Brain Maturation: Function for Rapid Eye-Movement Sleep

超出提供的空间。该项目的长期目标是确定快速眼动睡眠(REMS)在早期生命中是否具有某种功能，作为引导和建立大脑成熟发育的一组中枢神经系统过程的一部分。这一假说是由REMS的几个特征提出的：它是哺乳动物CNS在胎儿晚期、新生儿和婴儿期早期的一种比成年更具代表性的状态，特别是在出生后仍有一段时间显著发育的原始物种中；它在早期发育中相对于其他两种CNS状态(非REMS和清醒状态)减少，作为大脑生长的最大衰退期，并且这是大脑中心产生的内源性冲动对广泛的CNS区域进行神经代谢激活的强烈时期。这一提出的REMS状态相关激活的早期中枢功能或功能结果例证了公认的原则：神经组织的活动依赖发育。根据这一中枢神经系统发育模型，RMS的作用被设计为与其他内源性过程协同运行，并与外源性ARC相加和互补，以指导和加强正常(通常)的脑发育。在我们的第一个项目期间收集了证据表明，通过剥夺REMS技术移除年轻哺乳动物的REMS会显著影响外侧膝状核(LGN；细胞大小)，现在我们的目标是揭示REMS相关激活的直接影响。在REMS过程中，在大脑中产生重复的相放电--膝枕(PGO)波，并伴有多个脑区的激活。我们提供了初步的证据和新的尝试，证实了REMS的这种阶段激活成分是REMS在神经发育中发挥作用的关键过程。我们将剥夺RMS和相关的PGO波，但也会在黑暗中独一无二地唤醒实验中复制的PGO波，以测试替代的PGO波是否能抵消正在进行的RMS剥夺在单眼剥夺动物中引起的LGN细胞大小的变化。RMS状态是控制神经元活动的属性的汇合，可能通过已知的活动依赖突触可塑性机制影响LGN细胞大小。我们的第二组研究是研究特定的谷氨酸受体是否也是REMS的发育效应所必需的，谷氨酸受体是已知的活动依赖发育所必需的。我们通过将谷氨酸受体拮抗剂注入视皮层来验证这一假说，以阻止我们在经历持续视觉不对称的动物中，剥夺REMS对膝状体皮质细胞发育的已证实的和预期的影响。增加我们对与假设的REMS发育功能相关的机制的了解，可能有助于预防和治疗某些睡眠和抑郁病理。表演网站========================================Section End===========================================

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===========================================