The function
of sleep in developing and adult animals.
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.
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 are also investigating if sleep has similar effects on synaptic
plasticity in adult animals.
We are also
interested in examining the consequences of abnormal sleep development
on brain development and behavior. This is an area of research
that is relatively unexplored, but one with profound clinical
implications. For example, sudden infant death syndrome (SIDS)
is the one of the leading causes of infant mortality in the United
States. While SIDS is associated with abnormal sleep and autonomic
function, the precise mechanisms responsible for SIDS are poorly
understood. We are currently investigating SIDS by studying sleep
patterns in infant animals perinatally exposed to compounds known
to increase the occurrence of SIDS in humans, in the hopes of
identifying these mechanisms.
Frank, M. G., Morrissette, R., Heller, H. C. (1998) Effects of sleep deprivation in neonatal rats. Am. J. Physiol. 275: R148-R157.
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. and Stryker, M.P. The role of sleep in the development of central visual pathways. In: Sleep and brain plasticity, edited by Maquet P, Smith C and Stickgold R. New York: Oxford University Press, 2003, p. 189-206.
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. Online PDF File
