SSA: Cholinergic modulation of spatial memory in cortical brain circuits (Ref: 3981)

学习和记忆是最基本的心理过程之一，因为它们允许我们利用经验来解决问题和调整我们的行为。乙酰胆碱(ACh)是一种神经调节剂，被认为是学习和记忆的重要调节因子。该项目将结合各种体内和体外技术和计算分析，以破译ACh如何调节大脑新皮质的学习和记忆处理。脾后皮质(RSC)是新皮质的一个区域，是大脑回路中的一个关键节点，对学习和记忆至关重要。特别是，RSC对于区分不同地方的记忆是很重要的，这是一种被回忆的空间记忆。RSC有丰富的胆碱能(即ACh释放)突触供应，表明ACh在RSC的空间记忆加工中起重要作用。我们有很好的证据表明ACh可以重新配置RSC中的神经活动，但目前几乎不知道ACh是如何或何时调节RSC中空间记忆的处理。本项目的具体目的是(I)确定ACh调节RSC中神经元之间的通讯的细胞和突触机制，以及(Ii)确定ACh如何调节RSC中空间记忆的处理。为了实现这些目标，你将加入一个充满活力的研究社区，这个社区横跨英国两所领先的研究型大学埃克塞特和布里斯托尔，与一个由6名博士后和10名博士后组成的团队一起工作，他们分别在埃克塞特的JonWitton博士、布里斯托尔的Jack Mellor教授和埃克塞特的乔恩·布朗博士的实验室工作。你将接受尖端的体外和体内技术培训，使用小鼠遗传学、膜片钳电生理学、光遗传学和药理学来解决AIM(I)，并使用体内脑成像和行为分析来解决AIM(Ii)。你还将通过编写新的分析算法来发展计算机编程技能。这个项目将为理解ACh如何调节大脑皮质回路中学习和记忆的处理奠定新的基础。这将有助于我们更好地了解ACh信号中断是如何导致阿尔茨海默氏症等神经系统疾病的学习和记忆丧失的，以及目前的ACh促进药物(例如多奈哌齐)实际上是如何增强患者的认知能力的。总而言之，这是一个高度跨学科的项目，在一个令人兴奋和重要的神经科学研究领域提供了一个特殊的培训机会。

Learning and memory are amongst the most fundamental mental processes, as they allow us to use experience tosolve problems and adapt our behaviour. Acetylcholine (ACh) is a neuromodulator that is known to be an importantregulator of learning and memory. This project will bring together a variety of in vivo and ex vivo techniques andcomputational analysis to decipher how ACh regulates the processing of learning and memory in the brain's neocortex.The retrosplenial cortex (RSC) is a region of neocortex that is a key node in brain circuit that is essential for learningand memory. In particular, the RSC is important for discriminating between memories of different places, which arecalled spatial memories. The RSC is richly supplied by cholinergic (i.e. ACh releasing) synapses, which indicates thatACh plays an important role in the processing of spatial memories in RSC. We have good evidence that ACh canreconfigure neural activity in RSC, but almost nothing is currently known about how or when ACh is acting to regulatethe processing of spatial memories in RSC.The specific aims of this project are (i) to determine the cellular and synaptic mechanisms by which ACh regulatescommunication between neurons in RSC, and (ii) to determine how ACh regulates the processing of spatial memoriesin RSC. To tackle these aims, you will join a vibrant research community spanning two of the UK's leading researchuniversities, Exeter and Bristol, working alongside a team of 6 postdocs and 10 PhD students across the labs of Dr JonWitton (Exeter), Prof Jack Mellor (Bristol), and Dr Jon Brown (Exeter). You will be trained in cutting-edge ex vivo andin vivo techniques, using a combination of mouse genetics, patch clamp electrophysiology, optogenetics andpharmacology to address aim (i) and in vivo brain imaging and behavioural analysis to tackle aim (ii). You will alsodevelop skills in computer programming by writing novel analytical algorithms.This project will establish a new foundation for understanding how ACh regulates the processing of learning andmemory in cortical brain circuits. This will help to us better understand how disrupted ACh signalling causes learningand memory loss in neurological diseases such as Alzheimer's, and how current ACh boosting drugs (e.g. Donepezil)actually work to enhance cognitive abilities in patients. In summary, this is a highly interdisciplinary project that offersan exceptional training opportunity in an exciting and important field of neuroscience research.