Synaptic basis for map plasticity in cerebral cortex

感官体验有力地调节着大脑皮层中大脑回路的发育， 有助于皮质发育的后期阶段，也有助于成人学习。蜂窝 使经验能够改变皮层回路的机制尚未被理解。这些 机制可以在大脑皮层的感觉区进行研究，这些感觉区包含有序的感觉地图 其地形被最近的感官体验模式所改变。地图的标准模型 可塑性假设可塑性的快速成分反映了长时程突触增强（LTP）， 抑郁症（LTD），由N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体介导，在特定的 皮层兴奋性突触支持这一模型，最近的研究已经直接检测到LTP， 感觉经验在皮层突触诱发LTD。然而，新的数据表明，LTD在 许多皮层突触并不通过经典的NMDA依赖性机制来运作，而是 涉及通过大麻素1型（CB 1）受体的逆行信号传导。细胞信号传导 皮质中CB 1依赖性LTD的途径尚不清楚。我们建议澄清这些 机制，并了解CB 1-LTD如何实现皮质的Hebbian符合检测 可塑性。以啮齿动物躯体感觉皮层的须区为模型系统。我们将 还测试了CB 1受体是否在发育和可塑性中发挥了意想不到的因果作用。 大脑皮层回路，正如这些发现所表明的那样。 在另一个进展中，最近的研究表明，感官体验不仅调节兴奋性， 突触，还有抑制回路。抑制回路可塑性的流行及其具体作用 在皮层回路发育和可塑性方面的作用尚不清楚。我们建议确定特定的抑制性 神经元和电路，由感官经验调节，并表征细胞 这种可塑性的机制我们将具体探讨抑制性神经元的可塑性 回路在标测过程中发挥稳态作用，以维持兴奋和抑制之间的平衡 可塑性。总之，这些实验将扩展目前的经验依赖性皮层模型， 发展超越NMDA依赖性LTP和LTD，包括大麻素依赖性 机制和抑制回路。研究结果可能为可塑性相关疾病提供新的治疗策略。 神经系统疾病，包括精神发育迟缓、自闭症和学习障碍。 皮质发育中大麻素信号通路的参与也可能具有重要的 对儿童和胎儿发育期间滥用大麻素的影响。

Sensory experience powerfully regulates development of brain circuits in the cerebral cortex, contributing to late stages of cortical development, and also to adult learning. The cellular mechanisms that enable experience to alter cortical circuits are not yet understood. These mechanisms can be studied in sensory areas of cerebral cortex, which contain orderly sensory maps whose topography is altered by recent patterns of sensory experience. The standard model for map plasticity posits that rapid components of 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. Supporting this model, recent studies have directly detected LTP and LTD induced at cortical synapses by sensory experience. However, new data suggest that LTD at many cortical synapses does not operate by classical, NMDA-dependent mechanisms, but instead involves retrograde signaling via the cannabinoid type 1 (CB1) receptors. The cellular signaling pathways for CB1-dependent LTD in cortex are not understood. We propose to elucidate these mechanisms, and to understand how CB1-LTD implements Hebbian coincidence detection for cortical plasticity. The whisker region of rodent somatosensory cortex is used as a model system. We will also test whether CB1 receptors play an unexpected causal role in development and plasticity of cortical circuits, as these findings suggest. In another advance, recent studies indicate that sensory experience regulates not only excitatory synapses, but also inhibitory circuits. The prevalence of inhibitory circuit plasticity, and its specific role in cortical circuit development and plasticity, is not known. We propose to identify specific inhibitory neurons and circuits that are regulated by sensory experience, and to characterize the cellular mechanisms for this plasticity. We will specifically explore the hypothesis that plasticity of inhibitory circuits acts homeostatically to maintain the balance between excitation and inhibition during map plasticity. Together, these experiments will expand current models of experience-dependent cortical development beyond NMDA-dependent LTP and LTD, to include cannabinoid-dependent mechanisms and inhibitory circuits. Results may suggest novel therapeutic strategies for plasticityrelated 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.