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Updated: May 29, 2026
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Single Synapse Indicators of Glutamate Release and Uptake in Acute Brain Slices from Normal and Huntington Mice
Published on: March 11, 2020
Pathophysiology of Huntington's disease: time-dependent alterations in synaptic and receptor function.
L A Raymond1, V M André, C Cepeda
1Department of Psychiatry and Brain Research Centre, University of British Columbia, Vancouver, Canada.
Neuroscience
|September 13, 2011
Summary
Huntington's disease (HD) involves CAG repeat expansions, leading to progressive neurological decline. Genetic mouse models reveal region-specific and time-dependent synaptic and receptor alterations, crucial for understanding disease progression and developing targeted treatments.
Area of Science:
- Neuroscience
- Genetics
- Neuropathology
Background:
- Huntington's disease (HD) is a fatal neurodegenerative disorder caused by CAG repeat expansion in the Huntington gene.
- Genetic animal models, particularly transgenic mice, are vital for studying HD's complex pathophysiological mechanisms.
- Classic neurotoxin models have limitations in elucidating progressive alterations seen in HD.
Purpose of the Study:
- To review synaptic and receptor alterations in medium-spiny neurons (MSNs) and cortical pyramidal neurons in genetic HD mouse models.
- To elucidate the region-specific and time-dependent nature of these alterations during disease progression.
- To highlight the role of excitotoxicity and glutamate dysregulation in HD pathogenesis.
Main Methods:
- Review of studies utilizing transgenic HD mouse models.
- Analysis of synaptic and receptor changes in striatal and cortical neurons.
- Examination of alterations related to glutamate release and N-methyl-D-aspartate receptors (NMDARs).
Main Results:
- Synaptic dysfunction in HD is region-specific and time-dependent, with early dysregulation of glutamate release in the striatum.
- Progressive disconnection between the cortex and striatum occurs, with early involvement of the direct striatal pathway.
- Early NMDAR dysfunction, particularly involving GluN2B subunits, enhances extrasynaptic receptor sensitivity.
Conclusions:
- Huntington's disease involves complex, bidirectional synaptic and receptor alterations.
- Treatment strategies for HD must consider the stage of disease progression and regional differences.
- Understanding these early synaptic and receptor dysfunctions is key to developing effective HD therapies.
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