was associated with significant increases in paired-pulse facilitation, and quantal content was proportional to IPSC amplitude. These actions were blocked by atropine, pirenzepine, and mamba toxin-7, suggesting that receptors involved were M1. In addition, we found that some pallidal neurons have functional postsynaptic M1 receptors. Moreover, some evoked IPSCs exhibited short-term depression and a different kind of modulation: they were indirectly modulated by muscarine via the activation of presynaptic cannabinoid CB1 receptors. Thus pallidal synapses presenting distinct forms of short-term plasticity were modulated differently.

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