Contribution of Brain Slice Electrophysiology in Neurotoxicity Assessments

Photo By Megan Mudersbach | Dr. Joyce Rohan, research physiologist, is in the Naval Medical Research Unit Dayton’s (NAMRU-Dayton) Environmental Health Effects Lab. Here, Rohan creates lab models to accurately reflect the myriad of environmental conditions Service members may experience.  

WRIGHT-PATTERSON AIR FORCE BASE, OH, UNITED STATES

09.11.2019

Story by Megan Mudersbach 

Naval Medical Research Unit Dayton

By: Dr. Joyce Rohan, Research Physiologist

Detecting cognitive deficits in an animal model can be difficult because they communicate differently than humans. Behavioral assays that assess thinking in animals are complicated to perform, often requiring multiple days, making detection of immediate effects challenging. In addition, these cognitive tests typically cannot be performed on the same animals more than once and thus additional sets of animals are needed to evaluate effects at multiple time points after exposures. Electrophysiology offers an alternative approach for detecting cognitive effects by directly measuring the electrical activity of neurons that are essential for cognition.

At the Naval Medical Research Unit Dayton’s (NAMRU-Dayton) Environmental Health Effects Laboratory, we have incorporated electrophysiology using brain slice in conjunction with biochemical measurements and behavioral testing for our neurotoxicity studies. We currently have five funded projects in which brain slice electrophysiology plays a prominent role in characterizing exposure effects on the central nervous system. Those projects involve exposures ranging from chemicals routinely used during the Gulf War to extreme temperatures. Most of our brain slice electrophysiology studies focus on the hippocampus, a region of the brain essential for cognitive processes such as learning and memory. The contribution of this electrophysiology is to aid in the detection of subtle changes in neuronal function within the hippocampus that can lead to cognitive impairments. Our microelectrode array system is capable of delivering electrical stimulations and thus can be used to evaluate not only spontaneous neuronal activity but also synaptic transmission (communication among neurons) and synaptic plasticity (the ability of neurons to change strength of their contribution), both of which are absolutely essential for cognitive processes.

Using brain slice electrophysiology, we have found that different chemicals induced distinct changes in neurons within the hippocampus. For example, exposure to chemicals commonly used during the Gulf War induced reduction in the synaptic transmission, an enhancement of paired pulse facilitation which is a measure of short-term synaptic plasticity, and a reduction in spontaneous activity. A separate study showed that exposures to aluminum chloride induced a reduction in long-term potentiation which is a measure of long-term synaptic plasticity, likely indicating an impairment in learning and memory. We are currently addressing the question of which electrophysiological parameters can be correlated with cognitive impairment. In addition, NAMRU-Dayton also has an in vivo electrophysiology system that enables the recording of neuronal activity in a live, freely moving animal so that we can record neuronal activities at multiple time points in the same animal. NAMRU-Dayton also has a patch clamp electrophysiology system that enables the recording of single neurons so that we can gather insight into the pathways that are triggered inside of cells as a result of exposure to chemicals or other stressors.

Together with our existing biochemical and animal behavioral capabilities, the addition of electrophysiology in our neurotoxicity toolbox has equipped us to better understand threats to Service members and therefore protect them against potential neurotoxic hazards.

• Date Taken: 09.11.2019
• Date Posted: 09.11.2019 17:24
• Story ID: 339918
• Location: WRIGHT-PATTERSON AIR FORCE BASE, OH, US