Sleep occupies one-third of our adult lives and yet we still do not know its function. As surprising as this may seem, consider that sleep occupies over two-thirds of the daily lives of infants and yet the vast majority of sleep research concerns its phenomenology and function in adults. Moreover, controversy still surrounds the nature of infant sleep, its relationship to adult sleep, and its neural substrates. A guiding theme of this proposal is that a satisfactory explanation of sleep development, and ultimately sleep's function, will emerge most readily from focused, mechanistic investigations of individual sleep components and their associated neural circuitry during infancy. Two components of active (REM) sleep are nuchal muscle atonia and myoclonic twitching, which together help to define a coherent sleep state in infant rats. It was found recently that 2-day-old (P2) rats cycle rapidly between sleep and wakefulness and that these cycles lengthen significantly over the first postnatal week. Building on this finding, the modulation of sleep cyclicity by circadian factors, moderate and extreme cold exposure, and food deprivation will be investigated. In addition, a novel method for depriving infants of sleep is proposed. These experiments are essential to describe fully the factors that modulate normal sleep in the developing infant and to evaluate the infant's ability to regulate sleep homeostatically. Next, neurophysiological and selective lesioning techniques will be used to explore the neural mechanisms that contribute to sleep cycle development between P2 and P8, as well as a second transition that occurs between P10 and P15. This second transition covers a period characterized by the development of slow-wave sleep (SWS), the second major category of sleep. Specific hypotheses concerning the neural mechanisms that modulate these transitions will be tested in unanesthetized and unrestrained infant rats using multisite electrodes implanted into mesopontine, thalamic, hypothalamic, and forebrain structures implicated in the control of sleep in adults. All together, the experiments proposed here address basic issues in sleep development that have not been systematically explored. It is expected that a more thorough understanding of the development of sleep will provide useful insights into the causes and treatment of sleep and developmental disorders in preterm and full-term infants, as well as adults.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH050701-12
Application #
7162085
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Vicentic, Aleksandra
Project Start
1994-05-01
Project End
2009-12-31
Budget Start
2007-01-01
Budget End
2007-12-31
Support Year
12
Fiscal Year
2007
Total Cost
$251,743
Indirect Cost
Name
University of Iowa
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Blumberg, Mark S (2017) Development evolving: the origins and meanings of instinct. Wiley Interdiscip Rev Cogn Sci 8:
Gall, Andrew J; Todd, William D; Blumberg, Mark S (2012) Development of SCN connectivity and the circadian control of arousal: a diminishing role for humoral factors? PLoS One 7:e45338
Karlsson, K A E; Arnardóttir, H; Robinson, S R et al. (2011) Dynamics of sleep-wake cyclicity across the fetal period in sheep (Ovis aries). Dev Psychobiol 53:89-95
Mohns, Ethan J; Blumberg, Mark S (2010) Neocortical activation of the hippocampus during sleep in infant rats. J Neurosci 30:3438-49
Seelke, Adele M H; Blumberg, Mark S (2010) Developmental appearance and disappearance of cortical events and oscillations in infant rats. Brain Res 1324:34-42
Marcano-Reik, Amy Jo; Prasad, Tuhina; Weiner, Joshua A et al. (2010) An abrupt developmental shift in callosal modulation of sleep-related spindle bursts coincides with the emergence of excitatory-inhibitory balance and a reduction of somatosensory cortical plasticity. Behav Neurosci 124:600-11
Todd, William D; Gibson, James L; Shaw, Cynthia S et al. (2010) Brainstem and hypothalamic regulation of sleep pressure and rebound in newborn rats. Behav Neurosci 124:69-78
Gall, Andrew J; Joshi, Badal; Best, Janet et al. (2009) Developmental emergence of power-law wake behavior depends upon the functional integrity of the locus coeruleus. Sleep 32:920-6
Marcano-Reik, Amy Jo; Blumberg, Mark S (2008) The corpus callosum modulates spindle-burst activity within homotopic regions of somatosensory cortex in newborn rats. Eur J Neurosci 28:1457-66
Mohns, Ethan J; Blumberg, Mark S (2008) Synchronous bursts of neuronal activity in the developing hippocampus: modulation by active sleep and association with emerging gamma and theta rhythms. J Neurosci 28:10134-44

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