Molecular, spatial, and functional development of innate behavior in the periaqueductal gray

项目摘要 大脑通过不同类型细胞的协同行动来产生行为。最近的研究在基因上 已识别的控制特定本能行为的细胞类型，例如在 内侧视前区(MPOA)，这是父母养育子女所必需的，或表达AgRP和POMC的神经元 弓状核，它们对进食至关重要。然而，对细胞如何以及何时发生还没有很好的了解 对本能行为重要的类型是在出生后发育过程中定义的。 中脑导水管周围灰质(PAG)被认为是许多前脑信号的整合区域。它收到了主要的 来自下丘脑、杏仁核和前额叶皮质的传入信息，并将适当的信号传递到 脑干和脊髓。虽然PAG对于出生时存在的特定功能是必需的，例如 发声和哺乳，PAG的其他功能，包括交配和攻击，直到 在以后的生活中。这导致了一种假设，即控制这些行为所需的细胞类型还不成熟 直到晚年。这项提议的目标是发现细胞如何以及何时获得成熟的功能 在PAG中的意义。这项提案的发现将提供对PAG相关行为的洞察 病理及其可能产生的原因，例如慢性焦虑和过度攻击性。 目标1将利用单核RNA来定义PAG细胞类型及其出生后的发育轨迹。 小鼠在P1、P7、P14、P28和P50-P60(成人)的测序。目标2将在空间上定义发展 并使用多重错误稳健荧光原位杂交技术检测PAG中细胞类型的分布。目标 3将确定在年龄相关的先天行为中活跃的PAG细胞类型(P1/P7，发声；P14，恐惧；P28， 攻击性、成年期、交配和育儿)使用一组20个直接早期基因作为最近的 细胞活动。 初步数据显示，随着年龄的增长，细胞表达的基因总数会增加。使用数据 根据不同年龄的计算，几个星系团的初步发展轨迹显示了年龄- 与感受性和信号有关的基因的依赖性增加，如神经肽及其受体。 这支持了这样的假设，即随着年龄的增长，细胞通过基因上调获得新的功能能力 这就增加了蜂窝串扰。本提案旨在定义这些职能，并具体确定 哪些基因与这一功能上调相一致。

Project Summary The brain generates behavior through the concerted action of diverse cell types. Recent work has genetically identified cell types governing specific instinctive behaviors, such as neurons expressing galanin within the medial preoptic area (MPOA), which are are necessary for parenting, or Agrp and POMC-expressing neurons of the arcuate nucleus, which are critical for feeding. However, it is not well understood how and when cell types important to instinctive behaviors are defined during postnatal development. The periaqueductal gray (PAG) is thought to serve as an integrator of many forebrain signals. It receives major input from the hypothalamus, amygdala, and prefrontal cortex, and transmit proper signals to motor nuclei of the brainstem and spinal cord. While the PAG is necessary for specific functions present at birth, such as vocalization and suckling, other functions of the PAG, including mating and aggression are not manifested until later in life. This leads to the hypothesis that cell types necessary to control these behaviors are not mature until later in life. The goal of this proposal is to discover how and when cells gain their mature functional significance in the PAG. The findings from this proposal will provide insight about PAG-related behavioral pathologies and how they may arise, for example chronic anxiety and excessive aggression. Aim 1 will define PAG cell types and their postnatal developmental trajectories utilizing single nucleus RNA- sequencing from mice at P1, P7, P14, P28, and P50-P60 (adult). Aim 2 will spatially define the development and distribution of cell types in the PAG using Multiplexed Error Robust Fluorescent In Situ Hybridization. Aim 3 will determine PAG cell types active in age-dependent innate behaviors (P1/P7, vocalization; P14, fear; P28, aggression; adult, mating and parenting) using a panel of 20 immediate early genes as a readout of recent cellular activity. Preliminary data shows that cells increase the overall number of genes expressed with age. Using data computationally aligned across ages, preliminary developmental trajectories of several clusters show age- dependent increases in genes relevant for receptivity and signaling, such as neuropeptides and their receptors. This supports the hypothesis that with age, cells gain new functional capacities through upregulation of genes that allow for increased cellular crosstalk. This proposal seeks to define these functions and specifically identify which genes are upregulated concordantly with that function.