Prefrontal Role in Rat Vocalizations and Social Behavior

内侧前额叶皮质(MPFC)在记忆、决策和社会行为中起着重要作用。MPFC直接投射到皮质下结构，产生超声波发声，其中50 kHz的叫声与积极情绪有关，22 khz的叫声与负面情绪有关。然而，关于超声波发声是如何使用的，以及mPFC在调节它们方面发挥了什么作用，仍有许多未知之处。我的第一个目标是学习更多关于发声是如何在社交中使用的。50 khz的叫声可以细分为多达14种不同的叫声类型，我们最近已经证明，其中许多叫声都有特定的行为关联。由于无法确定两个相互作用的动物中的哪一个发出特定的叫声，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部肌肉肌电(EMG)信号。这项技术将应用于幼年大鼠之间的嬉戏互动，成年大鼠之间潜在的攻击性接触，以及雄性/雌性配对的交配。这将提供一个更清晰的图景，确切地说明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的哪些部分与语音交流最直接相关。对猴子的图谱研究已经确定了扣带回皮质中的一个区域，在那里可以通过电刺激产生发声。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定位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亚区在发声中的因果作用。总而言之，这些研究将明确哪些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标是研究mPFC细胞群中超声波发声的编码。具体地说，大鼠将被植入带有多个电极的微驱动器，允许在行为正常的大鼠的mPFC中同时记录50-100个细胞。第一项研究将考察单个小区对回放录音通话(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细胞中有多少对发声有反应？2)不同的细胞对不同的叫声有反应吗？3)22 khz和50 khz细胞是混合的还是分离的？总之，这项拟议的研究为超声波发声如何用于协调社会互动提供了更详细的图景，阐明了mPFC的哪些区域参与了发声调节，并为mPFC如何代表发声提供了见解。它的主要影响将是为mPFC如何监管社会交流开辟一条全新的研究途径。

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.