Area-specific differences in cortical presynaptic coupling distances

大脑中的信息处理依赖于突触传递和可塑性。动作电位打开突触前活动区的钙通道。流入的钙通过与囊泡释放传感器蛋白结合而触发突触囊泡的融合。然而，钙浓度随着与通道距离的增加而迅速降低。这使得通道和囊泡之间的空间耦合距离成为突触传递的保真度和可塑性的关键决定因素。迄今为止，已经区分了两种主要的耦合配置：紧密的纳米畴耦合和松散的微畴耦合。在成熟的大脑中，紧密耦合被发现在不同的兴奋性突触与高的传输保真度，特别是突触传输频率编码的感觉信息或经常性的兴奋。在这些突触中，紧密耦合在出生后成熟时从松散耦合发展而来。另一方面，在成熟的大脑中，在海马体中高度可塑的兴奋性突触处发现了松散耦合。然而，这是否构成一般规则目前尚不清楚。特别是，目前还不清楚是否耦合距离和地形不同，在相同的主要类型的突触，如果他们从事不同的功能。新皮层或等皮层是一个形态上同质的大脑区域，涵盖了高度多样化的功能，从早期的感觉处理和运动控制到高阶联想和认知功能。值得注意的是，所有这些不同的功能都是由相同的神经元和突触原型执行的，尽管它们位于新皮层的不同区域。在这里，提出的假设是，在成熟的新皮层的特定区域的功能差异相关联的，甚至产生于相同的主要类型的突触的功能突触前纳米架构的差异，如果它们位于不同的皮层区域。具体来说，我建议，在从事低阶处理（如初级躯体感觉皮层）的皮质区的第2/3和第5层的主要锥体神经元之间的突触与紧密的纳米结构域耦合，这种紧密的耦合在出生后的成熟过程中发展。另一方面，我认为，相同的主要类型的突触，即使在成熟的皮层中，如果它们位于从事高阶处理的区域（如前额叶皮层），也会以松散的微区耦合进行操作。突触纳米形貌的这些差异将引起传递保真度和可塑性的特征差异。提案中的初步数据支持这一假设。我建议，在特定的新皮层区域和层的相同的原型突触之间的耦合距离的发展动力学的比较将产生重要的新的见解突触前的结构-功能的关系，并最终甚至可能允许推导出这些关系的一般规则。

Information processing in the brain relies on synaptic transmission and plasticity. An action potential opens calcium channels at the presynaptic active zone. Inflowing calcium triggers the fusion of synaptic vesicles by binding to a vesicular release sensor protein. Yet, the calcium concentration rapidly decreases with increasing distance from the channel. This makes the spatial coupling distance between channels and vesicles a key determinant of the fidelity and plasticity of synaptic transmission. Two principle coupling configurations have been distinguished to date: tight nanodomain coupling and loose microdomain coupling. In the mature brain, tight coupling was found at different excitatory synapses with high transmission fidelity, in particular synapses transmitting frequency-coded sensory information or recurrent excitation. At these synapses, tight coupling developed from loose coupling during postnatal maturation. Loose coupling, on the other hand, was found in the mature brain at a highly plastic excitatory synapse in the hippocampus. However, whether this constitutes a general rule is currently unclear. In particular, it is unclear whether coupling distances and topographies differ at the same principal types of synapses if they are engaged in different functions. The neo- or isocortex is a morphologically homogeneous brain region that covers highly diverse functions, ranging from early sensory processing and motor control up to higher order associations and cognitive functions. Notably, all of these different functions are performed by the same archetypes of neurons and synapses albeit in different areas of the neocortex. Here, the hypothesis is put forth that area-specific functional differences in the mature neocortex are associated with or even arise from differences in the functional presynaptic nanoarchitecture of the same principal types of synapses if they are located in different cortical areas. Specifically, I propose that synapses between the principal pyramidal neurons in layers 2/3 and 5 in cortical areas engaged in lower order processing (e.g. primary somatosensory cortex) operate with tight nanodomain coupling and that this tight coupling develops during postnatal maturation. On the other hand, I propose that the same principal types of synapses operate with loose microdomain coupling even in the mature cortex if they are located in areas engaged in higher order processing (e.g. prefrontal cortex). These differences in the synaptic nanotopographies will give rise to characteristic differences in transfer fidelity and plasticity. Preliminary data in the proposal supports this hypothesis. I propose that a comparison of the developmental dynamics of coupling distances between the same archetypes of synapses in specific neocortical areas and layers will yield important novel insights into the presynaptic structure – function relationships and may ultimately even allow for deducing a general rule for these relationships.