Related Experiment Video
Updated: Apr 26, 2026
08:27
Single Synapse Indicators of Glutamate Release and Uptake in Acute Brain Slices from Normal and Huntington Mice
Published on: March 11, 2020
5.6K
Functional Differences Between Direct and Indirect Striatal Output Pathways in Huntington's Disease.
Laurie Galvan1, Véronique M André1, Elizabeth A Wang1
1Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior and the Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Journal of Huntington'S Disease
|July 27, 2014
Summary
Huntington's disease (HD) alters medium-sized spiny neurons (MSNs) in the striatum. Direct pathway MSNs show early increases in excitatory and inhibitory inputs, impacting brain function.
Area of Science:
- Neuroscience
- Neurodegenerative Diseases
- Molecular Biology
Background:
- Huntington's disease (HD) exhibits differential alterations in striatal medium-sized spiny neurons (MSNs) of direct and indirect pathways.
- Indirect pathway MSNs are particularly vulnerable in HD, with early marker loss observed in postmortem brains and mouse models.
- Direct pathway MSNs appear relatively spared in early stages, though functional alterations are difficult to discern due to morphological similarities.
Purpose of the Study:
- To investigate the functional alterations in direct and indirect pathway MSNs in Huntington's disease models.
- To elucidate the time-dependent changes in synaptic inputs to MSNs in HD.
- To explore the influence of dopamine modulation on synaptic transmission in HD.
Main Methods:
- Utilized enhanced green fluorescent protein (EGFP) as a reporter to identify dopamine D1 (direct) and D2 (indirect) receptor-expressing MSNs.
- Examined synaptic function in identified MSNs within HD models.
- Investigated time-dependent changes in excitatory and inhibitory inputs.
Main Results:
- Demonstrated significant time-dependent alterations in the balance of excitatory and inhibitory inputs to both direct and indirect pathway MSNs in HD.
- Observed early increases in both excitatory and inhibitory inputs to direct pathway MSNs.
- Identified a strong influence of altered dopamine modulation on synaptic transmission in HD models.
Conclusions:
- The findings reveal significant changes in synaptic balance within striatal pathways in HD.
- Early alterations in direct pathway MSNs, including increased excitatory and inhibitory inputs, are highlighted.
- Altered dopamine modulation plays a crucial role in synaptic transmission changes in HD models, affecting output nuclei like the GPi and SNr.
Related Concept Videos
01:21Huntington Disease l: Introduction
68
Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show...
68
01:22Indirect Motor Pathways
3.4K
The indirect motor or extrapyramidal pathways originate in the brainstem, the lower portion of the brain that connects it to the spinal cord. They consist of several distinct tracts, each with specialized functions. The four main tracts of the indirect motor pathways are the vestibulospinal tract, the reticulospinal tract, the tectospinal tract, and the rubrospinal tract.
The vestibulospinal tract originates in the vestibular nuclei of the brainstem. The vestibular system detects changes in...
The vestibulospinal tract originates in the vestibular nuclei of the brainstem. The vestibular system detects changes in...
3.4K
01:11Direct Motor Pathways
4.7K
The direct motor pathways, also known as the pyramidal tracts, are a group of neural pathways that originate in the brain and descend through the spinal cord. They control the voluntary movement of the body. There are two major direct motor pathways: the corticospinal and the corticobulbar tracts.
The corticospinal tract is responsible for the voluntary movement of the limbs and trunk. It originates in the cerebral cortex of the brain and descends through the cerebrum's internal capsule and...
The corticospinal tract is responsible for the voluntary movement of the limbs and trunk. It originates in the cerebral cortex of the brain and descends through the cerebrum's internal capsule and...
4.7K
01:24Parkinson Disease ll: Pathophysiology
20
Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...
20
01:15Parkinson's Disease: Overview
2.2K
Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is...
2.2K