Levodopa Causes Striatal Cholinergic Interneuron Burst‐Pause Activity in Parkinsonian Mice

2021 ◽  
Author(s):  
Rodrigo Manuel Paz ◽  
Cecilia Tubert ◽  
Agostina Monica Stahl ◽  
Yimy Amarillo ◽  
Lorena Rela ◽  
...  
Keyword(s):  
Cholinergic Interneuron

Two Neuropeptides Colocalized in a Command-Like Neuron Use Distinct Mechanisms to Enhance Its Fast Synaptic Connection

2003 ◽  
Vol 90 (3) ◽  
pp. 2074-2079 ◽  
Author(s):  
H.-Y. Koh ◽  
F. S. Vilim ◽  
J. Jing ◽  
K. R. Weiss
Keyword(s):  
High Frequency ◽  
Synaptic Connection ◽  
Quantal Content ◽  
Functional Consequence ◽  
Functional Implication ◽  
Quantal Size ◽  
Quantal Analysis ◽  
Cholinergic Interneuron ◽  
Single Synapse ◽  
Stimulation Of

In many neurons more than one peptide is colocalized with a classical neurotransmitter. The functional consequence of such an arrangement has been rarely investigated. Here, within the feeding circuit of Aplysia, we investigate at a single synapse the actions of two modulatory neuropeptides that are present in a cholinergic interneuron. In combination with previous work, our study shows that the command-like neuron for feeding, CBI-2, contains two neuropeptides, feeding circuit activating peptide (FCAP) and cerebral peptide 2 (CP2). Previous studies showed that high-frequency prestimulation or repeated stimulation of CBI-2 increases the size of CBI-2 to B61/62 excitatory postsynaptic potentials (EPSPs) and shortens the latency of firing of neuron B61/62 in response to CBI-2 stimulation. We find that both FCAP and CP2 mimic these two effects. The variance method of quantal analysis indicates that FCAP increases the calculated quantal size ( q) and CP2 increases the calculated quantal content ( m) of EPSPs. Since the PSP amplitude represents the product of q and m, the joint action of the two peptides is expected to be cooperative. This observation suggests a possible functional implication for multiple neuropeptides colocalized with a classical neurotransmitter in one neuron.

scholarly journals Dopamine Deficiency Reduces Striatal Cholinergic Interneuron Function in Models of Parkinson’s Disease

Neuron ◽  
2019 ◽  
Vol 103 (6) ◽  
pp. 1056-1072.e6 ◽  
Author(s):  
Jonathan W. McKinley ◽  
Ziqing Shi ◽  
Ivana Kawikova ◽  
Matthew Hur ◽  
Ian J. Bamford ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cholinergic Interneuron

scholarly journals Decrease of a Current Mediated by K v 1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism

Cell Reports ◽  
2016 ◽  
Vol 16 (10) ◽  
pp. 2749-2762 ◽  
Author(s):  
Cecilia Tubert ◽  
Irene R.E. Taravini ◽  
Eden Flores-Barrera ◽  
Gonzalo M. Sánchez ◽  
María Alejandra Prost ◽  
...  
Keyword(s):  
Experimental Parkinsonism ◽  
Cholinergic Interneuron ◽  
A Current

scholarly journals Striatal cholinergic interneuron numbers are increased in a rodent model of dystonic cerebral palsy

2020 ◽  
Author(s):  
Sushma Gandham ◽  
Yearam Tak ◽  
Bhooma R. Aravamuthan
Keyword(s):  
Cerebral Palsy ◽  
Brain Injury ◽  
Movement Disorder ◽  
Rodent Model ◽  
Gabaergic Interneuron ◽  
Neonatal Brain ◽  
Common Cause ◽  
Neonatal Brain Injury ◽  
Unbiased Stereology ◽  
Cholinergic Interneuron

AbstractNeonatal brain injury leading to cerebral palsy (CP) is the most common cause of childhood dystonia, a painful and functionally debilitating movement disorder. Rare monogenic etiologies of dystonia have been associated with striatal cholinergic interneuron (ChI) pathology. However it is unclear whether striatal ChI pathology is also associated with dystonia following neonatal brain injury. We used unbiased stereology to estimate striatal ChI and parvalbumin-positive GABAergic interneuron (PVI) numbers in a rodent model of neonatal brain injury that demonstrates electrophysiological markers of dystonia and spasticity. Striatal ChI numbers are increased following neonatal brain injury while PVI numbers are unchanged. These numbers do not correlate with electrophysiologic measures of dystonia severity. This suggests that striatal ChI pathology, though present, may not be the primary pathophysiologic contributor to dystonia following neonatal brain injury. Increased striatal ChI numbers could instead represent a passenger or protective phenomenon in the setting of dystonic CP.

scholarly journals Alterations in the intrinsic properties of striatal cholinergic interneurons after dopamine lesion and chronic L-DOPA

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Se Joon Choi ◽  
Thong C Ma ◽  
Yunmin Ding ◽  
Timothy Cheung ◽  
Neal Joshi ◽  
...  
Keyword(s):  
Normal Activity ◽  
Sk Channels ◽  
Intrinsic Properties ◽  
Therapeutic Approaches ◽  
Physiological Basis ◽  
Cholinergic Interneurons ◽  
Pharmacological Blockade ◽  
Cholinergic Interneuron ◽  
Spontaneous Firing Rate ◽  
Small Conductance

Changes in striatal cholinergic interneuron (ChI) activity are thought to contribute to Parkinson’s disease pathophysiology and dyskinesia from chronic L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, but the physiological basis of these changes is unknown. We find that dopamine lesion decreases the spontaneous firing rate of ChIs, whereas chronic treatment with L-DOPA of lesioned mice increases baseline ChI firing rates to levels beyond normal activity. The effect of dopamine loss on ChIs was due to decreased currents of both hyperpolarization-activated cyclic nucleotide-gated (HCN) and small conductance calcium-activated potassium (SK) channels. L-DOPA reinstatement of dopamine normalized HCN activity, but SK current remained depressed. Pharmacological blockade of HCN and SK activities mimicked changes in firing, confirming that these channels are responsible for the molecular adaptation of ChIs to dopamine loss and chronic L-DOPA treatment. These findings suggest that targeting ChIs with channel-specific modulators may provide therapeutic approaches for alleviating L-DOPA-induced dyskinesia in PD patients.

Cholinergic Interneuron and Parkinsonism

2008 ◽  
pp. 1-11
Author(s):  
Dario Cuomo ◽  
Paola Platania ◽  
Giuseppina Martella ◽  
Graziella Madeo ◽  
Giuseppe Sciamanna ◽  
...  
Keyword(s):  
Cholinergic Interneuron

Acetylcholine receptor binding and cholinergic interneuron density are unaltered in a genetic animal model of primary paroxysmal dystonia

2006 ◽  
Vol 1099 (1) ◽  
pp. 176-182 ◽  
Author(s):  
Melanie Hamann ◽  
Roger Raymond ◽  
Suneel Varughesi ◽  
José N. Nobrega ◽  
Angelika Richter
Keyword(s):  
Animal Model ◽  
Acetylcholine Receptor ◽  
Receptor Binding ◽  
Genetic Animal Model ◽  
Cholinergic Interneuron ◽  
Paroxysmal Dystonia

scholarly journals Alterations in the intrinsic properties of striatal cholinergic interneurons after dopamine lesion and chronic L-DOPA

2020 ◽  
Author(s):  
Se Joon Choi ◽  
Thong C. Ma ◽  
Yunmin Ding ◽  
Timothy Cheung ◽  
Neal Joshi ◽  
...  
Keyword(s):  
Normal Activity ◽  
Sk Channels ◽  
Intrinsic Properties ◽  
Therapeutic Approaches ◽  
Physiological Basis ◽  
Cholinergic Interneurons ◽  
Pharmacological Blockade ◽  
Cholinergic Interneuron ◽  
Spontaneous Firing Rate ◽  
Small Conductance

SummaryChanges in striatal cholinergic interneuron (ChI) activity are thought to contribute to Parkinson’s disease pathophysiology and dyskinesia from chronic L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, but the physiological basis of these changes are unknown. We find that dopamine lesion decreases the spontaneous firing rate of ChIs, whereas chronic treatment with L-DOPA of lesioned mice increases baseline ChI firing rates to levels beyond normal activity. The effect of dopamine loss on ChIs was due to decreased currents of both hyperpolarization-activated cyclic nucleotide-gated (HCN) and small conductance calcium-activated potassium (SK) channels. L-DOPA reinstatement of dopamine normalized HCN activity, but SK current remained depressed. Pharmacological blockade of HCN and SK activities mimicked changes in firing, confirming that these channels are responsible for the molecular adaptation of ChIs to dopamine loss and chronic L-DOPA treatment. These findings suggest that targeting ChIs with channel-specific modulators may provide therapeutic approaches for alleviating L-DOPA-induced dyskinesia in PD patients.

scholarly journals Cholinergic interneuron characteristics and nicotinic properties in the striatum

2002 ◽  
Vol 53 (4) ◽  
pp. 590-605 ◽  
Author(s):  
Fu-Ming Zhou ◽  
Charles J. Wilson ◽  
John A. Dani
Keyword(s):  
Cholinergic Interneuron
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