Brain size-dependent scaling of dendritic and somatic functions in an evolutionary conserved neuronal circuit in mammals.

在哺乳动物中，大脑和神经元的大小随着头部大小的增加而增大。不可避免地，神经元大小的增加会导致膜电容的增加。为了实现大小无关的突触整合，从而实现功能，神经元的特性，如输入电阻、树突形态、突触电导以及离子通道和突触的数量和位置必须成比例地调节。研究这种伸缩的细胞机制的先决条件是一个进化保守的神经元群体，它独立于头部和大脑的大小完成相同的电路功能。斜方体内侧核(MNTB)神经元满足上述标准，参与双耳加工和上行听觉通路的时频整合。量化MNTB神经元的生物物理和形态细胞参数及其突触输入大小以及通道和突触在不同大小哺乳动物物种中的位置，使我们能够掌握大脑大小依赖神经元缩放的后果。我们的电生理学和免疫荧光发现将在一个计算模型中达到顶峰，以了解单个神经元元件的功能意义。此外，我们可以利用这种比较方法来研究MNTB树突的功能作用，这在很大程度上仍然是未知的。具体地说，通过定量确定树突突触输入对突触潜伏期和动作电位产生的成功的影响，我们可以捕捉到它们在高频输出产生中的潜在作用。

In mammals, brain and neuron size enlarges with increasing head size. Inevitably, an increase in neuron size results in an increased membrane capacitance. To achieve size-independent synaptic integration and, thus, the function, neuronal properties like input resistance, dendritic morphology, synaptic conductance as well as the number and location of ion channels and synapses must scale proportionally. A prerequisite to investigate the cellular mechanisms of such a scaling is an evolutionary conserved neuronal population that fulfills the same circuit function independent of head and brain size. The neurons of the medial nucleus of the trapezoid body (MNTB) fulfill these criteria and are involved in binaural processing and spectro-temporal integration in the ascending auditory pathway. Quantification of the biophysical and morphological cellular parameters of MNTB neurons and their synaptic input size as well as channel and synapse location in differently sized mammalian species, i.e. Etruscan shrew, gerbil and rat, allows us to grasp the consequences of brain size-dependent neuron scaling. Our electrophysiological and immunofluorescence findings will culminate in a computational model to understand the functional significances of individual neuronal elements. Moreover, we can utilize this comparative approach to investigate the functional role of MNTB dendrites, which remains largely unknown. Specifically, by quantitatively determining the influence of dendritic synaptic inputs on synaptic latency and the success of action potential generation, we can capture their potential role in the generation of high frequency outputs.