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Marcos
Frank, Ph.D.
Assistant Professor, Dept of Neuroscience
111 Johnson Pavilion
Tel: (215) 746-0388
Lab: (215) 746-0389
Fax: (215) 573-9050
Email: mgf@mail.med.upenn.edu
Click here for selected publications since Dr. Frank's arrival at Penn
RESEARCH INTERESTS
The regulation and function of sleep in developing and adult animals.RESEARCH TECHNIQUES
Chronic recording of single and multiple neuron activity combined with infusion of neuroactive compounds in freely moving animals, sleep/wake state analyses in developing and adult animals, measuring and manipulating synaptic plasticity in vivo, optical imaging of intrinsic cortical signals combined with electrophysiological recording in visual cortex. Additional techniques used in our collaborative efforts with Dr.’s Ted Abel and Allan Pack include immunohistochemistry, Western blot assays and qPCR.
.RESEARCH SUMMARY
Among the many unanswered questions in biology, one of the most persistent and perplexing is why animals sleep. Despite great progress in our understanding of the regulation and neurobiology of sleep, as well as the consequences of sleep loss on human performance, why the brain needs sleep remains a mystery.
The mystery of sleep function only deepens when we consider the developing animal. Infant animals spend as much as 80% of their time in sleep, and rather than being a passive response to the environment, infant sleep is an actively regulated state. This suggests that whatever the function of sleep might be, it is something that begins very early in life.
In my laboratory, one way we investigate the mystery of sleep function is by examining the role of sleep in the development of central visual pathways. The visual system is uniquely suited for our studies because many of the basic processes of neural development were first described in this sensory system.
One critical step in visual system development is the establishment of rudimentary circuits in visual cortex; a process that requires endogenous neural activity instead of waking visual experience. Given the large amounts of sleep during this developmental period, we suspect that this activity is provided by the sleeping brain. We are investigating this possibility by recording activity patterns from neurons in visual structures during rapid-eye-movement (REM) and nonREM sleep in developing animals, and determining if these activity patterns contribute to the development of visual cortex.
A second essential stage in visual system development occurs during narrow, 'critical' periods when the brain is exquisitely sensitive to changes in visual experience. The classic studies by Hubel and Wiesel showed that blocking vision in one eye during the critical period resulted in dramatic physiological and anatomical changes in visual cortex.We have previously demonstrated that this well-described form of in vivo plasticity is enhanced by sleep, and we are currently investigating the underlying mechanisms responsible for this effect. We now know that critical cellular steps in this process include a sleep-dependent activation of several kinases and the phosphorylation of cortical AMPA receptors; key steps in potentiating post-synaptic responses.
We are also interested in determining the cellular basis for sleep homeostasis and more specifically, the interactions between the sleep regulation and sleep function. To this end in collaboration with Dr. Phil Haydon at Tufts University, we have been investigating the role of astrocytes in the accumulation and discharge of sleep pressure and synaptic plasticity in vivo. We have shown, for example, that astrocytes are key players in controlling sleepiness in mammals through the release of glio-transmitters. Because astrocytes also influence synaptic plasticity, these cells are uniquely positioned to connect the regulation of sleep with one of its hypothesized functions.
KEY WORDS:
neural development, sleep, cortical plasticity
Key References:
Hallasa, M., Florian, C., Fellin, T., Munoz, J.R., Abel, T., Haydon, P., Frank, M.G. (2009) Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss. Neuron In Press.
Aton, S., Seibt, J., Dumoulin, M., Jha, S.K., Steinmetz, N., Coleman, T., Naidoo, N., Frank , M. G. (2009) Mechanisms of sleep-dependent consolidation of cortical plasticity. Neuron In Press.
Jha, S. K., Jones, B. E., Coleman, T., Steinmetz, N., Law, C.-T., Griffin, G., Hawk, J., Dabbish, N., Kalatsky, V. A., Frank, M. G. (2005) Sleep-dependent plasticity requires cortical activity. Journal of Neuroscience 25:9266-9274.
Frank, M. G., Issa, N. P. Stryker, M. P. (2001) Sleep enhances plasticity in developing visual cortex. Neuron 30:275-287.
Frank, M. G, Srere, H., Ledezma, C., O'Hara, B. F., Heller, H. C. (2001) Prenatal nicotine alters vigilance states and AchR gene expression in the neonatal rat: implications for SIDS. Am. J. Physiol. 280:R1134-R1140.
Frank, M. G., Morrissette, R., Heller, H. C. (1998) Effects of sleep deprivation in neonatal rats. Am. J. Physiol. 275: R148-R157.
