DEVELOPMENT OF THALAMOCORTICAL SYNAPTIC INPUTS

丘脑皮质突触是所有感觉的唯一通道 进入大脑皮层的信息。因此，它是一个至关重要的关键 从感觉到感官知觉的路径，以及它 正常发育是获得成熟的必要前提 皮质功能。一种独特的体外制剂，其中 保留丘脑皮质通路，并利用功能性 结合全细胞记录、细胞内染色、轴突 示踪和共聚焦成像，以研究形态、药理和 从丘脑皮质突触的发生看其生理发育 在新生儿早期至成熟期。拟议的研究将审查 突触特性的详细变化，特别是 强调NMDA受体介导的成分，它被认为具有 具有适应环境影响的能力的系统。完整的- 来自大脑皮层细胞的细胞记录将解决几个特定的 问题：(1)丘脑皮质对深层细胞的输入 (第V/VI层)形成于早期的非特异性和旺盛时期 新生儿期，和“不适当”的连接后来收回？(2)做 深层细胞接受它们的大部分突触输入是在其 基础树突，来自深层丘脑皮质终末，或在 它们的顶端树突，来自第四层丘脑皮质终末？(3)是 NMDA与NMDA的相对贡献在发育过程中呈下降趋势 非NMDA受体介导的突触电流，在激活时间 N-甲基-D-天冬氨酸受体介导的电流，无论是在镁敏感性还是在其病例中 渗透性，这可能是成熟期失去可塑性的原因 动物？来自突触耦合的双同时录音 丘脑皮质投射细胞和皮质IV层细胞将处理 单轴突水平丘脑皮质突触功能的发育 并将检查丘脑皮质突触的综合特性。 数量分析方法将揭示人类的发育增长是否 末端乔木的复杂性伴随着更多的分歧或 统一反应的大小增加，以及后者是否 加压起源于突触后或突触前。

The thalamocortical synapse is the sole gateway for all sensory information entering the neocortex. It is therefore a crucial linchpin in the pathways that lead from sensation to sensory perception, and its normal development is a necessary prerequisite for acquisition of mature cortiCal function. A unique in vitro preparation in which the thalamocortical pathway is retained and functional will be utilized in conjunction with whole-cell recordings, intracellular staining, axonal tracing and confocal imaging, to study morphological, pharmacological and physiological development of thalamocortical synapses from their genesis in the early neonatal period to maturity. The proposed study will examine in detail changes in the properties of the synapse, with particular emphasis on the NMDA receptor-mediated component which is thought to endow the system with the capacity to adjust to environmental influences. Whole- cell recordings from cortical cells will address several specific questions: (1) Are thalamocortical inputs to cells in the deep layers (layers V/VI) formed non-specifically and in exuberance in the early neonatal period, and "inappropriate" connections later retracted? (2) Do deep layer cells receive the majority of their synaptic inputs on their basal dendrites, from thalamocortical terminals in the deep layers, or on their apical dendrites, from thalamocortical terminals in layer IV? (3) Is there a developmental reduction in the relative contribution of NMDA vs non-NMDA receptor-mediated synaptic currents, in the activation time of the NMDA receptor-mediated current, in its Mg sensitivity or in its Ca permeability, which could account for loss of plasticity in the mature animal? Dual simultaneous recordings from synaptically coupled thalamocortical projection cells and cortical layer IV cells will address development of thalamocortical synaptic function at the single axon level and will examine integrative properties of the thalamocortical synapse. Quantal analysis methods will reveal whether the developmental increase in terminal arbor complexity is accompanied with increased divergence or with an increase in the size of the unitary response, and whether the latter increase is post- or presynaptic in origin.