scholarly journals Sex-specific involvement of indirect-pathway medium spiny neurons in behavioral alteration of 16p11.2 hemi-deletion mouse model

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S494
Author(s):  
Jaekyoon Kim ◽  
Christopher Angelakos ◽  
Joseph Linch ◽  
Sarah Ferri ◽  
Ted Abel
Keyword(s):  
Mouse Model ◽  
Medium Spiny Neurons ◽  
Indirect Pathway ◽  
Behavioral Alteration ◽  
Spiny Neurons

scholarly journals Levodopa-Induced Dyskinesia Is Related to Indirect Pathway Medium Spiny Neuron Excitotoxicity: A Hypothesis Based on an Unexpected Finding

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Svetlana A. Ivanova ◽  
Anton J. M. Loonen
Keyword(s):  
Oxidative Stress ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Age Of Onset ◽  
Medium Spiny Neuron ◽  
Synaptic Membrane ◽  
Medium Spiny Neurons ◽  
Unexpected Finding ◽  
Indirect Pathway ◽  
Spiny Neurons

A serendipitous pharmacogenetic finding links the vulnerability to developing levodopa-induced dyskinesia to the age of onset of Huntington’s disease. Huntington’s disease is caused by a polyglutamate expansion of the protein huntingtin. Aberrant huntingtin is less capable of binding to a member of membrane-associated guanylate kinase family (MAGUKs): postsynaptic density- (PSD-) 95. This leaves more PSD-95 available to stabilize NR2B subunit carrying NMDA receptors in the synaptic membrane. This results in increased excitotoxicity for which particularly striatal medium spiny neurons from the indirect extrapyramidal pathway are sensitive. In Parkinson’s disease the sensitivity for excitotoxicity is related to increased oxidative stress due to genetically determined abnormal metabolism of dopamine or related products. This probably also increases the sensitivity of medium spiny neurons for exogenous levodopa. Particularly the combination of increased oxidative stress due to aberrant dopamine metabolism, increased vulnerability to NMDA induced excitotoxicity, and the particular sensitivity of indirect pathway medium spiny neurons for this excitotoxicity may explain the observed increased prevalence of levodopa-induced dyskinesia.

P.0733 Ensemble dynamics of the direct and indirect pathways of medium spiny neurons in a freely moving DYT-TOR1A dystonic mouse model

2021 ◽  
Vol 53 ◽  
pp. S535-S536
Author(s):  
F. França de Barros ◽  
M.D. Mendonça ◽  
S. Knorr ◽  
L. Rauschenberger ◽  
C.W. Ip ◽  
...  
Keyword(s):  
Mouse Model ◽  
Medium Spiny Neurons ◽  
Spiny Neurons ◽  
Freely Moving

New insights into the mechanism of drug-induced dyskinesia

CNS Spectrums ◽  
2012 ◽  
Vol 18 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Anton J. M. Loonen ◽  
Svetlana A. Ivanova
Keyword(s):  
Antipsychotic Drugs ◽  
Term Treatment ◽  
Medium Spiny Neurons ◽  
Indirect Pathway ◽  
Drug Induced ◽  
Disease Research ◽  
Spiny Neurons ◽  
Long Term Treatment ◽  
Cortical Circuit

Dyskinesia is an extrapyramidal movement disorder characterized by involuntary, repetitive, irregular motions that affect the mouth and face and/or the limbs and trunk. Tardive dyskinesia (TD) is a well-known complication of long-term treatment with antipsychotic drugs. Dyskinesia is also induced with levodopa, a treatment for Parkinson's disease, and it occurs spontaneously as a symptom of Huntington's disease. Research on the pathogenesis of TD has focused on a dysfunction of either the dopaminergic or serotonergic system. However, recent evidence has suggested that we should focus on the possible damage of GABAergic medium spiny neurons (MSNs). MSNs are the first station in the cortico-striato-thalamo-cortical circuit that regulates the amplitude and velocity of movements. Two pathways can be distinguished in this circuit: a direct pathway, which increases movements (hyperkinesia), and an indirect pathway, which decreases movements (hypokinesia). Both pathways are activated by glutamatergic corticostriatal neurons. Here, we discuss some evidence that supports the hypothesis that indirect pathway MSNs are damaged in dyskinesia.

scholarly journals Direct and Indirect Pathway Neurons in Ventrolateral Striatum Differentially Regulate Licking Movement and Nigral Responses

2021 ◽  
Author(s):  
Zhaorong Chen ◽  
Zhi-Yu Zhang ◽  
Taorong Xie ◽  
Wen Zhang ◽  
Yaping Li ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Rate Increase ◽  
Drinking Behavior ◽  
Medium Spiny Neurons ◽  
Indirect Pathway ◽  
Related Activity ◽  
Tongue Protrusion ◽  
D1 And D2 Receptors ◽  
Spiny Neurons ◽  
Output Neurons

SUMMARYDrinking behavior in rodents is characterized by stereotyped, rhythmic licking movement, which is regulated by the basal ganglia. It is unclear how direct and indirect pathways control the lick bout and individual lick event. We find that inactivating D1 and D2 receptors-expressing medium spiny neurons (MSNs) in the ventrolateral striatum (VLS) oppositely alters the number of licks in a bout. D1- and D2-MSNs exhibit similar patterns of lick sequence-related activity but different phases of oscillation time-locked to the lick cycle. On timescale of a lick cycle, transient inactivation of D1-MSNs during tongue protrusion reduces lick probability, whereas transient inactivation of D2-MSNs has no effect. On timescale of a lick bout, inactivation of D1-MSNs (D2-MSNs) causes rate increase (decrease) in a subset of basal ganglia output neurons that decrease firing during licking. Our results reveal the distinct roles of D1- and D2-MSNs in regulating licking at both coarse and fine timescales.

scholarly journals Transcriptional Diversity of Medium Spiny Neurons in the Primate Striatum

2020 ◽  
Author(s):  
Jing He ◽  
Michael Kleyman ◽  
Jianjiao Chen ◽  
Aydin Alikaya ◽  
Kathryn M. Rothenhoefer ◽  
...  
Keyword(s):  
Dorsal Striatum ◽  
Cell Types ◽  
Specific Information ◽  
Medium Spiny Neurons ◽  
Striatal Neurons ◽  
Cell Type ◽  
Indirect Pathway ◽  
Spiny Neurons ◽  
Single Nucleus ◽  
Cell Type Specific

AbstractThe striatum is the neural interface between dopamine reward signals and cortico-basal ganglia circuits responsible for value assignments, decisions, and actions. Medium spiny neurons (MSNs) make up the vast majority of striatal neurons and are traditionally classified as two distinct types: direct- and indirect-pathway MSNs. The direct- and indirect-pathway model has been useful for understanding some aspects of striatal functions, but it accounts for neither the anatomical heterogeneity, nor the functional diversity of the striatum. Here, we use single nucleus RNA-sequencing and Fluorescent In-Situ Hybridization to explore MSN diversity in the Rhesus macaque striatum. We identified MSN subtypes that correspond to the major subdivisions of the striatum. These include dorsal striatum subtypes associated with striosome and matrix compartments, as well as ventral striatum subtypes associated with the shell of the nucleus accumbens. We also describe a cell type that is anatomically restricted to “Neurochemically Unique Domains in the Accumbens and Putamen (NUDAPs)”. Together, these results help to advance nonhuman primate studies into the genomics era. The identified cell types provide a comprehensive blueprint for investigating cell type-specific information processing, and the differentially expressed genes lay a foundation for achieving cell type-specific transgenesis in the primate striatum.

scholarly journals Direct pathway neurons in mouse dorsolateral striatum in vivo receive stronger synaptic input than indirect pathway neurons

2019 ◽  
Vol 122 (6) ◽  
pp. 2294-2303 ◽  
Author(s):  
Marko Filipović ◽  
Maya Ketzef ◽  
Ramon Reig ◽  
Ad Aertsen ◽  
Gilad Silberberg ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Basal Ganglia ◽  
Medium Spiny Neurons ◽  
Indirect Pathway ◽  
Potential Fluctuations ◽  
Direct Pathway ◽  
Spiny Neurons ◽  
Total Input ◽  
Membrane Potential Fluctuations

Striatal projection neurons, the medium spiny neurons (MSNs), play a crucial role in various motor and cognitive functions. MSNs express either D1- or D2-type dopamine receptors and initiate the direct-pathway (dMSNs) or indirect pathways (iMSNs) of the basal ganglia, respectively. dMSNs have been shown to receive more inhibition than iMSNs from intrastriatal sources. Based on these findings, computational modeling of the striatal network has predicted that under healthy conditions dMSNs should receive more total input than iMSNs. To test this prediction, we analyzed in vivo whole cell recordings from dMSNs and iMSNs in healthy and dopamine-depleted (6OHDA) anaesthetized mice. By comparing their membrane potential fluctuations, we found that dMSNs exhibited considerably larger membrane potential fluctuations over a wide frequency range. Furthermore, by comparing the spike-triggered average membrane potentials, we found that dMSNs depolarized toward the spike threshold significantly faster than iMSNs did. Together, these findings (in particular the STA analysis) corroborate the theoretical prediction that direct-pathway MSNs receive stronger total input than indirect-pathway neurons. Finally, we found that dopamine-depleted mice exhibited no difference between the membrane potential fluctuations of dMSNs and iMSNs. These data provide new insights into the question of how the lack of dopamine may lead to behavioral deficits associated with Parkinson’s disease. NEW & NOTEWORTHY The direct and indirect pathways of the basal ganglia originate from the D1- and D2-type dopamine receptor expressing medium spiny neurons (dMSNs and iMSNs). Theoretical results have predicted that dMSNs should receive stronger synaptic input than iMSNs. Using in vivo intracellular membrane potential data, we provide evidence that dMSNs indeed receive stronger input than iMSNs, as has been predicted by the computational model.

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