视前核控制母性行为的分子及神经环路机制

Explaining how brain controls complex behaviors is one of the central questions in neuroscience research. Maternal behaviors are innate behaviors that are displayed reliably in many species in the nature. Because maternal behaviors are evolutionarily conserved, easily quantifiable and are subjected to genetic manipulation, they make an ideal model for studying how the brain encodes complex behaviors. Previous studies have implicated the preoptic nucleus as an essential brain site for regulating maternal behaviours. However, little is known about the exact neuronal types involved in such regulation, or the neural circuits that they participate in, or the genetic basis of their function. We hypothesize that different neurons within the preoptic nucleus play distinct roles in regulating retrieval, nursing or nest building behaviors within the maternal behavioral repertoire. To test this hypothesis, we will utilize cutting edge molecular genetic manipulations, optogenetic and neural circuit mapping techniques to dissect the function of different preoptic neurons from gene, cell and neural circuit level. This research will not only open a new chapter in the study of maternal behaviors and answer systematically how the brain controls maternal behaviors, it will also provide experimental supports to reveal fundamental design principles of how brain controls complex behaviors. Thus, this proposal is of great scientific merits and significance.

大脑如何编码和支配行为是神经科学的中心问题之一。母性行为是一种在自然界中广泛存在的本能行为。由于母性行为具有稳定性、进化保守性、可量化性及可遗传操纵性，因此是揭示大脑编码和支配复杂行为神经机制的理想模型。以往的实验暗示内侧视前核是控制母性行为的重要脑区，但是人们对于参与行为调控的具体神经元类型、神经环路基础以及分子机制仍然知之甚少。我们推测内侧视前核内不同类型神经元及其到特异脑区的投射在寻觅、哺育和做窝等多种母性行为中起不同的调控作用。我们将利用最先进的分子遗传学操作、光遗传学及环路追踪的手段，从基因、神经元以及神经环路多个层次来验证这一推测。此项研究不仅将开创母性行为研究的新篇章，系统阐述大脑支配母性行为的神经机制，而且将为揭示大脑控制复杂行为的基本原则提供实验依据，因此具有重要的研究意义。

本能行为关系到个体生存和种族繁衍。本项目以下丘脑内侧视前核为切入点，系统研究了本能母性行为的神经基础。我们发现，内侧视前区不同类型的神经元介导母性中不同的关爱行为，其中，Vgat+ or Esr1+ 神经元介导叼幼崽行为，而Vgat+/Esr1-神经元在筑巢行为中起重要作用。同时我们还发现在雄鼠中人为激活内侧视前核也可以诱导出母性行为的发生，首次证明雄鼠脑中也具有支配母性行为的神经环路。在此基础上，我们发现掌管摄食的Agrp神经元特异性的投射到视前区Vgat+ 神经元上，通过抑制这些神经元来抑制母性筑巢行为，从而介导饥饿状态下的行为选择。因此，我们的研究揭示了母性行为的神经基础以及行为抉择的神经环路机制。