Overstimulation of newborn mice leads to behavioral differences and deficits in cognitive performance

Abstract

Observational studies in humans have found associations between overstimulation in infancy via excessive television viewing and subsequent deficits in cognition and attention. We developed and tested a mouse model of overstimulation whereby p10 mice were subjected to audio (70 db) and visual stimulation (flashing lights) for six hours per day for a total of 42 days. 10 days later cognition and behavior were tested using the following tests: Light Dark Latency, Elevated Plus Maze, Novel Object Recognition, and Barnes Maze. In all tests, overstimulated mice performed significantly worse compared to controls suggesting increased activity and risk taking, diminished short term memory, and decreased cognitive function. These findings suggest that excessive non-normative stimulation during critical periods of brain development can have demonstrable untoward effects on subsequent neurocognitive function.

Figure 1. Mouse overstimulation chamber, and experimental procedure.

Figure 2. Results of Elevated Plus Maze (EPM) and Light Dark Latency (LDL) Tests.

2A & 2B demonstrate an illustrative example of a control and an overstimulated mouse's travel pathway on the EPM. Overstimulated mice spent more time in the open arm (mean±SEM; Controls: 9.93±2.11s, n = 48 and Overstimulated: 31.03±2.78s, n = 61, p < 0.001). (2E); had more entries in the open arms (mean±SEM; Controls: 7.97±1.22, n = 48 and Overstimulated: 11.92±1.06, n = 61, p < 0.001). (2F); and traveled greater distances in the open arms (mean±SEM; Controls: 73.55±23.61cm, n = 48 and Overstimulated: 176.23±14.62cm, n = 61, p < 0.001). (2G). 2C & 2D demonstrate an illustrative example of a control and an overstimulated mouse's travel pathway on the LDL. Overstimulated mice spent more time in the light chamber (mean±SEM; Controls: 53.79±4.17s, n = 48 and Overstimulated: 82.39±6.41s, n = 61, p < 0.001) (2H); took less time to fully enter the light chamber (mean±SEM; Controls: 223.00±17.49s, n = 48 and Overstimulated: 98.00±15.33, n = 61, p < 0.001) (2I) and traveled greater distances in the light chamber (mean±SEM; Controls: 276.42±42.03cm, n = 48 and Overstimulated: 436.89±40.06cm, n = 61, p <0.05) (2J).

Figure 3. Results of Open Field Test: Tests.

3A & 3B demonstrate an illustrative example of a control and an overstimulated mouse's travel pathway on the Open Field Test. Overstimulated mice spent more time in the center of the open field (mean±SEM; Controls: 24.97±2.04, n = 64 and Overstimulated: 44.25±3.76, n = 72, p < 0.001) (3C), had more entries into the center of the open field (mean±SEM; Controls: 20.69±1.72, n = 72 and Overstimulated: 34.94±2.72, n = 72, p < 0.001) (3D), and they were more active as measured in distance traveled in the center of the open field field (mean±SEM; Controls: 505.79±47.45, n = 72 and Overstimulated: 883.03±71.82, n = 72, p <0.001), (3E) They also traveled greater distance overall (mean±SEM; Controls: 5836.66±194.26, n = 72 and Overstimulated: 6612.43±200.5, n = 72, p< 0.001) (3F).

Figure 4. Results of Barnes Maze Test (BM) and Novel Object Recognition Test (NORT).

4A & B demonstrate an illustrative example of a control and an overstimulated mouse's travel pathway on the BM. 4C summarizes the results of the BM over 4 days of successive testing. Overstimulated mice trended towards finding the escape hole faster than controls during the first day of the experiments (mean±SEM; Controls: 30.60±4.64, n = 12 and Overstimulated: 20.08±2.35, n = 72, p = 0.09) which is consistent with our findings that exposed animals travel greater distances, and thus are more likely to encounter the escape hole. However, on day 4, control mice took significantly less time to find the target hole compared to overstimulated mice (mean±SEM; Controls: 3.44±0.39, n = 12 and Overstimulated: 6.33±0.67, n = 10, p < 0.001) Overstimulated mice continued to make more errors before finding the hole suggesting impaired memory and learning. Figure 4D summarizes the mean times mice spent on both objects during the acquisition (mean±SEM; Controls: 44.35±4.61, n = 39 and Overstimulated: 57.49±4.01, n = 42), and the test trial (mean±SEM; Controls: 44.87±5.64, n = 39 and Overstimulated: 53.81±3.77, n = 42). Figure 4E shows the discrimination ratio for the controls and the overstimulated mice. This shows how well the mice were able to discriminate between the novel and the familiar object. Overstimulated mice spent less time with a novel object compared to controls. Accordingly the discrimination ratio calculated as ((Time Spent on the Novel Object – Time Spent On the Familiar Object)/Total Time) is significantly reduced compared to controls (mean±SEM; Controls: 0.32±0.07, n = 39 and Overstimulated: 0.16±0.05, n = 42, p < 0.05).