Marcos G. Frank
Marcos G. Frank, Ph.D.
University of Pennsylvania
School of Medicine
Philadelphia, PA 19104-6060
Fax: (215) 573-9050
Stanford University, 1997.
Description of Research ExpertiseRESEARCH INTERESTS
The regulation and function of sleep in developing and adult animals. The of experience and offline processes in brain plasticity. The role of glia in sleep regulation and function.
neural development, sleep, synaptic plasticity, glia
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 include immunohistochemistry, Western blot assays and qPCR.
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 we are 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.
Selected PublicationsFrank, M.G., Issa, N.P. and Stryker, M.P.: Sleep enhances plasticity in developing visual cortex. Neuron 30: 275-287, 2001.
Jha, S.K., Jones, B.E., Coleman, T., Steinmetz, N., Law, C.T., Griffin, G., Hawk, J., Dabbish, N., Kalatsky, V.A. and Frank, M.G.: Sleep-dependent plasticity requires cortical activity. Journal of Neuroscience 25(40): 9266-9274, August 2005.
Hallasa M, Florian C, Fellin T, Munoz JR, Abel T, Haydon P, and Frank MG: Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss. Neuron 61(2): 213-219, January 29 2009.
Aton S, Seibt J, Dumoulin M, Jha SK, Steinmetz N, Coleman T, Naidoo N, Frank MG: Mechanisms of sleep-dependent consolidation of cortical plasticity. Neuron 61(3): 454-466, February 12 2009.
Seibt J, Aton S, Jha SK, Dumoulin M, Coleman C, Frank MG: The non-benzodiazepine hypnotic zolpidem impairs sleep-dependent cortical plasticity SLEEP 31: 1381-1392, 2008.
Frank, M.G.: Sleep, synaptic plasticity and the developing brain. Sleep, circuits and functions. P. Luppi (eds.). CRC Press, Page: 177-193, 2004.
Frank MG, Benington J: The role of sleep in brain plasticity: dream or reality? The Neuroscientist 12: 477-488, 2006.
Frank, M. G.and Stryker, M. P.: The role of sleep in the development of central visual pathways. Sleep and Brain Plasticity. P. Maquet and R. Stickgold (eds.). Oxford Press, United Kingdom, Page: 189-106, 2003.
Benington, J. and Frank, M.G.: Cellular and molecular connections between sleep and synaptic plasticity. Progress in Brain Research 69: 71-101, 2003.