Optimization of activity-dependent plasticity of cortical circuits: role of neuromodulators, sensory experience, and "arousal"

皮层回路活动依赖性可塑性的优化：神经调节剂的作用、感觉体验和“唤醒”

• 批准号: 203175-2006
• 负责人: Dringenberg, Hans
• 金额: $ 2.39万
• 依托单位: Queen's University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=361517
• 关键词: Optimization; activity; dependent; plasticity; cortical

Brain development is, in part, guided by external, environmental influences. Further, the mature brain also changes in response to external stimuli, a characteristic that allows neurons to encode long-lasting memories. Long-term potentiation (LTP), a relatively stable increase in synaptic strength, is thought to be involved in developmental brain maturation and information encoding in the adult brain. The experiments described here examine mechanisms that mediate the influence of external stimuli and internal (brain) states on brain plasticity (LTP). Three lines of investigation are proposed: 1. How do neuromodulators regulate synaptic plasticity? Levels of many neuromodulators vary with different brain and associated behavioral states (e.g., alertness/attention, active locomotion, stress, sleep). We will identify those neuromodulators (and their mechanisms of action) that play critical roles in the state-dependent regulation of LTP in brain areas known to play an important role in information encoding (hippocampus, neocortex). 2. How does early postnatal sensory (auditory) experience influence the development and plasticity properties of the auditory-receptive area (auditory cortex) of the brain? Lack of "normal" auditory stimulation during postnatal life inhibits the development of the auditory cortex. We will examine the synaptic mechanisms underlying this developmental impairment and will test if it is reversible by appropriate auditory stimulation in adult life. 3. How does emotional "arousal" influence memory encoding and synaptic plasticity (LTP)? It is known that optimal "arousal" levels can facilitate memory encoding. We have observed that rats have an enhanced memory for spatial locations if they encountered a predator stimulus (cat hair) in that location. We will identify brain areas and neurochemicals responsible for mediating this memory-enhancing effect. Together, these studies characterize critical mechanisms that mediate interactions between external stimuli (sensory, predatory), brain and associated behavioral states (brain activation, "arousal"), and the ability of neurons to modify connectivity, an essential process underlying the development and life-long refinement of the central nervous system.

大脑的发育在一定程度上是由外部环境的影响所引导的。此外，成熟的大脑也会对外部刺激做出反应，这是一种允许神经元编码持久记忆的特征。长时程增强（Long-term potentiation，LTP）是一种相对稳定的突触强度增加，被认为与发育中的大脑成熟和成年大脑的信息编码有关。这里描述的实验研究了外部刺激和内部（大脑）状态对大脑可塑性（LTP）的影响的调节机制。提出了三条调查路线：1。神经调质如何调节突触可塑性？许多神经调质的水平随着不同的大脑和相关的行为状态而变化（例如，警觉性/注意力、主动运动、压力、睡眠）。我们将确定那些在已知在信息编码中起重要作用的大脑区域（海马体，新皮层）的LTP状态依赖性调节中发挥关键作用的神经调质（及其作用机制）。2.出生后早期的感觉（听觉）经验如何影响大脑听觉-感受区（听觉皮层）的发育和可塑性？出生后缺乏“正常”的听觉刺激会抑制听觉皮层的发育。我们将研究这种发育障碍背后的突触机制，并测试成年后适当的听觉刺激是否可以逆转。3.情绪“唤醒”如何影响记忆编码和突触可塑性（LTP）？众所周知，最佳的“唤醒”水平可以促进记忆编码。我们已经观察到，如果大鼠在该位置遇到捕食者刺激（猫毛），它们对空间位置的记忆会增强。我们将确定负责介导这种记忆增强效应的大脑区域和神经化学物质。总之，这些研究表征了介导外部刺激（感觉，捕食），大脑和相关行为状态（大脑激活，“唤醒”）之间相互作用的关键机制，以及神经元修改连接的能力，这是中枢神经系统发育和终身完善的基本过程。