Light modulates hippocampal function and spatial learning in a diurnal rodent species: A study using male nile grass rat (Arvicanthis niloticus)

Abstract

The effects of light on cognitive function have been well-documented in human studies, with brighter illumination improving cognitive performance in school children, healthy adults, and patients in early stages of dementia. However, the underlying neural mechanisms are not well understood. The present study examined how ambient light affects hippocampal function using the diurnal Nile grass rats (Arvicanthis niloticus) as the animal model. Grass rats were housed in either a 12:12 h bright light-dark (brLD, 1,000 lux) or dim light-dark (dimLD, 50 lux) cycle. After 4 weeks, the dimLD group showed impaired spatial memory in the Morris Water Maze (MWM) task. The impairment in their MWM performance were reversed when the dimLD group were transferred to the brLD condition for another 4 weeks. The results suggest that lighting conditions influence cognitive function of grass rats in a way similar to that observed in humans, such that bright light is beneficial over dim light for cognitive performance. In addition to the behavioral changes, grass rats in the dimLD condition exhibited reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus, most notably in the CA1 subregion. There was also a reduction in dendritic spine density in CA1 apical dendrites in dimLD as compared to the brLD group, and the reduction was mostly in the number of mushroom and stubby spines. When dimLD animals were transferred to the brLD condition for 4 weeks, the hippocampal BDNF and dendritic spine density significantly increased. The results illustrate that not only does light intensity affect cognitive performance, but that it also impacts hippocampal structural plasticity. These studies serve as a starting point to further understand how ambient light modulates neuronal and cognitive functions in diurnal species. A mechanistic understanding of the effects of light on cognition can help to identify risk factors for cognitive decline and contribute to the development of more effective prevention and treatment of cognitive impairment in clinical populations.

Keywords: brain-derived neurotrophic factor; diurnal; hippocampus; light; synaptic plasticity.

Figure 1

Impaired MWM performance of grass rats housed in dimLD compared to those in brLD condition over 4 weeks. (A) Latency of animals to locate the platform during trial 1 (24-hour delay) over the 5 training days. Grass rats housed in brLD were able to locate the platform significantly faster in the than those housed in dimLD (main effect of training days: F(4,56)= 16.493, p<0.001; main effect of lighting condition: F(1,14)=4.652, p< 0.05); interaction between training days and lighting condition (F(4,56)= 0.953, p>0.05). (B) Latency of animals to locate the platform during trial 2 (30-second delay), there were no significant differences between the two groups. (C) Representative track plots of a grass rat in each lighting condition during the probe trial (with goal quadrant highlighted). (D). Grass rats housed in brLD nearly spent twice as much amount of time searching for the platform in the goal quadrant in the probe test when compared to grass rats in the dimLD group. *, p < 0.05.

Figure 2

Subsequent brLD housing (dim-brLD) restored the impaired MWM performance of animals housed in dimLD conditions for 4 weeks. (A) Latency of animals to locate the platform during the first trial (main effect of training days: (F(4,56)= 15.05, p<0.001); main effect of housing condition : (F(1,14)= 12.942, p= 0.003); interaction between training days and housing condition: F(4,56)= 2.38, p= 0.062). (B) Latency of animals to locate the platform during the 2nd trial, there were no significant differences between the two groups. (C) Representative track plots of a grass rat in each lighting condition during the probe trial (with goal quadrant highlighted). (D). Time spent searching for the platform in the goal quadrant in the probe test. *, p < 0.05.

Figure 3

Ambient light condition modulates hippocampal BDNF expression. (A) Representative photomicrographs of BDNF immunochemical staining within the CA1, CA3, and DG of the hippocampus of grass rats housed in brLD or dimLD condition. (B) Number of BDNF-labeled cell bodies in each subregion of the hippocampus in animals housed in brLD or dimLD condition. (C). Number of BDNF-labeled cell bodies in each subregion of the hippocampus in animals housed in dimLD and those initially housed in dimLD then switched to brLD. Scale bar, 100 μm. *, p<0.05; **, p < 0.01; ***, p < 0.001.

Figure 4

Golgi staining of CA1 apical dendrites. (A) Representative photomicrograph and (B) quantification of dendritic spines of grass rats housed in either brLD or dimLD condition for 4 weeks. (C) Representative photomicrograph and (D) quantification of dendritic spines of grass rats housed in dimLD or initially in dimLD then transferred to brLD. Scale bar, 5μm. *, p < 0.01; **, p < 0.001.

Figure 5

Hippocampal apical dendrites visualized by HSV-GFP expression. (A) The injection sites of the HSV-GFP. (B) Representative photomicrophs of HSV-GFP expression. (C) Quantification of the density of dendritic spine sub-types. Scale bar, 5μm. *, p < 0.01.