Faculty Opinions recommendation of The distinct role of medium spiny neurons and cholinergic interneurons in the D₂/A₂A receptor interaction in the striatum: implications for Parkinson's disease.

2011 ◽  
Author(s):  
D James Surmeier
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Receptor Interaction ◽  
Medium Spiny Neurons ◽  
Cholinergic Interneurons ◽  
Spiny Neurons ◽  
Distinct Role

Ultrastructure of Striatal Dopamine Synapses in Rats with Striatal Dopamine Depletion

2001 ◽  
Vol 7 (S2) ◽  
pp. 660-661
Author(s):  
W. Gray (Jay) Jerome ◽  
Thomas J. Montine ◽  
Ariel Y. Deutch
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Striatal Dopamine ◽  
Medium Spiny Neurons ◽  
Dopamine Depletion ◽  
Proximate Cause ◽  
Spiny Neurons ◽  
Neuronal Reorganization ◽  
Striatal Dopamine Depletion ◽  
6 Hydroxydopamine

Parkinson's disease (PD) is characterized by rigidity, tremor, bradykinesia, and postural instability. The proximate cause of these symptoms is striatal dopamine (DA) insufficiency. The motor symptoms of PD can be alleviated by DA replacement therapy. However, late in the course of the disease patients appear to become less responsive to DA replacement. This therapeutic change suggests the possibility of structural and/or functional defects in striatal medium spiny neurons, which receive convergent DA and cortical (glutamate) inputs.To understand the neuronal reorganization occurring in Parkinson's disease, we used ultrastructural methods to examine the striatum of rats with striatal dopaminergic deafferentation induced by unilateral intranigral injection of 6-hydroxydopamine. After a six month survival, rats were deeply anesthetized with pentobarbital and perfused with 4% paraformaldehyde-1 % glutaraldehdyde solution in 0.1M Sorenson's phosphate buffer (pH 7.4). The brains were removed, post-fixed for 12 hours, embedded in paraffin, and coronal sections cut through the striatum and midbrain.

scholarly journals Role of 5-HT1A Receptor in Vilazodone-Mediated Suppression of L-DOPA-Induced Dyskinesia and Increased Responsiveness to Cortical Input in Striatal Medium Spiny Neurons in an Animal Model of Parkinson’s Disease

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5790
Author(s):  
Feras Altwal ◽  
Fernando E. Padovan-Neto ◽  
Alexandra Ritger ◽  
Heinz Steiner ◽  
Anthony R. West
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Partial Agonist ◽  
Critical Role ◽  
Medium Spiny Neurons ◽  
Cortical Input ◽  
Spiny Neurons ◽  
Underlying Mechanisms

L-DOPA therapy in Parkinson’s disease (PD) is limited due to emerging L-DOPA-induced dyskinesia. Research has identified abnormal dopamine release from serotonergic (5-HT) terminals contributing to this dyskinesia. Selective serotonin reuptake inhibitors (SSRIs) or 5-HT receptor (5-HTr) agonists can regulate 5-HT activity and attenuate dyskinesia, but they often also produce a loss of the antiparkinsonian efficacy of L-DOPA. We investigated vilazodone, a novel multimodal 5-HT agent with SSRI and 5-HTr1A partial agonist properties, for its potential to reduce dyskinesia without interfering with the prokinetic effects of L-DOPA, and underlying mechanisms. We assessed vilazodone effects on L-DOPA-induced dyskinesia (abnormal involuntary movements, AIMs) and aberrant responsiveness to corticostriatal drive in striatal medium spiny neurons (MSNs) measured with in vivo single-unit extracellular recordings, in the 6-OHDA rat model of PD. Vilazodone (10 mg/kg) suppressed all subtypes (axial, limb, orolingual) of AIMs induced by L-DOPA (5 mg/kg) and the increase in MSN responsiveness to cortical stimulation (shorter spike onset latency). Both the antidyskinetic effects and reversal in MSN excitability by vilazodone were inhibited by the 5-HTr1A antagonist WAY-100635, demonstrating a critical role for 5-HTr1A in these vilazodone actions. Our results indicate that vilazodone may serve as an adjunct therapeutic for reducing dyskinesia in patients with PD.

scholarly journals What Is the Role of Thalamostriatal Circuits in Learning Vocal Sequences?

2021 ◽  
Vol 15 ◽  
Author(s):  
Lei Xiao ◽  
Todd F. Roberts
Keyword(s):  
Reinforcement Learning ◽  
Song Learning ◽  
Medium Spiny Neurons ◽  
Cholinergic Interneurons ◽  
Related Information ◽  
Spiny Neurons ◽  
Motor Information ◽  
Area X ◽  
Reinforcement Learning Model

Basal ganglia (BG) circuits integrate sensory and motor-related information from the cortex, thalamus, and midbrain to guide learning and production of motor sequences. Birdsong, like speech, is comprised of precisely sequenced vocal elements. Learning song sequences during development relies on Area X, a vocalization related region in the medial striatum of the songbird BG. Area X receives inputs from cortical-like pallial song circuits and midbrain dopaminergic circuits and sends projections to the thalamus. It has recently been shown that thalamic circuits also send substantial projections back to Area X. Here, we outline a gated-reinforcement learning model for how Area X may use signals conveyed by thalamostriatal inputs to direct song learning. Integrating conceptual advances from recent mammalian and songbird literature, we hypothesize that thalamostriatal pathways convey signals linked to song syllable onsets and offsets and influence striatal circuit plasticity via regulation of cholinergic interneurons (ChIs). We suggest that syllable sequence associated vocal-motor information from the thalamus drive precisely timed pauses in ChIs activity in Area X. When integrated with concurrent corticostriatal and dopaminergic input, this circuit helps regulate plasticity on medium spiny neurons (MSNs) and the learning of syllable sequences. We discuss new approaches that can be applied to test core ideas of this model and how associated insights may provide a framework for understanding the function of BG circuits in learning motor sequences.

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