Journal Article

Optimization and validation of a modified radial-arm water maze protocol using a murine model of mild closed head traumatic brain injury

Macheda, Teresa, Bachstetter, Adam D., Braun, David J., Roberts, Kelly N., Morganti, Josh M.

2020

Overview

Cognitive impairments can be a significant problem after a traumatic brain injury (TBI), which affects millions worldwide each year. There is a need for establish reproducible cognitive assays in rodents to better understand disease mechanisms and to develop therapeutic interventions towards treating TBI-induced impairments. Our goal was to validate and standardize the radial arm water maze (RAWM) test as an assay to screen for cognitive impairments caused by TBI. RAWM is a visuo-spatial learning test, originally designed for use with rats, and later adapted for mice. The present study investigates whether test procedures, such us the presence of extra-maze cues influences learning and memory performance. C57BL/6 mice were tested in an 8-arm RAWM using a four-day protocol. We demonstrated that two days of training, exposing the mice to extra-maze cues and a visible platform, influenced learning and memory performance. Mice that did not receive training performed poorer compared to mice trained. To further validate our RAWM protocol, we used scopolamine. We, also, demonstrated that a single mild closed head injury (CHI) caused deficits in this task at two weeks post-CHI. Our data supported the use of 7 trials per day and a spaced training protocol as key factor to unmask memory impairment following CHI. Here, we provide a detailed standard operating procedure for RAWM test, which can be applied to a variety of mouse models including neurodegenerative diseases and pathology, as well as when pharmacological approaches are used.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aging / Animal experimentation / Animal models / Biology and Life Sciences / Brain / Brain injuries / Brain research / Cognitive ability / Cognitive disorders / Complications and side effects / Development and progression / Diagnosis / Experiments / Head injuries / Laboratory animals / Learning / Maze learning / Medicine and Health Sciences / Memory / Methods / Mice / Neurodegenerative diseases / Neurosciences / Optimization / Research and Analysis Methods / Scopolamine / Social Sciences / Spatial discrimination learning / Spatial memory / Spinal cord / Test procedures / Therapeutic applications / Training / Traumatic brain injury