Brain Maturation: Function for Rapid Eye-Movement Sleep

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EXCEED THE SPACE PROVIDED. The long-term goal of this project is to determine whether rapid eye movement sleep (REMS) has a.function in early life as one part of a genetically programmedgroup of CNS processes that guide and establish the maturational development of the brain. This hypothesis was oiiginally suggested by several characteristics of REMS: It is a more highly represented state of the mammalian CNS in the late fetal, neonatal and early infancy periods than inthe adult, particularly in altricial species in which significant CNS development continues for a time after birth; it decreases in early development relative to the two other CNS states (non-REMS and waking) as the period of maximal brain growth ebbs, and it is a time of intense neuronalanc metabolic activation of widespread CNS areas by endogenous impulses generated from centers withinthe brain. Thisproposec early CNS function, or functional consequence, of REMS state-related activation exemplifies the well accepted principleo: activity-dependent development cf neural tissue. In terms of this model of CNS development, the role of REMS isdesignec to operate synergistically with other endogenous processes and be additive and complementary in its actions with exogenous arocesses to direct and potentiate normal (usual) brain development. Having gathered evidence in our first project period tha removal of REMS in young mammals by REMS-deprivation techniquessignificantly affects lateral geniculate nucleus (LGN ;ell size, we now aim to uncover the direct effects of REMS-related activation. During REMS, repetitive phasic discharges ponto-geniculo-occipital (PGO)--waves, are generated in brainstemand arc concomitant with activation inmany brain areas. We lave preliminary evidence and new seek to validate that this phasic activating component of REMS is a key process exerting the effects of REMS on neural development. We will depriveREMS and associated PGO-waves but also then evoke, withlouc tones an experimental replicate of the PGO-wave exclusivelyduringwaking-in-the-dark to test whether the replacementPGO- waves counteract alterations in LGN cell size being induced by ongoing REMS-deprivation in monocularlydeprivedanimals The REMS state is a confluence of properties which control neuronal activity and may affect LGN cell size through known mechanisms of activity-dependent synaptic plasticity. Our second set of studiestests whether a specificglutamate receptor that is known to be essential to activity-dependent development is also necessary to the developmental effects of REMS. We test this hypothesis by infusing a glutamate receptor antagonist into visual cortex to block our demonstrated, and, expected effects of REMS deprivation on geniculocortical cell development in animals experiencing ongoing visual asymmetry. Increasing our understanding of the mechanisms associated with the hypothesized developmental function of REMS may enable prevention and treatment of certain sleep and depression pathologies. PERFORMANCE SITE ========================================Section End===========================================