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

Abstract

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.

Morris water maze: a versatile and pertinent tool for assessing spatial learning and memory

“…As for MWM flexibility in assessing working memory, where the platform is placed in new positions every day [ 13 ], this is not as sensitive as other mazes and has not been widely used as such [ 18 ]. Instead, a six- or eight-armed radial arm water maze (RAWM), first conducted by [ 194 ], which is a modification and combination of RAM and MWM, has been proven to provide a more robust measure to assess working memory such as in traumatic brain injury or an Alzheimer’s animal model [ 195 , 196 , 197 ]. However, in comparison to the MWM, it remains more challenging to track the animal’s swimming trajectory in the RAWM because the animal movement is confined to the maze alley, which may be disadvantageous in the context of this modified version.…”

Roadbumps at the Crossroads of Integrating Behavioral and In Vitro Approaches for Neurotoxicity Assessment

“…The radial arm maze (RAM) is an 8-arm maze that can be used either dry (e.g., food reinforcement) or submerged in water [e.g., escape from water ( Penley et al, 2013 ; Macheda et al, 2020 )] to assess spatial working memory and reference memory. Various procedures exist using the RAM.…”