The synaptic basis of learning and attention

学习和注意力的突触基础

• 批准号: 2723242
• 金额: --
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2723242
• 关键词: synaptic; basis; learning; attention

Animals are remarkably adept at flexibly adapting their behaviour, and this ability isessential for survival in an ever-changing environment. During learning (over days),and attention (over seconds), neurons change their response properties, sharpeningtheir responses to relevant features of the environment. This plasticity depends onchanges in the tens of thousands of excitatory synapses and several thousandinhibitory synapses present on each neuron. Changes in individual synapses duringlearning are challenging to study. Even when average changes in synaptic propertiesare known, it is not straightforward to relate then to the changes in the properties ofindividual neurons as they function in a network. Thus, it remains poorly understoodwhether learning relies on changes in a small number of strong synapses, or morewidely distributed changes across a large number of synapses. Are synaptic changesclustered, to drive non-linear dendritic events? Are most synaptic changes duringlearning and attention top-down (in apical dendrites) or bottom up (in basal dendrites),or is there transfer across these domains over days? This project will address thesequestions by measuring activity in individual synaptic spines using multi-day in-vivotwo-photon calcium imaging in visual cortex as mice learn a visual discrimination taskand subsequently perform an attention-switching task (Poort... Khan et al 2022). Thesetechniques are already established and routinely used in the host lab. We will use amultidisciplinary approach, including optogenetics, imaging GCaMP7f fused with PSD-95 Fingrs and gephyrin-Fingrs, and computational modeling. The activity of individualspines will be related the activity of the soma of the same neurons and the mousebehaviour. Finally, we will investigate how the local balance of excitatory andinhibitory synapses on short stretches of dendrites is modified and how this relates toplasticity in cortical neurons (Grillo... Burrone et al Neuron 2018).

动物非常善于灵活地调整自己的行为，这种能力对于在不断变化的环境中生存至关重要。在学习（几天）和注意力（几秒钟）的过程中，神经元改变了它们的反应特性，使它们对环境的相关特征的反应更加敏锐。这种可塑性取决于存在于每个神经元上的数万个兴奋性突触和数千个抑制性突触的变化。学习过程中个体突触的变化是一项具有挑战性的研究。即使知道突触特性的平均变化，也不能直接将其与单个神经元在网络中起作用时的特性变化联系起来。因此，对于学习是依赖于少数强突触的变化，还是依赖于更广泛分布在大量突触上的变化，人们仍然知之甚少。突触变化是否聚集在一起，从而驱动非线性树突事件？在学习和注意过程中，大多数突触变化是自上而下的（在顶端树突中）还是自下而上的（在基底树突中），或者这些区域之间的转移是在几天内发生的？这个项目将通过测量单个突触棘的活动来解决这些问题，在小鼠学习视觉辨别任务和随后执行注意力转换任务时，使用多日体内双光子钙成像在视觉皮层中测量单个突触棘的活动。Khan et al 2022)。这些技术已经建立并在宿主实验室中常规使用。我们将采用多学科的方法，包括光遗传学，成像GCaMP7f与PSD-95手指和gephyrin-手指融合，以及计算建模。单个脊髓的活动将与相同神经元的胞体活动和小鼠行为相关联。最后，我们将研究树突短链上兴奋性和抑制性突触的局部平衡是如何被改变的，以及这与皮质神经元的可塑性有何关系(Grillo…Burrone et al Neuron 2018)。