- Identifying circadian factors during middle age that increase risk for later-life cognitive impairment
- Developing novel, light-based treatments to stem loss of cognition during aging
- Establishing basic principles for how circadian function shapes memory processing
Our circadian profile, the relationship across time between our body's internal clock and the natural 24-hour schedule of light produced by the earth's rotation about its axis, shapes our biological fabric: how we develop, thrive, and ultimately decline. My laboratory uses animal models to define individual differences in circadian function that are likely to impact memory performance as people age. Episodic memory loss is one of the earliest features of cognitive, age-related disease and is often correlated with flattening of the circadian activity rhythm (CAR) amplitude and high CAR fragmentation. Based on my findings, I hope to characterize biomarkers that will identify 'midlife' individuals at risk for later Alzheimer's or vascular dementia, the two most common brain diseases affecting the elderly.
A natural bedfellow to these efforts will be efforts to understand how the non-visible and visible light spectrum can be exploited to rehabilitate chronic circadian dysrhythmia. The eye uses a photoreceptor system to process circadian timing that is independent of the one it uses for visual perception. Unfortunately, little is known about the logic by which it does so. My laboratory will draw from the comparative biology literature to understand what features of naturally occurring daytime/nighttime light most influence the circadian pacemaker, and—with data we empirically collect—will put together a basic “programming language” for how to deliver light pulses to strengthen the pacemaker's operation. Our long-term goal will be to embody this programming language in a small medical device that can give rhythms and cognition back to an unhealthy person while they are asleep.
Fernandez F., Lu D., Ha P., Costacurta P., Heller H.C., and Ruby N.F. (2014). Dysrhythmia in the suprachiasmatic nucleus inhibits memory processing. Science, 346, 854-857. PMID: 25395537
Ruby N.F.*, Fernandez F.*, Zhang P., Klima J., Heller H.C., and Garner C.C. (2010). Circadian locomotor rhythms are normal in Ts65Dn "Down Syndrome" mice and unaffected by Pentylenetetrazole. Journal of Biological Rhythms, 25, 63-66. *Co-Primary Authors. PMID: 20075302
Ruby N.F., Hwang C.E., Wessells C., Fernandez F., Zhang P., Sapolsky R., and Heller H.C. (2008). Hippocampal-dependent learning requires a functional circadian system. Proceedings of the National Academy of Sciences, 105, 15593-15598. PMID: 18832172
Fernandez F. and Garner C.C. (2007). Over-inhibition: a model for developmental intellectual disability. Trends in Neurosciences, 30, 497-503. PMID: 17825437
Fernandez F., Morishita W., Zuniga E., Nguyen J., Blank M., Malenka R.C., and Garner C.C. (2007). Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome. Nature Neuroscience, 10, 411-413. PMID: 17322876