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Reach task-associated excitatory overdrive of motor cortical neurons following infusion with ALS-CSF

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

Converging evidence from transgenic animal models of amyotrophic lateral sclerosis (ALS) and human studies suggest alterations in excitability of the motor neurons in ALS. Specifically, in studies on human subjects with ALS the motor cortex was reported to be hyperexcitable. The present study was designed to test the hypothesis that infusion of cerebrospinal fluid from patients with sporadic ALS (ALS-CSF) into the rat brain ventricle can induce hyperexcitability and structural changes in the motor cortex leading to motor dysfunction. A robust model of sporadic ALS was developed experimentally by infusing ALS-CSF into the rat ventricle. The effects of ALS-CSF at the single neuron level were examined by recording extracellular single unit activity from the motor cortex while rats were performing a reach to grasp task. We observed an increase in the firing rate of the neurons of the motor cortex in rats infused with ALS-CSF compared to control groups. This was associated with impairment in a specific component of reach with alterations in the morphological characteristics of the motor cortex. It is likely that the increased cortical excitability observed in the present study could be the result of changes in the intrinsic properties of motor cortical neurons, a dysfunctional inhibitory mechanism and/or an underlying structural change culminating in a behavioral deficit.

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Abbreviations

ALS:

Amyotrophic lateral sclerosis

ALS-CSF:

Cerebrospinal fluid from patients with sporadic ALS

LFPs:

Local field potentials

Fps:

Frames per second

MI:

Primary motor cortex

MAP:

Multichannel acquisition processor

Non-ALS-CSF:

Non-degenerative neurological disorders

PETHs:

Peri-event time histograms

MΔFR:

Mean delta firing rate

I FRC :

Index of firing rate change

PEFR:

Peri-event firing rate

ΔPEFR:

Differential PEFR

Vref:

Volume of rostral forelimb region of MI

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Authors and Affiliations

  1. Department of Neurophysiology, National Institute of Mental Health and Neurosciences (NIMHANS), Post Box No: 2900, Hosur Road, Bangalore, 560 029, Karnataka, India

    R. Sankaranarayani, T. R. Laxmi & T. R. Raju

  2. Department of Neurology, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore, 560 029, Karnataka, India

    A. Nalini

  3. Electrical Communication Engineering, Indian Institute of Science, Bangalore, 560 012, Karnataka, India

    Mohan Raghavan

Authors
  1. R. Sankaranarayani
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  2. Mohan Raghavan
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  3. A. Nalini
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  4. T. R. Laxmi
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  5. T. R. Raju
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Correspondence to T. R. Raju.

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Sankaranarayani, R., Raghavan, M., Nalini, A. et al. Reach task-associated excitatory overdrive of motor cortical neurons following infusion with ALS-CSF. J Neural Transm 121, 49–58 (2014). https://doi.org/10.1007/s00702-013-1071-4

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  • DOI: https://doi.org/10.1007/s00702-013-1071-4

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