Assessment of Cognitive Function in the Water Maze Task: Maximizing Data Collection and Analysis in Animal Models of Brain Injury

Abstract

Animal models play a critical role in understanding the biomechanical, pathophysiological, and behavioral consequences of traumatic brain injury (TBI). In preclinical studies, cognitive impairment induced by TBI is often assessed using the Morris water maze (MWM). Frequently described as a hippocampally dependent spatial navigation task, the MWM is a highly integrative behavioral task that requires intact functioning in numerous brain regions and involves an interdependent set of mnemonic and non-mnemonic processes. In this chapter, we review the special considerations involved in using the MWM in animal models of TBI, with an emphasis on maximizing the degree of information extracted from performance data. We include a theoretical framework for examining deficits in discrete stages of cognitive function and offer suggestions for how to make inferences regarding the specific nature of TBI-induced cognitive impairment. The ultimate goal is more precise modeling of the animal equivalents of the cognitive deficits seen in human TBI.

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“…These changes could not be ascribed to an alteration of the general motor activities secondary to the injection or the treatment since no differences were observed among the four groups of mice when the number of entries in each arm of the maze was assessed. In addition, the same treatment resulted in a significant amelioration of their spatial learning and memory as documented in the Morris water maze [30]. Thus, in the probe trial compared with WT the 3xTg mice receiving empty vector had a lower number of platform entry and time spent in the platform zone together with an increase in the latency to first entry, and all of these parameters were improved in the 3xTg mice receiving the AAV-VPS35.…”

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

“…With the knowledge that training schedule and spacing of training sessions can impact learning ability [ 10 – 13 , 24 , 25 ], we sought to determine if reduction of training increased the learning separation between mice affected by mTBI and controls. Our results confirmed that reduction of total number of trials increases the chance to separate learning impairment and this could be critical in a study where new compounds to reverse the injury effect are used [ 37 ] or when a smaller injury effect needs to be discovered [ 37 ]. A significant advantage using our new protocol is that more mice could be tested in one session, reducing time of testing and variability between groups.…”

Validation and standardization of a new radial-arm water maze protocol using a murine model of mild closed head traumatic brain injury

“…However, due to the knowledge that training schedule and spacing of training sessions can impact learning ability [10–13, 24, 25], we sought to determine if reduction of training increased the learning separation between mice affected by mTBI and controls. Our results confirmed that reduction of total number of trials increases the chance to separate learning impairment and this could be critical in a study where new compounds to reverse the injury effect are used [37] or when a smaller injury effect needs to be discovered [37]. A significant advantage using our new protocol is that more mice could be tested in one session, reducing time of testing and variability between groups.…”