[Mechanisms of intrinsically photosensitive retinal ganglion cells regulating learning and memory: a review].

Abstract

Intrinsically photosensitive retinal ganglion cells (ipRGCs) regulate multiple memory-related brain regions via subtype-specific projections. Rodent studies have demonstrated that the effects of light on learning and memory are highly dependent on light-dark cycle, wavelength, intensity, and duration, and are predominantly mediated by the ipRGC-dependent non-image-forming visual pathway. Multiple known and potential regulatory mechanisms have been uncovered to date. The ipRGC→SCN^VIP pathway mediates photo-entrainment of circadian rhythms, and circadian rhythm alterations consequently modulate memory performance. Acute light exposure suppresses the activity of oxytocin-producing neurons through the ipRGC→pSON^GABA→SON^OXT pathway, thereby impairing social memory. Light signals in early developmental stages can shape juvenile development via the ipRGC→SON^OXT→PVN^OXT pathway, which further influences learning capacity in adulthood. Bright-light therapy enhances spatial memory and elevates hippocampal γ-oscillation power by activating the ipRGC→vLGN/IGL^CaMKII→Re pathway. Moderate-intensity light facilitates spatial memory through the CeA^CRH→LC^TH→DG^CaMKIIα pathway, in which norepinephrine released from the LC is involved. Although direct ipRGC projections to the CeA have been validated, the direct modulatory effect of ipRGCs on this pathway remains to be elucidated. In human studies, daytime blue-light exposure and 40 Hz rhythmic blue-light flicker can strengthen visual and auditory working memory and facilitate memory consolidation by activating ipRGC-related pathways, accompanied by prefrontal cortex activation and enhanced hippocampal-thalamic functional connectivity, which reveals promising non-pharmacological potential for memory modulation. Beyond healthy subjects, blue-light intervention also exhibits therapeutic potential for neuropsychiatric disorders. Nevertheless, its clinical translation still requires further standardization of light parameters, development of diurnal and primate animal models, improvement of ipRGC subtype-selective manipulation techniques, as well as long-term stratified clinical studies stratified by age, disease phenotype and memory type, so as to advance the application of intelligent lighting environments and precise phototherapeutic interventions.