scholarly journals MeCP2 deletion impaired layer 2/3-dominant dynamic reorganization of cortical circuit during motor skill learning

2019 ◽  
Author(s):  
Yuanlei Yue ◽  
Pan Xu ◽  
Zhichao Liu ◽  
Zekai Chen ◽  
Juntao Su ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Rett Syndrome ◽  
Motor Skill ◽  
Procedural Learning ◽  
Skill Learning ◽  
Motor Skill Learning ◽  
Layer 2 ◽  
Cortical Circuit ◽  
Circuit Reorganization

AbstractMotor cortex displays remarkable plasticity during motor learning. However, it remains largely unknown how the highly dynamic motor cortical circuit reorganizes during reward-independent procedural learning at the populational level. Machine learning-based analysis of the neuronal events recorded with in vivo two-photon calcium imaging revealed procedural learning-induced circuit reorganization in superficial but not deep layers of the motor cortex while mice learned to run on a speed-controlled treadmill. Mice lacking Methyl-CpG-binding protein (MeCP2), an animal model for Rett Syndrome, exhibited impaired both procedural learning and dynamic circuit reorganization in layer 2/3, but not layer 5a. These results identify potential circuit mechanisms underlying motor skill learning disability caused by MeCP2 deletion and provide insight in developing therapies for Rett syndrome.

scholarly journals Motor-Skill Learning Is Dependent on Astrocytic Activity

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Ragunathan Padmashri ◽  
Anand Suresh ◽  
Michael D. Boska ◽  
Anna Dunaevsky
Keyword(s):  
Motor Skill ◽  
Primary Motor Cortex ◽  
Skill Training ◽  
Long Term Potentiation ◽  
Skill Learning ◽  
Metabolic Inhibitor ◽  
Motor Skill Learning ◽  
Reaching Task ◽  
Learning Impairment

Motor-skill learning induces changes in synaptic structure and function in the primary motor cortex through the involvement of a long-term potentiation- (LTP-) like mechanism. Although there is evidence that calcium-dependent release of gliotransmitters by astrocytes plays an important role in synaptic transmission and plasticity, the role of astrocytes in motor-skill learning is not known. To test the hypothesis that astrocytic activity is necessary for motor-skill learning, we perturbed astrocytic function using pharmacological and genetic approaches. We find that perturbation of astrocytes either by selectively attenuating IP3R2 mediated astrocyte Ca2+signaling or using an astrocyte specific metabolic inhibitor fluorocitrate (FC) results in impaired motor-skill learning of a forelimb reaching-task in mice. Moreover, the learning impairment caused by blocking astrocytic activity using FC was rescued by administration of the gliotransmitter D-serine. The learning impairments are likely caused by impaired LTP as FC blocked LTP in slices and prevented motor-skill training-induced increases in synaptic AMPA-type glutamate receptorin vivo. These results support the conclusion that normal astrocytic Ca2+signaling during a reaching task is necessary for motor-skill learning.

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 Somatosensory changes associated with motor skill learning

2020 ◽  
Vol 123 (3) ◽  
pp. 1052-1062 ◽  
Author(s):  
Jasmine L. Mirdamadi ◽  
Hannah J. Block
Keyword(s):  
Motor Cortex ◽  
Motor Skill ◽  
Motor Adaptation ◽  
Short Latency ◽  
Skill Learning ◽  
Motor Skill Learning ◽  
Short Latency Afferent Inhibition ◽  
Afferent Inhibition ◽  
Speed Accuracy ◽  
Somatosensory Function

Trial-and-error motor adaptation has been linked to somatosensory plasticity and shifts in proprioception (limb position sense). The role of sensory processing in motor skill learning is less understood. Unlike adaptation, skill learning involves the acquisition of new movement patterns in the absence of perturbation, with performance limited by the speed-accuracy trade-off. We investigated somatosensory changes during motor skill learning at the behavioral and neurophysiological levels. Twenty-eight healthy young adults practiced a maze-tracing task, guiding a robotic manipulandum through an irregular two-dimensional track featuring several abrupt turns. Practice occurred on days 1 and 2. Skill was assessed before practice on day 1 and again on day 3, with learning indicated by a shift in the speed-accuracy function between these assessments. Proprioceptive function was quantified with a passive two-alternative forced-choice task. In a subset of 15 participants, we measured short-latency afferent inhibition (SAI) to index somatosensory projections to motor cortex. We found that motor practice enhanced the speed-accuracy skill function ( F4,108 = 32.15, P < 0.001) and was associated with improved proprioceptive sensitivity at retention ( t22 = 24.75, P = 0.0031). Furthermore, SAI increased after training ( F1,14 = 5.41, P = 0.036). Interestingly, individuals with larger increases in SAI, reflecting enhanced somatosensory afference to motor cortex, demonstrated larger improvements in motor skill learning. These findings suggest that SAI may be an important functional mechanism for some aspect of motor skill learning. Further research is needed to test what parameters (task complexity, practice time, etc.) are specifically linked to somatosensory function. NEW & NOTEWORTHY Somatosensory processing has been implicated in motor adaptation, where performance recovers from a perturbation such as a force field. We investigated somatosensory function during motor skill learning, where a new motor pattern is acquired in the absence of perturbation. After skill practice, we found changes in proprioception and short-latency afferent inhibition (SAI), signifying somatosensory change at both the behavioral and neurophysiological levels. SAI may be an important functional mechanism by which individuals learn motor skills.

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