Local circuit and projection based prefrontal response diversity for action control in rats

关于何时采取行动的决定取决于外部和内部因素。外部因素与来自环境的线索有关，而内部因素与一系列不同的先前经历和由此产生的动机或身体状态有关。受试者必须综合这些因素，并相应地灵活调整自己的行为，才能最大限度地提高成功率。这些决定部分是在前额叶皮质(PFC)做出的，必须转化为运动皮质区域的行动计划，该区域直接向脊髓发送输出信号。有几条通路是从PFC到运动皮质区域的信息传递的候选通路。在这个项目中，我们将重点放在前额-丘脑的投射，区分投射到内侧背侧核和丘脑腹内侧核(MD和Vm)。我们的目标是确定从中间PFC(MPFC)通过这两条路径发出的信息质量是否存在差异，以及这与mPFC中任务依赖和输出依赖的集合的灵活形成有何关系。为此，我们将在大鼠的运动准备/抑制任务期间，在mPFC的前部(PL)以及MD和Vm进行电生理记录。在这项任务中，老鼠必须用杠杆释放来对听觉信号做出反应。通过改变所需的等待时间和奖励方案，我们将探索哪些参数对于老鼠决定何时释放是必不可少的。这将通过强化学习方法进行建模，以确定大鼠的行为规则以及与神经元反应和通路相关的因素。为了阐明电路特异性效应，我们将通过阻断PL-MD或PL-VM通路来选择性地操纵两种结构之间的通路。这些数据将被输入到递归神经网络(RNN)模型中，以揭示神经元活动规律，从而缩小神经元反应的复杂性，并有助于解释mPFC的神经元灵活性。根据核心假设1，我们将研究时间协调模式(即振荡爆发)如何以决策和状态依赖的方式动态组织任务中的前额叶集合。我们假设神经元活动可以被识别为由时间组织的尖峰活动定义的神经元集合。与核心假设2一致，我们假设这些前额叶集合至少部分是通过输出到MD和Vm来定义的。

Decisions about when to act are depend on external and internal factors. External factors relate to cues from the environment, while internal factors relate to a diverse set of previous experiences and resulting motivational or physical states. Subjects have to integrate these factors and flexibly adapt their behavior accordingly in order to maximize their success rate. These decisions are partially made in the prefrontal cortex (PFC) and have to be translated into action plans in motor cortical areas which directly send output signals to the spinal cord. Several pathways are candidates for the information transfer from PFC to motor cortical areas. In this project, we will focus on prefrontal-thalamic projections with a differentiation between the projections to the mediodorsal and the ventromedial thalamic nucleus (MD and VM). We aim to define whether there is a distinction between the information quality which is sent out from the medial PFC (mPFC) via these two routes and how this relates to the flexible formation of task-dependent and output-dependent ensembles in mPFC. For this we will conduct electrophysiological recordings in the prelimbic (PL) portion of the mPFC, and in the MD and VM during a motor preparation/inhibition task in rats. In this task, rats have to respond to an auditory signal with a lever release. By varying the required holding time and the reward scheme, we will probe which parameters are essential for the rats’ decision when to release. This will be modelled via a reinforcement learning approach to identify the rules according to which the rats act and which factors relate to neuronal responses and pathways. In order to elucidate circuit specific effects, we will selectively manipulate the pathways between the two structures by either blocking the PL-MD or PL-VM pathway. The data will be fed into a recurrent neural network (RNN) model to reveal neuronal activity rules which narrow down the complexity of neuronal responses and help explaining the neuronal flexibility of the mPFC. In line with the core hypothesis 1, we will investigate how patterns of temporal coordination (i.e. oscillatory bursts) dynamically organize prefrontal ensembles across the task in a decision and state dependent manner. We hypothesize that neuronal activity can be identified as neuronal ensembles defined by temporally organized spiking activity. In line with core hypothesis 2, we hypothesize that these prefrontal ensembles are at least partially defined through outputs to MD and VM.