scholarly journals Lack of mutant huntingtin in cortical efferents improves behavioral inflexibility and corticostriatal dynamics in Huntington’s disease mice

2019 ◽  
Vol 122 (6) ◽  
pp. 2621-2629
Author(s):  
Ana María Estrada-Sánchez ◽  
Courtney L. Blake ◽  
Scott J. Barton ◽  
Andrew G. Howe ◽  
George V. Rebec
Keyword(s):  
Motor Cortex ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Local Field ◽  
Local Field Potential ◽  
Primary Motor Cortex ◽  
Field Potential ◽  
Full Length ◽  
Mutant Huntingtin ◽  
Local Field Potential Lfp

Abnormal communication between cerebral cortex and striatum plays a major role in the motor symptoms of Huntington’s disease (HD), a neurodegenerative disorder caused by a mutation of the huntingtin gene ( mHTT). Because cortex is the main driver of striatal processing, we recorded local field potential (LFP) activity simultaneously in primary motor cortex (M1) and dorsal striatum (DS) in BACHD mice, a full-length HD gene model, and in a conditional BACHD/Emx-1 Cre (BE) model in which mHTT is suppressed in cortical efferents, while mice freely explored a plus-shaped maze beginning at 20 wk of age. Relative to wild-type (WT) controls, BACHD mice were just as active across >40 wk of testing but became progressively less likely to turn into a perpendicular arm as they approached the choice point of the maze, a sign of HD motor inflexibility. BE mice, in contrast, turned as freely as WT throughout testing. Although BE mice did not exactly match WT in LFP activity, the reduction in alpha (8–13 Hz), beta (13–30 Hz), and low-gamma (30–50 Hz) power that occurred in M1 of turning-impaired BACHD mice was reversed. No reversal occurred in DS. In fact, BE mice showed further reductions in DS theta (4–8 Hz), beta, and low-gamma power relative to the BACHD model. Coherence analysis indicated a dysregulation of corticostriatal information flow in both BACHD and BE mice. Collectively, our results suggest that mHTT in cortical outputs drives the dysregulation of select cortical frequencies that accompany the loss of behavioral flexibility in HD. NEW & NOTEWORTHY BACHD mice, a full-length genetic model of Huntington’s disease (HD), express aberrant local field potential (LFP) activity in primary motor cortex (M1) along with decreased probability of turning into a perpendicular arm of a plus-shaped maze, a motor inflexibility phenotype. Suppression of the mutant huntingtin gene in cortical output neurons prevents decline in turning and improves alpha, beta, and low-gamma activity in M1. Our results implicate cortical networks in the search for therapeutic strategies to alleviate HD motor signs.

scholarly journals Chronic Stability of Single-Channel Neurophysiological Correlates of Gross and Fine Reaching Movements in the Rat

2019 ◽  
Author(s):  
David T. Bundy ◽  
David J Guggenmos ◽  
Maxwell D Murphy ◽  
Randolph J. Nudo
Keyword(s):  
Motor Cortex ◽  
Local Field ◽  
Neural Activity ◽  
Local Field Potential ◽  
Primary Motor Cortex ◽  
Spectral Power ◽  
Premotor Cortex ◽  
Field Potential ◽  
Motor Recovery ◽  
Reaching Movements

AbstractFollowing injury to motor cortex, reorganization occurs throughout spared brain regions and is thought to underlie motor recovery. Unfortunately, the standard neurophysiological and neuroanatomical measures of post-lesion plasticity are only indirectly related to observed changes in motor execution. While substantial task-related neural activity has been observed during motor tasks in rodent primary motor cortex and premotor cortex, the long-term stability of these responses in healthy rats is uncertain, limiting the interpretability of longitudinal changes in the specific patterns of neural activity during motor recovery following injury. This study examined the stability of task-related neural activity associated with execution of reaching movements in healthy rodents. Rats were trained to perform a novel reaching task combining a ‘gross’ lever press and a ‘fine’ pellet retrieval. In each animal, two chronic microelectrode arrays were implanted in motor cortex spanning the caudal forelimb area (rodent primary motor cortex) and the rostral forelimb area (rodent premotor cortex). We recorded multiunit spiking and local field potential activity from 10 days to 7-10 weeks post-implantation to characterize the patterns of neural activity observed during each task component and analyzed the consistency of channel-specific task-related neural activity. Task-related changes in neural activity were observed on the majority of channels. While the task-related changes in multi-unit spiking and local field potential spectral power were consistent over several weeks, spectral power changes were more stable, despite the trade-off of decreased spatial and temporal resolution. These results show that rodent primary and premotor cortex are both involved in reaching movements with stable patterns of task-related activity across time, establishing the relevance of the rodent for future studies designed to examine changes in task-related neural activity during recovery from focal cortical lesions.

Local field potential oscillations of the globus pallidus in Huntington's disease

2011 ◽  
Vol 26 (14) ◽  
pp. 2577-2578 ◽  
Author(s):  
Stefan Jun Groiss ◽  
Saskia Elben ◽  
Christiane Reck ◽  
Jürgen Voges ◽  
Lars Wojtecki ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Globus Pallidus ◽  
Local Field ◽  
Local Field Potential ◽  
Field Potential ◽  
Potential Oscillations

scholarly journals Identification of Full-Length Wild-Type and Mutant Huntingtin Interacting Proteins by Crosslinking Immunoprecipitation in Mice Brain Cortex

2021 ◽  
pp. 1-13
Author(s):  
Karen A. Sap ◽  
Arzu Tugce Guler ◽  
Aleksandra Bury ◽  
Dick Dekkers ◽  
Jeroen A.A. Demmers ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Brain Cortex ◽  
Full Length ◽  
Biological Processes ◽  
Interacting Proteins ◽  
Mutant Huntingtin ◽  
Wild Type ◽  
Mutant Huntingtin Protein ◽  
Mice Brain

Background: Huntington’s disease is a neurodegenerative disorder caused by a CAG expansion in the huntingtin gene, resulting in a polyglutamine expansion in the ubiquitously expressed mutant huntingtin protein. Objective: Here we set out to identify proteins interacting with the full-length wild-type and mutant huntingtin protein in the mice cortex brain region to understand affected biological processes in Huntington’s disease pathology. Methods: Full-length huntingtin with 20 and 140 polyQ repeats were formaldehyde-crosslinked and isolated via their N-terminal Flag-tag from 2-month-old mice brain cortex. Interacting proteins were identified and quantified by label-free liquid chromatography-mass spectrometry (LC-MS/MS). Results: We identified 30 interactors specific for wild-type huntingtin, 14 interactors specific for mutant huntingtin and 14 shared interactors that interacted with both wild-type and mutant huntingtin, including known interactors such as F8a1/Hap40. Syt1, Ykt6, and Snap47, involved in vesicle transport and exocytosis, were among the proteins that interacted specifically with wild-type huntingtin. Various other proteins involved in energy metabolism and mitochondria were also found to associate predominantly with wild-type huntingtin, whereas mutant huntingtin interacted with proteins involved in translation including Mapk3, Eif3h and Eef1a2. Conclusion: Here we identified both shared and specific interactors of wild-type and mutant huntingtin, which are involved in different biological processes including exocytosis, vesicle transport, translation and metabolism. These findings contribute to the understanding of the roles that wild-type and mutant huntingtin play in a variety of cellular processes both in healthy conditions and Huntington’s disease pathology.

scholarly journals Cortical circuit alterations precede disease onset in Huntington’s disease mice

2018 ◽  
Author(s):  
Johanna Neuner ◽  
Elena Katharina Schulz-Trieglaff ◽  
Sara Gutiérrez-Ángel ◽  
Fabian Hosp ◽  
Matthias Mann ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Primary Motor Cortex ◽  
Disease Onset ◽  
Single Neurons ◽  
Two Photon ◽  
Layer 2 ◽  
Cortical Circuit

AbstractHuntington’s disease (HD) is a devastating hereditary movement disorder, characterized by degeneration of neurons in the striatum and cortex. Studies in human patients and mouse HD models suggest that disturbances of neuronal function in the neocortex play an important role in the disease onset and progression. However, the precise nature and time course of cortical alterations in HD have remained elusive. Here, we use chronicin vivotwo-photon calcium imaging to monitor the activity of single neurons in layer 2/3 of the primary motor cortex in awake, behaving R6/2 transgenic HD mice and wildtype littermates. R6/2 mice show age-dependent changes in neuronal activity with a clear increase in activity at the age of 8.5 weeks, preceding the onset of motor and neurological symptoms. Furthermore, quantitative proteomics demonstrate a pronounced downregulation of synaptic proteins in the cortex, and histological analyses in R6/2 mice and HD patient samples reveal reduced inputs from parvalbumin-positive interneurons onto layer 2/3 pyramidal cells. Thus, our study provides a time-resolved description as well as mechanistic details of cortical circuit dysfunction in HD.Significance statementFuntional alterations in the cortex are believed to play an important role in the pathogenesis of Huntington’s disease (HD). However, studies monitoring cortical activity in HD modelsin vivoat a single-cell resultion are still lacking. We have used chronic two-photon imaging to investigate changes in the activity of single neurons in the primary motor cortex of awake presymptomatic HD mice. We show that neuronal activity increases before the mice develop disease symptoms. Our histological analyses in mice and in human HD autopsy cases furthermore demonstrate a loss inhibitory synaptic terminals from parvalbimun-positive interneurons, revealing a potential mechanism of cortical circuit impairment in HD.

scholarly journals Learning Task-Related Activities From Independent Local-Field-Potential Components Across Motor Cortex Layers

2018 ◽  
Vol 12 ◽  
Author(s):  
Gonzalo Martín-Vázquez ◽  
Toshitake Asabuki ◽  
Yoshikazu Isomura ◽  
Tomoki Fukai
Keyword(s):  
Motor Cortex ◽  
Local Field ◽  
Local Field Potential ◽  
Field Potential ◽  
Learning Task

scholarly journals Comparison of tuning properties of gamma and high-gamma power in local field potential (LFP) versus electrocorticogram (ECoG) in visual cortex

2019 ◽  
Author(s):  
Agrita Dubey ◽  
Supratim Ray
Keyword(s):  
Visual Cortex ◽  
Local Field ◽  
Local Field Potential ◽  
Field Potential ◽  
Gamma Oscillations ◽  
Orientation Contrast ◽  
High Gamma ◽  
Gamma Power ◽  
Electrocorticogram Ecog ◽  
Local Field Potential Lfp

AbstractElectrocorticogram (ECoG), obtained from macroelectrodes placed on the cortex, is typically used in drug-resistant epilepsy patients, and is increasingly being used to study cognition in humans. These studies often use power in gamma (30-70 Hz) or high-gamma (>80 Hz) ranges to make inferences about neural processing. However, while the stimulus tuning properties of gamma/high-gamma power have been well characterized in local field potential (LFP; obtained from microelectrodes), analogous characterization has not been done for ECoG. Using a hybrid array containing both micro and ECoG electrodes implanted in the primary visual cortex of two female macaques, we compared the stimulus tuning preferences of gamma/high-gamma power in LFP versus ECoG and found them to be surprisingly similar. High-gamma power, thought to index the average firing rate around the electrode, was highest for the smallest stimulus (0.3° radius), and decreased with increasing size in both LFP and ECoG, suggesting local origins of both signals. Further, gamma oscillations were similarly tuned in LFP and ECoG to stimulus orientation, contrast and spatial frequency. This tuning was significantly weaker in electroencephalogram (EEG), suggesting that ECoG is more like LFP than EEG. Overall, our results validate the use of ECoG in clinical and basic cognitive research.

scholarly journals Novel Porous Brain Electrodes for Augmented Local Field Potential Signal Detection

Materials ◽  
2019 ◽  
Vol 12 (3) ◽  
pp. 542 ◽  
Author(s):  
Sung Lee ◽  
Kyeong-Seok Lee ◽  
Saurav Sorcar ◽  
Abdul Razzaq ◽  
Maan-Gee Lee ◽  
...  
Keyword(s):  
Local Field ◽  
Local Field Potential ◽  
Brain Activity ◽  
Field Potential ◽  
Porous Electrodes ◽  
Surface Topology ◽  
Neural Electrode ◽  
Flow Of Information ◽  
Potential Signal ◽  
Local Field Potential Lfp

Intracerebral local field potential (LFP) measurements are commonly used to monitor brain activity, providing insight into the flow of information across neural networks. Herein we describe synthesis and application of a neural electrode possessing a nano/micro-scale porous surface topology for improved LFP measurement. Compared with conventional brain electrodes, the porous electrodes demonstrate higher measured amplitudes with lower noise levels.

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