Description of Research Expertise

KEY WORDS:
neural development, sleep, cortical plasticity

RESEARCH INTERESTS
The 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.

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 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.