Corticostriatal synaptic plasticity alterations in the R6/1 transgenic mouse model of Huntington’s disease.

Corticostriatal synaptic plasticity alterations in the R6/1 transgenic mouse model of Huntington’s disease.

Publication date: Sep 09, 2019

Huntington’s disease (HD) is a genetic neurodegenerative condition characterized by abnormal dopamine (DA)-glutamate interactions, severe alterations in motor control, and reduced behavioral flexibility. Experimental models of disease show that during symptomatic phases, HD shares with other hyperkinetic disorders the loss of synaptic depotentiation in the striatal spiny projection neurons (SPNs). Here we test the hypothesis that corticostriatal long-term depression (LTD), a well-conserved synaptic scaling down response to environmental stimuli, is also altered in symptomatic male R6/1 mice, a HD model with gradual development of symptoms. In vitro patch-clamp and intracellular recordings of corticostriatal slices from R6/1 mice confirm that, similar to other models characterized by hyperkinesia and striatal DA D1 receptor pathway dysregulation, once long-term potentiation (LTP) is induced, synaptic depotentiation is lost. Our new observations show that activity-dependent LTD was abolished in SPNs of mutant mice. In an experimental condition in which N-methyl-d-aspartate (NMDA) receptors are normally not recruited, in vitro bath application of DA revealed an abnormal response of D1 receptors that caused a shift in synaptic plasticity direction resulting in an NMDA-dependent LTP. Our results demonstrate that corticostriatal LTD is lost in R6/1 mouse model and confirm the role of aberrant DA-glutamate interactions in the alterations of synaptic scaling down associated with HD symptoms.

, Ghiglieri, Campanelli, F., Marino, G., Natale, G., Picconi, B., and Calabresi, P. Corticostriatal synaptic plasticity alterations in the R6/1 transgenic mouse model of Huntington’s disease. 06672. 2019 J Neurosci Res.

Concepts Keywords
Aspartate Synaptic plasticity
Corticostriatal Long-term depression
DA Synaptic scaling
Dopamine Long-term potentiation
Genetic Neural circuits
Glutamate Neurology
Huntington Memory
Intracellular Neurophysiology
Long Term Depression Neuroplasticity
Long Term Potentiation Neuroscience
LTP Branches of biology
Methyl Hyperkinesia
Mice
Motor Control
Mutant
Neurodegenerative Condition
Neurons
NMDA
Patch Clamp
Receptor
Receptors
Striatal
Synaptic
Synaptic Plasticity
Transgenic

Semantics

Type Source Name
drug DRUGBANK Ketamine
pathway BSID Long-term potentiation
disease MESH hyperkinesia
disease MESH development
pathway BSID Long-term depression
drug DRUGBANK Dopamine

Original Article

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