Synaptic basis for map plasticity in cerebral cortex

大脑皮层图谱可塑性的突触基础

• 批准号: 7917978
• 负责人: Daniel Feldman
• 金额: $ 39.82万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7917978
• 关键词: Age; Area; Autistic Disorder; Brain; Calcium Channel; Cannabinoids; Cells; Cerebral cortex; Chemosensitization; Child; Detection; Development; Endocannabinoids; Equilibrium; Excitatory Synapse; Fetal Development; Glutamate Receptor; In Vitro; Inhibitory Synapse; Interneurons; Knockout Mice; Learning Disabilities; Long-Term Potentiation; Maps; Measures; Mediating; Mental Depression; Mental Retardation; Modeling; Molecular; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; Neocortex; Neurodevelopmental Disorder; Neurons; Pharmacology; Play; Prevalence; Process; Pyramidal Cells; Research; Rodent; Role; Sensory; Signal Pathway; Signal Transduction; Somatosensory Cortex; Staging; Synapses; Synaptic plasticity; System; Testing; Vibrissae; Work; base; cannabinoid receptor; critical period; deprivation; detector; experience; hippocampal pyramidal neuron; in vivo; nervous system disorder; novel; novel therapeutics; postsynaptic; presynaptic; prevent; receptor; research study; somatosensory; voltage

Sensory experience powerfully regulates the development of circuits in the cerebral cortex, contributing to late stages of cortical development. The cellular mechanisms by which experience alters cortical circuits are not yet understood. This process can be studied in sensory areas of cerebral cortex, which contain orderly sensory maps whose topography is altered by sensory experience. The standard model posits that rapid components of map plasticity reflect long-term synaptic potentiation (LTP) and depression (LTD), mediated by N-methyl-D-aspartate (NMDA)-type glutamate receptors, at specific cortical excitatory synapses. Recent evidence has supported this model by directly detecting LTP and LTD induced at cortical synapses by sensory experience. However, new findings suggest that during early critical periods, LTD at many cortical synapses does not operate by classical, NMDA-dependent mechanisms, but instead involves retrograde signaling via the newly discovered endocannabinoid system and cannabinoid (CB) receptors. The cellular signaling pathways for CB-dependent LTD in cortex are not understood. We propose to elucidate these mechanisms in the whisker region of rodent somatosensory cortex. We will also test whether, as these findings suggest, CB receptors play an unexpected causal role in development and plasticity of cortical circuits. These experiments will expand current models of experience-dependent cortical development beyond NMDA-dependent LTP and LTD, to include cannabinoid-dependent mechanisms. Results may suggest novel therapeutic strategies for plasticity-related neurological disorders, including mental retardation, autism, and learning disability. Involvement of cannabinoid signaling pathways in cortical development may also have major implications for cannabinoid abuse in children and during fetal development.

感官体验有力地调节大脑皮层回路的发育，有助于皮层发育的后期阶段。经验改变皮质回路的细胞机制尚不清楚。这个过程可以在大脑皮层的感觉区域进行研究，该区域包含有序的感觉图，其地形会因感觉体验而改变。标准模型认为，图谱可塑性的快速成分反映了特定皮质兴奋性突触处由 N-甲基-D-天冬氨酸 (NMDA) 型谷氨酸受体介导的长期突触增强 (LTP) 和抑制 (LTD)。最近的证据通过直接检测感觉经验在皮层突触诱发的 LTP 和 LTD 支持了该模型。然而，新的研究结果表明，在早期关键时期，许多皮质突触的 LTD 并不是通过经典的、NMDA 依赖性机制运作的，而是通过新发现的内源性大麻素系统和大麻素 (CB) 受体涉及逆行信号传导。皮质中 CB 依赖性 LTD 的细胞信号传导途径尚不清楚。我们建议阐明啮齿动物体感皮层胡须区域的这些机制。我们还将测试 CB 受体是否如这些研究结果所表明的那样，在皮质回路的发育和可塑性中发挥着意想不到的因果作用。 这些实验将扩展当前经验依赖性皮层发育模型，超越 NMDA 依赖性 LTP 和 LTD，以包括大麻素依赖性机制。研究结果可能为可塑性相关的神经系统疾病（包括智力低下、自闭症和学习障碍）提出新的治疗策略。大麻素信号通路参与皮质发育也可能对儿童和胎儿发育期间的大麻素滥用产生重大影响。

项目成果

Synaptic mechanisms for plasticity in neocortex.

• DOI: 10.1146/annurev.neuro.051508.135516
• 发表时间: 2009
• 期刊: Annual review of neuroscience
• 影响因子: 13.9
• 作者: Feldman DE

Development of columnar topography in the excitatory layer 4 to layer 2/3 projection in rat barrel cortex.

大鼠桶状皮层兴奋性层 4 至层 2/3 投影中柱状地形的发展。

• DOI: 10.1523/jneurosci.23-25-08759.2003
• 发表时间: 2003
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Bender,KevinJ;Rangel,Juliana;Feldman,DanielE
• 通讯作者: Feldman,DanielE

Presynaptic NMDA receptors: newly appreciated roles in cortical synaptic function and plasticity.

• DOI: 10.1177/1073858408322675
• 发表时间: 2008-12
• 期刊: The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
• 作者: Corlew R;Brasier DJ;Feldman DE;Philpot BD
• 通讯作者: Philpot BD