Investigating cortical readout of temporal codes for olfaction

研究嗅觉时间编码的皮层读数

• 批准号: 10464988
• 负责人: Robin Blazing
• 金额: $ 3.9万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10464988
• 关键词: Address; Alzheimer' s Disease; Animal Model; Behavior; Behavioral; Biological Markers; Brain; Cells; Code; Complex; Data; Dementia; Disease; Electrodes; Exhibits; Feedback; Future; Goals; Head; Human; Individual; Light; Mediating; Memory; Methods; Modeling; Mus; Neurons; Odors; Olfactory Pathways; Olfactory dysfunction; Pattern; Population; Property; Protocols documentation; Reader; Recurrence; Respiration; Rest; Sensory; Sensory Process; Shapes; Smell Perception; Specificity; Stereotyping; Stimulus; Structure; System; Techniques; Technology; Testing; Time; Work; awake; cell cortex; cell type; cognitive process; experimental study; insight; memory retrieval; millisecond; neural patterning; olfactory bulb; olfactory bulb glomeruli; operation; optogenetics; piriform cortex; postsynaptic; relating to nervous system; response; spatiotemporal; temporal measurement

ABSTRACT In the brain, stereotyped sequences of neural activity have been shown to correlate with a diverse array of behaviors and cognitive processes. While neural sequences have been characterized extensively from an encoding perspective, the effects of sequence activity on downstream reader networks remain relatively unexplored. A key example is in the olfactory system, where odors activate stereotyped spatiotemporal sequences of olfactory bulb glomeruli. The temporal structure of glomerular activity is thought to convey information about odor quality to the rest of the brain. However, the sensitivity of populations of neurons in downstream piriform cortex (PCx) to the precise timing of glomerular sequences is not known. Recent advances in light patterning technologies have made it possible to optogenetically activate sequences of glomeruli with high temporal precision, providing a means to investigate the independent impact of sequence timing on neural activity in PCx. In my early graduate work, I built and validated a system to perform patterned optogenetic stimulation of olfactory bulb glomeruli in awake mice. I established methods to use this system in tandem with multichannel electrode recordings of large populations of neurons in PCx. In preliminary experiments, I have observed that population activity in PCx is highly dependent on the precise timing of glomerular responses. In this proposal, I will test the central hypothesis that intra-cortical recurrent circuits enforce the precise readout of sequential inputs to PCx. In my first aim, I will determine how individual PCx cells integrate temporally distributed inputs. Then, in aims 2 and 3, I will use cell-type specific optogenetics to delineate the respective contributions of intra-cortical inhibition and recurrent excitation within PCx to these temporally specific responses. The results of these experiments will provide a quantitative and mechanistic understanding of how neural sequence readout is coordinated in cortical circuits.

摘要 在大脑中，刻板的神经活动序列已被证明与多种多样的阵列相关 行为和认知过程。虽然神经序列已被广泛地表征， 从编码的角度来看，序列活动对下游读者网络的影响仍然相对较小。 未开发的一个关键的例子是嗅觉系统，气味激活了刻板的时空 嗅球小球的序列。肾小球活动的时间结构被认为传达了 气味质量的信息传递到大脑的其他部分。然而，神经元群体的敏感性， 下游梨状皮质（PCx）的肾小球序列的精确定时是未知的。最新进展 光图案化技术已经使得光遗传学激活肾小球序列成为可能， 高时间精度，提供了一种手段，调查独立的影响，序列计时神经 PCx的活动。在我早期的研究生工作中，我建立并验证了一个系统， 刺激清醒小鼠嗅球肾小球。我建立了方法来使用这个系统， PCx中大量神经元的多通道电极记录。在初步实验中，我 观察到PCx中的群体活性高度依赖于肾小球反应的精确时间。在 这个建议，我将测试的核心假设，即皮层内循环回路执行的精确读出， PCx的顺序输入。在我的第一个目标中，我将确定单个PCx细胞如何在时间上分布 输入。然后，在目标2和3中，我将使用细胞类型特异性光遗传学来描述各自的贡献 皮层内抑制和PCx内的反复兴奋对这些时间特异性反应的影响。结果 这些实验将提供一个定量和机械的理解如何神经序列读出 是在皮层回路中协调的