Prefrontal Role in Rat Vocalizations and Social Behavior

前额叶在大鼠发声和社会行为中的作用

• 批准号: RGPIN-2018-05777
• 负责人: Euston, David
• 金额: $ 2.11万
• 依托单位: University of Lethbridge
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761409
• 关键词: Prefrontal; Role; Rat; Vocalizations; Social

The medial prefrontal cortex (mPFC) plays important roles in memory, decision making, and social behaviour. The mPFC projects directly to subcortical structures that generate ultrasonic vocalizations, both the 50 kHz calls associated with positive affect and the 22 kHz calls associated with negative affect. However, much remains unknown about how ultrasonic vocalizations are used and what role the mPFC plays in regulating them. My first aim is to learn more about how vocalizations are used in social interactions. The 50 kHz calls can be subdivided into as many as 14 distinct call types and we have recently shown that many of these calls have specific behavioural correlates. These studies have been limited by the inability to determine which of two interacting animals is giving a particular call. Hence, I propose to record vocalizations while simultaneously recording larynx muscle electromyographic (EMG) signals using an implanted wireless transmitter. This technique will be applied to playful interactions in juvenile rats, potentially aggressive encounters among adult rats, and mating in male/female pairs. This will provide a much clearer picture of exactly how vocalizations are used to coordinate social interactions. My second aim is to determine which parts of mPFC are most directly involved in vocal communication. Mapping studies in monkeys have identified a region in the cingulate cortex where vocalizations can be elicited by electrical stimulation. Do rats have a similar region? To answer this question, I propose to use electrode arrays to map the cingulate vocalization region in rats. A second experiment using focal lesions will test the causal role of mPFC subregions in vocalizations. Together, these studies will clarify exactly which mPFC regions are most critical in regulating vocal communication. A third and final aim is to examine the encoding of ultrasonic vocalizations in ensembles of mPFC cells. Specifically, rats will be implanted with microdrives with multiple electrodes, allowing for the simultaneous recording of 50-100 cells in mPFC in behaving rats. A first study will examine the responses of single cells to the playback of recorded calls (22 kHz and the various types of 50 kHz calls). A second experiment will examine neural responses during the production of vocalizations. These experiments will address question such as: 1) What fraction of mPFC cells are responsive to vocalizations? 2) Are different cells tuned to different calls? and 3) Are 22 kHz and 50 kHz cells intermingled or segregated? In sum, the proposed research with provide a much more detailed picture of how ultrasonic vocalizations are used to coordinate social interactions, elucidate which regions of mPFC are involved in vocal regulation, and provide insights into how the mPFC represents vocalizations. Its primary impact will be to open an entirely new avenue of research into how mPFC regulates social communication.

内侧前额叶皮层 (mPFC) 在记忆、决策和社会行为中发挥着重要作用。 mPFC 直接投射到产生超声波发声的皮层下结构，包括与积极情绪相关的 50 kHz 呼叫和与消极情绪相关的 22 kHz 呼叫。 然而，关于超声波发声的使用方式以及 mPFC 在调节超声波发声方面发挥的作用，目前仍有很多未知之处。 我的第一个目标是更多地了解如何在社交互动中使用发声。 50 kHz 呼叫可以细分为多达 14 种不同的呼叫类型，我们最近表明，其中许多呼叫都具有特定的行为相关性。 这些研究受到限制，因为无法确定两只相互作用的动物中哪一只正在发出特定的叫声。 因此，我建议在记录发声的同时，使用植入的无线发射器记录喉部肌肉肌电图 (EMG) 信号。 该技术将应用于幼年大鼠的嬉戏互动、成年大鼠之间潜在的攻击性遭遇以及雄性/雌性配对的交配。 这将更清楚地说明如何使用发声来协调社交互动。 我的第二个目标是确定 mPFC 的哪些部分最直接参与声音交流。 对猴子进行的绘图研究发现，扣带皮层中有一个区域可以通过电刺激引发发声。 老鼠也有类似的区域吗？ 为了回答这个问题，我建议使用电极阵列来绘制大鼠的扣带回发声区域。 使用局灶性病变的第二个实验将测试 mPFC 子区域在发声中的因果作用。这些研究将共同​​阐明哪些 mPFC 区域在调节声音交流中最关键。 第三个也是最后一个目标是检查 mPFC 细胞群中超声波发声的编码。 具体来说，老鼠将被植入带有多个电极的微驱动器，从而可以同时记录行为老鼠 mPFC 中的 50-100 个细胞。 第一项研究将检查单个细胞对回放录音通话（22 kHz 和各种类型的 50 kHz 通话）的反应。 第二个实验将检查发声过程中的神经反应。这些实验将解决以下问题：1）mPFC 细胞的哪一部分对发声有反应？ 2) 不同的小区是否调谐到不同的呼叫？ 3) 22 kHz 和 50 kHz 单元是混合还是分离？总之，拟议的研究提供了如何使用超声波发声来协调社交互动的更详细图片，阐明了 mPFC 的哪些区域参与发声调节，并提供了有关 mPFC 如何代表发声的见解。 其主要影响将是为 mPFC 如何调节社交沟通开辟一条全新的研究途径。