scholarly journals Knockdown of astrocytic monocarboxylate transporter 4 (MCT4) in the motor cortex leads to loss of dendritic spines and a deficit in motor learning

2021 ◽  
Author(s):  
Adam J. Lundquist ◽  
George N. Llewellyn ◽  
Susan H. Kishi ◽  
Nicolaus A. Jakowec ◽  
Paula M. Cannon ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Motor Learning ◽  
Neuronal Activity ◽  
Near Infrared ◽  
Primary Motor Cortex ◽  
Surrogate Marker ◽  
Dorsal Striatum ◽  
Monocarboxylate Transporter ◽  
Spine Density ◽  
Lactate Shuttle

Monocarboxylate transporters (MCTs) shuttle molecules, including L-lactate, involved in metabolism and cell signaling of the central nervous system. Astrocyte-specific MCT4 is a key component of the astrocyte-neuron lactate shuttle (ANLS) and is important for neuroplasticity and learning of the hippocampus. However, the importance of astrocyte-specific MCT4 in neuroplasticity of the M1 primary motor cortex remains unknown. In this study, we investigated astrocyte-specific MCT4 in motor learning and neuroplasticity of the M1 primary motor cortex using a cell-type specific shRNA knockdown of MCT4. Knockdown of astrocyte-specific MCT4 resulted in impaired motor performance and learning on the accelerating rotarod. In addition, MCT4 knockdown was associated with a reduction of neuronal dendritic spine density and spine width and decreased protein expression of PSD95 and Arc. Using near-infrared-conjugated 2-deoxyglucose uptake as a surrogate marker for neuronal activity, MCT4 knockdown was also associated with decreased neuronal activity in the M1 primary motor cortex and associated motor regions including the dorsal striatum and ventral thalamus. Our study supports a potential role for astrocyte-specific MCT4 and the ANLS in the neuroplasticity of the M1 primary motor cortex. Targeting MCT4 may serve to enhance neuroplasticity and motor repair in several neurological disorders, including Parkinson's disease and stroke.

scholarly journals Enhancing motor learning by increasing stability of newly formed dendritic spines in motor cortex

2021 ◽  
Author(s):  
Eddy Albarran ◽  
Aram Raissi ◽  
Omar Jáidar ◽  
Carla J. Shatz ◽  
Jun B. Ding
Keyword(s):  
Motor Cortex ◽  
Motor Learning ◽  
Motor Skills ◽  
Motor Performance ◽  
Primary Motor Cortex ◽  
Pyramidal Neurons ◽  
Spine Density ◽  
Immunoglobulin Receptor ◽  
Reaching Task ◽  
Spine Dynamics

SUMMARYDendritic spine dynamics of Layer 5 Pyramidal neurons (L5PNs) are thought to be physical substrates for motor learning and memory of motor skills and altered spine dynamics are frequently correlated with poor motor performance. Here we describe an exception to this rule by studying mice lacking Paired immunoglobulin receptor B (PirB−/−). Using chronic two-photon imaging of primary motor cortex (M1) of PirB−/−;Thy1-YFP-H mice, we found a significant increase in the survival of spines on apical dendritic tufts of L5PNs, as well as increased spine formation rates and spine density. Surprisingly and contrary to expectations, adult PirB−/− mice learn a skilled reaching task more rapidly compared to wild type (WT) littermate controls. Conditional excision of PirB from forebrain pyramidal neurons in adult mice replicated these results. Furthermore, chronic imaging of L5PN dendrites throughout the learning period revealed that the stabilization of learning-induced newly formed spines is significantly elevated in PirB−/− mice. The degree of survival of newly formed spines in M1 yielded the strongest correlation with task performance, suggesting that this increased spine stability is advantageous and can translate into enhanced acquisition and maintenance of motor skills. Notably, inhibiting PirB function acutely in M1 of adult WT mice throughout training increases the survival of spines formed during early training and enhances motor learning. These results suggest that increasing the stability of newly formed spines is sufficient to improve long-lasting learning and motor performance and demonstrate that there are limits on motor learning that can be lifted by manipulating PirB, even in adulthood.

Transcranial static magnetic stimulation over the primary motor cortex alters sequential implicit motor learning

2019 ◽  
Vol 696 ◽  
pp. 33-37 ◽  
Author(s):  
Ippei Nojima ◽  
Tatsunori Watanabe ◽  
Tomoya Gyoda ◽  
Hisato Sugata ◽  
Takashi Ikeda ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Motor Learning ◽  
Magnetic Stimulation ◽  
Primary Motor Cortex ◽  
Implicit Motor Learning ◽  
Implicit Motor

scholarly journals A Concept for Extending the Applicability of Constraint-Induced Movement Therapy through Motor Cortex Activity Feedback Using a Neural Prosthesis

2007 ◽  
Vol 2007 ◽  
pp. 1-9 ◽  
Author(s):  
Tomas E. Ward ◽  
Christopher J. Soraghan ◽  
Fiachra Matthews ◽  
Charles Markham
Keyword(s):  
Infrared Spectroscopy ◽  
Motor Cortex ◽  
Healthy Subjects ◽  
Near Infrared ◽  
Primary Motor Cortex ◽  
Movement Therapy ◽  
Robotic Arm ◽  
Current Status ◽  
Constraint Induced Movement Therapy ◽  
Basic Technology

This paper describes a concept for the extension of constraint-induced movement therapy (CIMT) through the use of feedback of primary motor cortex activity. CIMT requires residual movement to act as a source of feedback to the patient, thus preventing its application to those with no perceptible movement. It is proposed in this paper that it is possible to provide feedback of the motor cortex effort to the patient by measurement with near infrared spectroscopy (NIRS). Significant changes in such effort may be used to drive rehabilitative robotic actuators, for example. This may provide a possible avenue for extending CIMT to patients hitherto excluded as a result of severity of condition. In support of such a paradigm, this paper details the current status of CIMT and related attempts to extend rehabilitation therapy through the application of technology. An introduction to the relevant haemodynamics is given including a description of the basic technology behind a suitable NIRS system. An illustration of the proposed therapy is described using a simple NIRS system driving a robotic arm during simple upper-limb unilateral isometric contraction exercises with healthy subjects.

scholarly journals Protective role of mirtazapine in adult female Mecp2+/− mice and patients with Rett syndrome

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Javier Flores Gutiérrez ◽  
Claudio De Felice ◽  
Giulia Natali ◽  
Silvia Leoncini ◽  
Cinzia Signorini ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Motor Learning ◽  
Disease Progression ◽  
Rett Syndrome ◽  
Adult Female ◽  
Primary Motor Cortex ◽  
Barrel Cortex ◽  
Motor Behavior ◽  
Clinical Severity ◽  
Long Term Treatment

Abstract Background Rett syndrome (RTT), an X-linked neurodevelopmental rare disease mainly caused by MECP2-gene mutations, is a prototypic intellectual disability disorder. Reversibility of RTT-like phenotypes in an adult mouse model lacking the Mecp2-gene has given hope of treating the disease at any age. However, adult RTT patients still urge for new treatments. Given the relationship between RTT and monoamine deficiency, we investigated mirtazapine (MTZ), a noradrenergic and specific-serotonergic antidepressant, as a potential treatment. Methods Adult heterozygous-Mecp2 (HET) female mice (6-months old) were treated for 30 days with 10 mg/kg MTZ and assessed for general health, motor skills, motor learning, and anxiety. Motor cortex, somatosensory cortex, and amygdala were analyzed for parvalbumin expression. Eighty RTT adult female patients harboring a pathogenic MECP2 mutation were randomly assigned to treatment to MTZ for insomnia and mood disorders (mean age = 23.1 ± 7.5 years, range = 16–47 years; mean MTZ-treatment duration = 1.64 ± 1.0 years, range = 0.08–5.0 years). Rett clinical severity scale (RCSS) and motor behavior assessment scale (MBAS) were retrospectively analyzed. Results In HET mice, MTZ preserved motor learning from deterioration and normalized parvalbumin levels in the primary motor cortex. Moreover, MTZ rescued the aberrant open-arm preference behavior observed in HET mice in the elevated plus-maze (EPM) and normalized parvalbumin expression in the barrel cortex. Since whisker clipping also abolished the EPM-related phenotype, we propose it is due to sensory hypersensitivity. In patients, MTZ slowed disease progression or induced significant improvements for 10/16 MBAS-items of the M1 social behavior area: 4/7 items of the M2 oro-facial/respiratory area and 8/14 items of the M3 motor/physical signs area. Conclusions This study provides the first evidence that long-term treatment of adult female heterozygous Mecp2tm1.1Bird mice and adult Rett patients with the antidepressant mirtazapine is well tolerated and that it protects from disease progression and improves motor, sensory, and behavioral symptoms.

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