The long-term objective of this proposal is to provide strong supporting evidence for an """"""""ontogenetic hypothesis"""""""" of the function of REMS, namely, that REMS plays a significant role in the maturational development of the central nervous system. In the nearly 40 years since REMS was first described, much has been learned regarding the mechanisms that generate and sustain REMS as well as its phenomenology and impact on neurophysiological, metabolic, endocrine and pathological processes. However, to date, nothing is known with certainty about the function or functional consequences of this activated state and why different species have more or less of it. This is especially surprising considering the abundant amounts of time typically devoted to this sleep phase, particularly during early life: the phase of neonatal maturation and development when REMS amounts are maximal. The """"""""ontogenetic REMS hypothesis"""""""" views the REMS state as making a critical, early contribution of stimulation and activation to those integrated, """"""""activity-dependent"""""""" developmental processes known to operate in a number of CNS areas during their critical developmental periods. The preprogrammed intrinsic input to the immature brain, in synergy with extrinsic stimulation, the applicant believes, enables and supports the structural and neurophysiological changes essential to normal CNS development. The applicant has chosen the developing mammalian visual system as a model for testing the hypotheses. Alterations in typical visual experience are required to reveal the physiological and anatomical mechanisms of operation inherent in normal maturational development within the visual system. First altering visual experience, utilizing monocular and binocular visual occlusion during the critical periods of CNS plasticity, the applicant then introduces manipulations that decrease or increase availability of the REMS state. The timing and dependent measures in the studies will permit the applicant to demonstrate distinctly additional and perhaps independent effects deriving solely from the REMS alterations. The effects of varying interactions of altered, early-visual experience with changes in amounts of REMS on visual system development will be assessed, utilizing what have become standard anatomical measures of development in this system: namely, the size of cells in the eye-specific layers of the lateral geniculate nucleus (LGN) and the dimensions of the eye-specific territories occupied in visual cortex by LGN relay-cell terminals.

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National Institute of Neurological Disorders and Stroke (NINDS)
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Behavioral Neuroscience Review Committee (BNR)
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University of Mississippi Medical Center
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Shaffery, James P; Lopez, Jorge; Roffwarg, Howard P (2012) Brain-derived neurotrophic factor (BDNF) reverses the effects of rapid eye movement sleep deprivation (REMSD) on developmentally regulated, long-term potentiation (LTP) in visual cortex slices. Neurosci Lett 513:84-8
Wallace, K L; Lopez, J; Shaffery, J P et al. (2010) Interleukin-10/Ceftriaxone prevents E. coli-induced delays in sensorimotor task learning and spatial memory in neonatal and adult Sprague-Dawley rats. Brain Res Bull 81:141-8
Lopez, J; Roffwarg, H P; Dreher, A et al. (2008) Rapid eye movement sleep deprivation decreases long-term potentiation stability and affects some glutamatergic signaling proteins during hippocampal development. Neuroscience 153:44-53
Allard, Joanne S; Tizabi, Yousef; Shaffery, James P et al. (2007) Effects of rapid eye movement sleep deprivation on hypocretin neurons in the hypothalamus of a rat model of depression. Neuropeptides 41:329-37
Shaffery, James P; Lopez, Jorge; Bissette, Garth et al. (2006) Rapid eye movement sleep deprivation in post-critical period, adolescent rats alters the balance between inhibitory and excitatory mechanisms in visual cortex. Neurosci Lett 393:131-5
Shaffery, James P; Lopez, Jorge; Bissette, Garth et al. (2006) Rapid eye movement sleep deprivation revives a form of developmentally regulated synaptic plasticity in the visual cortex of post-critical period rats. Neurosci Lett 391:96-101
Shaffery, James; Hoffmann, Robert; Armitage, Roseanne (2003) The neurobiology of depression: perspectives from animal and human sleep studies. Neuroscientist 9:82-98
Shaffery, J P; Sinton, C M; Bissette, G et al. (2002) Rapid eye movement sleep deprivation modifies expression of long-term potentiation in visual cortex of immature rats. Neuroscience 110:431-43
Shaffery, J P; Roffwarg, H P; Speciale, S G et al. (1999) Ponto-geniculo-occipital-wave suppression amplifies lateral geniculate nucleus cell-size changes in monocularly deprived kittens. Brain Res Dev Brain Res 114:109-19
Marks, G A; Roffwarg, H P; Shaffery, J P (1999) Neuronal activity in the lateral geniculate nucleus associated with ponto-geniculo-occipital waves lacks lamina specificity. Brain Res 815:21-8

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