The Spatial and Temporal Scale of Neuromodulation in Mouse Sensory Cortex

小鼠感觉皮层神经调节的时空尺度

• 批准号: 10524638
• 负责人: Jacob Reimer
• 金额: $ 225.14万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10524638
• 关键词: Acetylcholine; Acoustic Stimulation; Alzheimer' s Disease; Anatomy; Animals; Area; Arousal; Attention; Attention deficit hyperactivity disorder; Auditory; Auditory area; Axon; Behavior; Behavioral; Brain; Calcium; Cells; Cues; Data; Dependence; Diffusion; Disease; Down-Regulation; Exploratory Behavior; Feedback; Fluorescent Probes; Frequencies; Future; Global Change; Grain; Health; Human; Image; Interneurons; Kinetics; Locomotion; Measurement; Measures; Methods; Microscope; Modality; Modeling; Mus; Mydriasis; Neuromodulator; Noise; Norepinephrine; Performance; Photic Stimulation; Population; Primates; Proxy; Pupil; Reporting; Resolution; Response to stimulus physiology; Role; Sensory; Shapes; Stimulus; System; Testing; Time; Training; Treatment Efficacy; Up-Regulation; Use of New Techniques; Variant; Visual; Visual Cortex; Work; alertness; autism spectrum disorder; awake; basal forebrain; cholinergic; efficacy evaluation; experimental study; extracellular; human disease; in vivo; locus ceruleus structure; multimodality; neural circuit; neural correlate; neuroregulation; noradrenergic; recruit; relating to nervous system; response; sensor; sensory cortex; spatiotemporal; temporal measurement; transmission process; two-photon; voltage

The neuromodulators acetylcholine (ACh) and norepinephrine (NE) are associated with an activated cortical brain state characterized by an increase in the reliability of cortical responses to external stimuli and enhanced performance on behavioral tasks. A key unresolved question is the spatial and temporal scale at which these neuromodulators exert their effects. New methods to directly record the local availability of ACh and NE simultaneously with the activity of neural populations in mice opens up the possibility to answer this question. In a first set of experiments we will test the hypothesis that neural signatures of the activated state may vary across cortex due to spatial inhomogeneities in moment-to-moment neuromodulator availability. In a second set of experiments we will test the hypothesis that mice can recruit neuromodulators independently to auditory and visual cortex to enhance performance on a multimodal attention task. Given that disruption of these systems is a key feature of a variety of human diseases including Alzheimer’s disease, ADHD, and Autism Spectrum Disorders, understanding the baseline variability in neuromodulator activity in healthy animals will be critical for identifying subtle changes in the effects of neuromodulators that may occur in different disease states and for evaluating the efficacy of treatments. From the perspective of neuroscientists attempting to understand the encoding of stimuli in population activity, the effects of neuromodulators appear as stimulus-independent noise that adds variability to sensory responses. Understanding the spatiotemporal resolution of the effects of ACh and NE will enable modeling of these effects as state variables shaping the response of cortical populations. The cortical effects of both ACh and NE release in mice are strikingly similar to neural correlates of attention recorded in humans and primates. While it is unlikely that mice have fine-grained spatial or feature attention like humans, understanding the spatiotemporal dynamics of these two neuromodulators in mice will be a significant step towards dissociating their influence on attentional mechanisms more generally. Having a clear understanding of the relative time course of the influence of these two neuromodulators on cortical processing will provide important constraints for future studies of the cellular and circuit mechanisms underlying their effects.

神经调节剂乙酰胆碱 (ACh) 和去甲肾上腺素 (NE) 与 激活的皮质脑状态的特征是皮质反应的可靠性增加 外部刺激和行为任务表现的增强是一个尚未解决的关键问题。 这些神经调节剂发挥作用的空间和时间尺度新方法。 直接记录 ACh 和 NE 的局部可用性以及神经活动 在第一组实验中，小鼠群体为回答这个问题提供了可能性。 我们将测试以下假设：激活状态的神经特征可能因皮质而异 由于即时神经调节剂可用性的空间不均匀性。 我们将通过一组实验来检验小鼠可以招募神经调节剂的假设 独立于听觉和视觉皮层，以提高多模式注意力的表现 鉴于这些系统的破坏是多种人类疾病的一个关键特征。 包括阿尔茨海默病、多动症和自闭症谱系障碍，了解 健康动物神经调节剂活性的基线变异对于识别 不同疾病状态下可能发生的神经调节剂作用的微妙变化， 从神经科学家的角度评估治疗效果。 了解群体活动中刺激的编码，神经调节剂的作用出现 作为与刺激无关的噪声，增加了感官反应的可变性。 ACh 和 NE 影响的时空分辨率将使这些影响能够建模为 影响皮质群体反应的状态变量 两种乙酰胆碱的皮质效应。 小鼠中 NE 的释放与记录中记录的注意力的神经相关性惊人地相似 人类和灵长类动物不太可能具有细粒度的空间或特征注意力。 像人类一样，了解小鼠体内这两种神经调节剂的时空动态 将是朝着消除它们对注意力机制的影响迈出的重要一步 一般来说，对这两者的影响的相对时间过程有一个清晰的了解。 皮质处理的神经调节剂将为未来的研究提供重要的限制 其作用背后的细胞和电路机制。