Enhancing Cognitive Functions in Aged Rats Through Red Light Stimulation: A Focus on Hippocampal-Thalamic Interaction

Elucidating the mechanisms underlying brain aging and developing strategies to preserve or enhance cognitive abilities in aged rodents are central aims of both fundamental and translational neuroscience research. In this paper, we investigate the effects of red light stimulation (RLS) on enhancing learning and memory capabilities in aged rats, focusing on the interaction between the hippocampus, the anterior thalamus, and the dynamics of interstitial fluid (ISF) within the brain’s extracellular space (ECS). The experimental design included three groups: a light-treated group, a sham stimulation group, and a blank control group. Rats in the light-treated group were exposed to 638 nm red light for seven consecutive days. Additionally, electrodes were implanted in all groups to collect local field potential (LFP) data, and a water maze test was conducted to assess learning and memory capabilities. Behavioral results demonstrated that the light-treated group exhibited significantly improved efficiency in locating the hidden platform and recalling its spatial location in the water maze test. These cognitive enhancements were paralleled by increased ISF diffusion in the hippocampus, suggesting that RLS may facilitate better clearance of metabolic waste and improve neural communication within this region. LFP analysis revealed significant phase coupling synchrony between the hippocampus and thalamus following illumination, indicating a strengthened interaction between these regions. However, these effects diminished five days after the cessation of RLS exposure. In contrast, frequency coupling between the hippocampus and prefrontal cortex, as well as between the thalamus and prefrontal cortex, did not exhibit notable changes. These results suggest that the primary influence of RLS may be localized to the hippocampal-thalamic pathway, potentially mediated through enhanced ISF dynamics within the ECS. This research provides a substantial experimental foundation for the potential application of RLS to augment cognitive functions in the elderly and offers new insights into the role of the anterior thalamic nuclei and ECS in episodic memory, presenting valuable directions for future studies.