Cortical Network Dynamics Is Altered in Mouse Models of Huntington’s Disease.

Cortical Network Dynamics Is Altered in Mouse Models of Huntington’s Disease.

Publication date: Nov 25, 2019

Huntington’s disease (HD) is a neurodegenerative disorder characterized by involuntary movements, cognitive deficits, and psychiatric disturbances. Although evidence indicates that projections from motor cortical areas play a key role in the development of dysfunctional striatal activity and motor phenotype, little is known about the changes in cortical microcircuits and their role in the development of the HD phenotype. Here we used two-photon laser-scanning microscopy to evaluate network dynamics of motor cortical neurons in layers II/III in behaving transgenic R6/2 and knock-in Q175+/- mice. Symptomatic R6/2 mice displayed increased motion manifested by a significantly greater number of motion epochs, whereas symptomatic Q175 mice displayed decreased motion. In both models, calcium transients in symptomatic mice displayed reduced amplitude, suggesting decreased bursting activity. Changes in frequency were genotype- and time-dependent; for R6/2 mice, the frequency was reduced during both motion and nonmotion, whereas in symptomatic Q175 mice, the reduction only occurred during nonmotion. In presymptomatic Q175 mice, frequency was increased during both behavioral states. Interneuronal correlation coefficients were generally decreased in both models, suggesting disrupted interneuronal communication in HD cerebral cortex. These results indicate similar and contrasting effects of the HD mutation on cortical ensemble activity depending on mouse model and disease stage.

Donzis, E.J., Estrada-S’anchez, A.M., Indersmitten, T., Oikonomou, K., Tran, C.H., Wang, C., Latifi, S., Golshani, P., Cepeda, C., and Levine. Cortical Network Dynamics Is Altered in Mouse Models of Huntington’s Disease. 06796. 2019 Cereb Cortex.

Concepts Keywords
Amplitude Imaging
Calcium Involuntary movements
Cerebral Cortex HD neurodegenerative disorder
Cognitive Cerebral cortex
Correlation Coefficients Medical terminology
Cortical Neuron
Frequency Laser
Genotype Genotype
Laser Scanning
Neurodegenerative Disorder


Type Source Name
disease MESH neurodegenerative disorder
disease MESH involuntary movements
disease MESH development
drug DRUGBANK Calcium


Original Article

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