Plasticity of cortical networks during learning

项目概要： 可塑性发生在初级视觉皮层（V1），以响应视觉联想学习，其中一个 一个刺激与奖赏配对（CS+），另一个刺激与奖赏配对（CS-）。然而，学习不是一个单一的过程， 不同的学习阶段可能会驱动V1的对比可塑性变化。事实上，以前的研究发现， 在整个学习过程中，V1锥体神经元活动和输入在不同时间的动态变化。实验 缺乏从行为上区分不同的学习阶段，这使得很难完全剖析V1可塑性 在学习过程中的变化。为了解决这个问题，我们设计了一个3阶段的联想学习任务， 将早期刺激非特异性学习与晚期刺激特异性学习和逆转学习分开。我们 也会以两种方式操纵刺激值：贬值和去除喷口。利用这种行为模式 沿着小鼠背侧皮质的1-和2-光子钙成像，我们将测试以下假设：1） 视觉联想学习在不同的学习阶段不同地招募V1活动，2）V1活动是 V1神经元对刺激值的变化具有快速可塑性，3）单个V1神经元表现出双向可塑性 在整个学习过程中，4）视觉联想学习改变皮质-皮质功能连接，5）V1活动 是维持这些皮质-皮质功能连接变化所必需的。我们的结果将提供一个 在整个学习和刺激值操纵中对V1可塑性的前所未有的深入了解。我们会的 第一次，解决V1的可塑性如何反映在背侧皮层上，或者是皮质-皮质的 可塑性。

PROJECT SUMMARY: Plasticity occurs in the primary visual cortex (V1) in response to visual associative learning, where one stimulus is paired with reward (CS+) and another is not (CS-). However, learning is not a unitary process, and distinct stages of learning might drive contrasting plastic changes in V1. Indeed, previous work has found dynamic changes in V1 pyramidal neuron activity and inputs at different times throughout learning. Experiments separating distinct learning phases behaviorally are lacking, making it difficult to fully dissect V1 plasticity changes throughout learning. To address this, we have designed a 3-phase associative learning task that separates early, stimulus non-specific learning from late, stimulus-specific learning and reversal learning. We will also manipulate stimulus value in two ways: devaluation and spout removal. Using this behavioral paradigm along with 1- and 2-photon calcium imaging of the mouse dorsal cortex, we will test the following hypotheses: 1) that visual associative learning differentially recruits V1 activity during distinct learning stages, 2) activity in V1 is rapidly plastic in response to changes in stimulus value, 3) individual V1 neurons exhibit bidirectional plasticity across learning, 4) visual associative learning changes cortico-cortical functional connectivity, and 5) V1 activity is required to maintain these cortico-cortical functional connectivity changes. Our results will provide an unprecedented level of insight into V1 plasticity throughout learning and stimulus value manipulation. We will, for the first time, address how plasticity in V1 is mirrored across the dorsal cortex, or required for cortico-cortical plasticity.