Neuromodulatory and astrocyte influences on hippocampal place cell plasticity

项目总结/摘要 星形胶质细胞在回路功能中的作用，特别是在神经可塑性方面， 探索，但争论。研究神经可塑性的一个很好的大脑区域是海马体，因为 它的神经元代表世界的认知相关维度， 行为相关的方式。海马体中含有位置细胞， 环境，并显示与行为相关的重组结构，例如在奖励 位置.这发生在小鼠的目标导向学习（GOL）任务中。多巴胺（DA）是一种良好的 候选神经调质影响奖励相关的重新映射，因为已知它影响神经元的功能。 定位细胞的稳定性。海马中DA的来源最近被证明是 蓝斑（LC），其也释放去甲肾上腺素（NE）。LC在GOL期间的作用尚不清楚。 学习时LC释放的NE和DA可直接作用于神经元， 影响星形胶质细胞。皮质星形胶质细胞对NE的反应是钙水平的巨大变化，但这一变化可能与NE的作用有关。 还没有在海马体中被检测到。这些钙反应可能会导致 神经网络函数本提案将审查1）LC预测活动， 海马和星形胶质细胞钙在GOL 2）LC轴突活性和 星形胶质细胞钙，3）LC对奖励相关的位置细胞重映射的影响，4）以及LC是否 对定位细胞的作用需要完整的星形胶质细胞钙。我假设LC活动导致了定位细胞 通过对星形胶质细胞钙水平的影响向奖赏区转移。我会检查这些 问题使用双光子钙成像在清醒，行为小鼠。更好地理解 神经调节、星形胶质细胞功能和神经可塑性之间的关系将产生新的 关于电路功能和病理学的理论。

Project Summary/Abstract The role of astrocytes in circuit function, particularly with respect to neural plasticity, has been explored but is debated. One excellent brain area to study neural plasticity is the hippocampus, since it has neurons that represent cognitively relevant dimensions of the world that change in a behaviorally relevant manner. The hippocampus contains place cells that represent locations in the environment, and show reorganized restructuring relevant to behavior, for example at a reward location. This occurs during goal-oriented learning (GOL) tasks in mice. Dopamine (DA) is a good candidate neuromodulator to influence reward-related remapping, since it is known to affect the stability of place cells. The source of DA in the hippocampus was recently shown to be the locus coeruleus (LC), which also releases norepinephrine (NE). The role of the LC during GOL is unknown. NE and DA released from the LC during learning could act directly on neurons, but it could also influence astrocytes. Astrocytes in cortex respond to NE with large changes in calcium levels, but this has not been examined in the hippocampus. These calcium responses may cause alterations in neural network function. This proposal will examine 1) the activity of LC projections to the hippocampus and astrocyte calcium during GOL 2) the relationship between LC axon activity and astrocyte calcium, 3) the LC’s effect on reward-related place cell remapping, 4) and whether the LC’s effect on place cells requires intact astrocyte calcium. I hypothesize that LC activity causes place cell shifts toward the reward zone via its effects on astrocyte calcium levels. I will examine these questions using two-photon calcium imaging in awake, behaving mice. A better understanding of the relationship between neuromodulation, astrocyte function, and neural plasticity will generate new theories about circuit function and pathology.