Measuring Spinal Presynaptic Inhibition in Mice By Dorsal Root Potential Recording &lt;em&gt;In Vivo&lt;/em&gt;

Grünewald, Benedikt; Geis, Christian

doi:10.3791/51473

Cited by 5 publications

(4 citation statements)

References 24 publications

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“…Pre-synaptic inhibition is an important factor in regulating the monosynaptic reflexes (Eccles et al 1963;Levy, 1977;Hackman et al 1997). In vivo measurements of DRP have been used to estimate spinal presynaptic inhibition (Grunewald & Geis, 2014). In the present study, we found electrophysiological evidence that presynaptic inhibition was increased by a-tsDCS, in agreement with the findings by Kaczmarek et al (2017), and by bumetanide (NKCC1 blocker) ( Fig.…”

Section: Discussionsupporting

confidence: 90%

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Repeated anodal trans‐spinal direct current stimulation results in long‐term reduction of spasticity in mice with spinal cord injury

Mekhael

Begum

Samaddar

et al. 2019

The Journal of Physiology

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Key points Spasticity is a disorder of muscle tone that is associated with lesions of the motor system. This condition involves an overactive spinal reflex loop that resists the passive lengthening of muscles. Previously, we established that application of anodal trans‐spinal direct current stimulation (a‐tsDCS) for short periods of time to anaesthetized mice sustaining a spinal cord injury leads to an instantaneous reduction of spasticity. However, the long‐term effects of repeated a‐tsDCS and its mechanism of action remained unknown. In the present study, a‐tsDCS was performed for 7 days and this was found to cause long‐term reduction in spasticity, increased rate‐dependent depression in spinal reflexes, and improved ground and skill locomotion. Pharmacological, molecular and cellular evidence further suggest that a novel mechanism involving Na‐K‐Cl cotransporter isoform 1 mediates the observed long‐term effects of repeated a‐tsDCS. Abstract Spasticity can cause pain, fatigue and sleep disturbances; restrict daily activities such as walking, sitting and bathing; and complicate rehabilitation efforts. Thus, spasticity negatively influences an individual's quality of life and novel therapeutic interventions are needed. We previously demonstrated in anaesthetized mice that a short period of trans‐spinal subthreshold direct current stimulation (tsDCS) reduces spasticity. In the present study, the long‐term effects of repeated tsDCS to attenuate abnormal muscle tone in awake female mice with spinal cord injuries were investigated. A motorized system was used to test velocity‐dependent ankle resistance and associated electromyographical activity. Analysis of ground and skill locomotion was also performed, with electrophysiological, molecular and cellular studies being conducted to reveal a potential underlying mechanism of action. A 4 week reduction in spasticity was associated with an increase in rate‐dependent depression of spinal reflexes, and ground and skill locomotion were improved following 7 days of anodal‐tsDCS (a‐tsDCS). Secondary molecular, cellular and pharmacological experiments further demonstrated that the expression of K‐Cl co‐transporter isoform 2 (KCC2) was not changed in animals with spasticity. However, Na‐K‐Cl cotransporter isoform 1 (NKCC1) was significantly up‐regulated in mice that exhibited spasticity. When mice were treated with a‐tsDCS, down regulation of NKCC1 was detected, and this level did not significantly differ from that in the non‐injured control mice. Thus, long lasting reduction of spasticity by a‐tsDCS via downregulation of NKCC1 may constitute a novel therapy for spasticity following spinal cord injury.

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Section: Discussionsupporting

confidence: 90%

“…). In vivo measurements of DRP have been used to estimate spinal presynaptic inhibition (Grunewald & Geis, ). In the present study, we found electrophysiological evidence that presynaptic inhibition was increased by a‐tsDCS, in agreement with the findings by Kaczmarek et al .…”

Section: Discussionmentioning

confidence: 99%

Repeated anodal trans‐spinal direct current stimulation results in long‐term reduction of spasticity in mice with spinal cord injury

Mekhael

Begum

Samaddar

et al. 2019

The Journal of Physiology

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“…In vivo recordings of DRP in mice were performed as described ( Grünewald and Geis, 2014 ). Briefly, animals were deeply anesthetized and a dorsal laminectomy was performed from lumbar to thoracic levels to expose the spinal cord and dorsal roots and the dura mater was carefully removed.…”

Section: Methodsmentioning

confidence: 99%

Defective synaptic transmission causes disease signs in a mouse model of juvenile neuronal ceroid lipofuscinosis

Grünewald

Lange

Werner

et al. 2017

eLife

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Juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease) caused by mutations in the CLN3 gene is the most prevalent inherited neurodegenerative disease in childhood resulting in widespread central nervous system dysfunction and premature death. The consequences of CLN3 mutation on the progression of the disease, on neuronal transmission, and on central nervous network dysfunction are poorly understood. We used Cln3 knockout (Cln3Δex1-6) mice and found increased anxiety-related behavior and impaired aversive learning as well as markedly affected motor function including disordered coordination. Patch-clamp and loose-patch recordings revealed severely affected inhibitory and excitatory synaptic transmission in the amygdala, hippocampus, and cerebellar networks. Changes in presynaptic release properties may result from dysfunction of CLN3 protein. Furthermore, loss of calbindin, neuropeptide Y, parvalbumin, and GAD65-positive interneurons in central networks collectively support the hypothesis that degeneration of GABAergic interneurons may be the cause of supraspinal GABAergic disinhibition.

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“…А g , А d , сгенерирован полисинаптическими нейронами V-VII слоев. Медленная позитивная (Р) волна (направ-лена вниз относительно базиса) генерируется мелки-ми нейронами желатинозной субстанции СМ (II-III слоев) и отражает временную деполяризацию пер-вичных афферентов, приводящую к угнетению аффе-рентной эффективности [9,10].…”

Section: распределениеunclassified

The distribution of spinal evoked potentials across dorsal surface in conditions of dorsal roots transection

Shugurov¹

2017

ScienceRise: Biological Science

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Measuring Spinal Presynaptic Inhibition in Mice By Dorsal Root Potential Recording <em>In Vivo</em>

Cited by 5 publications

References 24 publications

Repeated anodal trans‐spinal direct current stimulation results in long‐term reduction of spasticity in mice with spinal cord injury

Repeated anodal trans‐spinal direct current stimulation results in long‐term reduction of spasticity in mice with spinal cord injury

Defective synaptic transmission causes disease signs in a mouse model of juvenile neuronal ceroid lipofuscinosis

The distribution of spinal evoked potentials across dorsal surface in conditions of dorsal roots transection

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