Name: rodent behavioral testing to assess functional deficits caused by microelectrode implantation in the rat motor cortex
Uploaded: 2018-08-18T12:30:00
Description: Watch this Scientific Journal Video about Rodent Behavioral Testing to Assess Functional Deficits Caused by Microelectrode Implantation in the Rat Motor Cortex at JoVE.com

This study was supported in part by the Merit Review Award #B1495-R (Capadona) and the Presidential Early Career Award for Scientist and Engineers (PECASE, Capadona) from the United States (US) Department of Veterans Affairs Rehabilitation Research and Development Service. Additionally, this work was supported in part by the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program under Award No. W81XWH-15-1-0608. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. The authors would like to thank Dr. Hiroyuki Arakawa in the CWRU Rodent Behavior Core for his guidance in designing and testing rodent behavioral protocols. The authors would also like to thank James Drake and Kevin Talbot from the CWRU Department of Mechanical and Aerospace Engineering for their help in designing and manufacturing the rodent ladder test.

All procedures and animal care practices were approved by and performed in accordance with the Louis Stokes Cleveland Department of Veterans Affairs Medical Center Institutional Animal Care and Use Committees.
NOTE: To educate researchers on the decision about the use of a stab injury model as a control, it is recommended to review the work done by Potter et al.21.
1. Microelectrode Implantation Surgical Procedure
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The protocol outlined here has been used to effectively and reproducibly measure both fine and gross motor deficit in a model of rodent brain injury. Additionally, it allows for the correlation of fine motor behavior to histological outcomes following a microelectrode implantation in the motor cortex. The methods are easy to follow, inexpensive to set up, and can be modified to fit a researcher&#39;s individual needs. Further, the behavior testing does not cause great stress or pain to the animals; rather, the researcher...

Intracortical microelectrodes were originally used to map the circuitry of the brain, and have developed into a valuable tool to enable the detection of motor intentions which can be used to produce functional outputs1. Detected functional outputs can offer individuals suffering from spinal cord injuries, cerebral palsy, amyotrophic lateral sclerosis (ALS), or other movement-limiting conditions the control of a computer cursor2,3 or robotic arm4,5,6, or restore function to their own disabled limb7. Therefore, intracortical microelectrode technology has emerged as a promising and quickly growing field8.
Due to the successes seen in the field, clinical studies are underway to improve and better understand the possibilities of BMI technology5,9,10. By realizing the full potential of communication with neurons in the brain, the rehabilitation applications are perceived as limitless8. Although there is great optimism for the future of intracortical microelectrode technology, it is also well-known that microelectrodes eventually fail11, possibly due to an acute neuroinflammatory response following implantation. The implantation of a foreign material in the brain results in immediate damage to the surrounding tissue and leads to further damage caused by the neuroinflammatory response that varies depending on properties of the implant12. In addition, an implant&#160;in the brain can cause a microlesion effect: a reduction in glucose metabolism thought to be caused by acute edema and hemorrhage due to the device insertion13. Furthermore, the signal quality and the length of time that useful signals can be recorded are inconsistent, regardless of the animal model11,14,15,16. Several studies have demonstrated the connection between neuroinflammation and microelectrode performance17,18,19. Therefore, the consensus of the community is that the inflammatory response of the neural tissue that surrounds the microelectrodes, at least in part, compromises electrode reliability.
Many studies have examined local inflammation11,20,21,22 or explored methods to reduce the damage to the brain caused by insertion11,23,24,25, with a goal of improving the recording performance over time14,26. Additionally, we have recently shown that an iatrogenic injury caused by a microelectrode insertion in the motor cortex of rats causes an immediate and lasting fine motor deficit27. Therefore, the purpose of the protocols presented here is to give researchers a quantitative method to assess possible motor deficits as a result of brain trauma following the implantation and persistent presence of intracortical devices (microelectrodes in the case of this manuscript). The behavior tests described here were designed to tease out both gross and fine motor function impairments, and can be used in many models of brain injury. These methods are straightforward, reproducible, and can easily be implemented in a rodent model. Further, the methods presented here allow for a correlation of motor behavior to histological outcomes, a benefit that until recently, the authors have not seen published in the BMI field. Finally, as these methods were designed to test fine motor function28, the gross motor function29, and stress and anxiety behavior29,30, the methods presented here can also be implemented into a variety of head injury models where the researchers want to rule out (or in) any motor function deficits.

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rodent behavioral testing to assess functional deficits caused by microelectrode implantation in the rat motor cortex

Medical devices implanted in the brain hold tremendous potential. As part of a Brain Machine Interface (BMI) system, intracortical microelectrodes demonstrate the ability to record action potentials from individual or small groups of neurons. Such recorded signals have successfully been used to allow patients to interface with or control&#160;computers, robotic limbs, and their own limbs. However, previous animal studies have shown that a microelectrode implantation in the brain not only damages the surrounding tissue but can also result in functional deficits. Here, we discuss a series of behavioral tests to quantify potential motor impairments following the implantation of intracortical microelectrodes into the motor cortex of a rat. The methods for open field grid, ladder crossing, and grip strength testing provide valuable information regarding the potential complications resulting from a microelectrode implantation. The results of the behavioral testing are correlated with endpoint histology, providing additional information on the pathological outcomes and impacts of this procedure on the adjacent tissue.

Using the methods presented here, a microelectrode implantation surgery in the motor cortex is completed following established procedures39,40,41,42, followed by open field grid testing to assess the gross motor function and ladder and grip strength testing to assess the fine motor function27. Motor function testing was completed 2x per w...

Watch this Scientific Journal Video about Rodent Behavioral Testing to Assess Functional Deficits Caused by Microelectrode Implantation in the Rat Motor Cortex at JoVE.com

Rodent Behavioral Testing to Assess Functional Deficits Caused by Microelectrode Implantation in the Rat Motor Cortex

We have shown that a microelectrode implantation in the motor cortex of rats causes immediate and lasting motor deficits. The methods proposed herein outline a microelectrode implantation surgery and three rodent behavioral tasks to elucidate potential changes in the fine or gross motor function due to implantation-caused damage to the motor cortex.

Medical devices implanted in the brain hold tremendous potential. As part of a Brain Machine Interface (BMI) system, intracortical microelectrodes ...

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