Prefrontal Role in Rat Vocalizations and Social Behavior

内侧前额叶皮层（mPFC）在记忆、决策和社会行为中起着重要作用。mPFC直接投射到皮层下结构，产生超声波发声，包括与积极情绪相关的50千赫呼叫和与消极情绪相关的22千赫呼叫。然而，关于如何使用超声波发声以及mPFC在调节它们中起什么作用，仍然知之甚少。我的第一个目标是更多地了解发声是如何在社会互动中使用的。50千赫的叫声可以细分为多达14种不同的叫声类型，我们最近表明，其中许多叫声具有特定的行为相关性。由于无法确定两只相互作用的动物中哪只发出了特定的叫声，这些研究受到了限制。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肌肌电图（EMG）信号。这项技术将应用于幼鼠的嬉戏互动，成年鼠之间潜在的攻击性接触，以及雌雄配对的交配。这将提供一个更清晰的画面，确切地说，发声是如何用来协调社会互动的。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。在猴子身上进行的测绘研究已经确定了扣带皮层中的一个区域，在那里可以通过电刺激引起发声。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发声区域。第二个使用局灶性病变的实验将测试mPFC分区域在发声中的因果作用。总之，这些研究将明确mPFC的哪个区域在调节声音交流中最关键。第三个也是最后一个目的是研究mPFC细胞群中超声波发声的编码。具体来说，大鼠将被植入带有多个电极的微驱动器，允许同时记录行为大鼠的50-100个mPFC细胞。第一项研究将检查单个细胞对录音呼叫（22千赫和各种类型的50千赫呼叫）回放的反应。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)多少比例的mPFC细胞对发声有反应？2)不同的手机会接收不同的电话吗？22千赫和50千赫细胞是混合的还是分离的？总之，本研究提供了超声发声如何用于协调社会互动的更详细的图像，阐明了mPFC的哪些区域参与了发声调节，并提供了mPFC如何代表发声的见解。它的主要影响将是为研究mPFC如何调节社会交流开辟一条全新的途径。

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.