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直接投射到产生超声波发声的皮层下结构，50 kHz的声音与积极情绪有关，22 kHz的声音与消极情绪有关。 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，还有很多未知之处。 我的第一个目标是更多地了解发声在社会交往中是如何使用的。 50 kHz的电话可以细分为多达14个不同的呼叫类型，我们最近已经表明，许多这些电话有特定的行为相关。 这些研究受到了限制，因为无法确定两种相互作用的动物中哪一种发出了特定的叫声。 因此，我建议记录发声，同时记录喉肌肉肌电图（EMG）信号使用植入的无线发射器。 该技术将应用于幼年大鼠的嬉戏互动，成年大鼠之间的潜在攻击性遭遇，以及雄性/雌性对的交配。 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。 我的第二个目标是确定mPFC的哪些部分最直接参与语音交流。 对猴子的绘图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扣带回发声区。 第二个实验使用局灶性病变将测试的因果关系的mPFC子区域在发声的作用。这些研究将共同澄清哪些mPFC区域在调节声音交流方面最关键。 第三个也是最后一个目的是研究mPFC细胞系中超声发声的编码。 具体而言，大鼠将被植入具有多个电极的微驱动器，允许同时记录行为大鼠mPFC中的50-100个细胞。 第一项研究将检查单个细胞对回放记录的呼叫（22 kHz和各种类型的50 kHz呼叫）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)不同的细胞是否被调谐到不同的呼叫？ （3）22 kHz和50 kHz细胞是否混杂或分离？总之，拟议的研究提供了一个更详细的图片如何超声波发声用于协调社会互动，阐明哪些区域的mPFC参与发声调节，并提供见解如何mPFC代表发声。 它的主要影响将是开辟一条全新的研究途径，研究mPFC如何调节社会沟通。

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.