Investigating cortical readout of temporal codes for olfaction

摘要 在大脑中，神经活动的刻板序列已被证明与不同的阵列相关 行为和认知过程。虽然神经序列已经从一个 从编码角度来看，序列活动对下游阅读器网络的影响仍然相对较大 未被开发的。一个关键的例子是在嗅觉系统中，气味激活了刻板的时空 嗅球肾小球序列。肾小球活动的时间结构被认为传达了 关于气味质量的信息传给大脑的其余部分。然而，神经元群体的敏感度 梨状皮质下游(PCX)到肾小球的确切时间序列尚不清楚。最新进展 在光图案化技术中，已经有可能通过光基因激活肾小球序列 高时间精度，提供了一种研究序列计时对神经的独立影响的方法 在PCX中的活动。在我早期的研究生工作中，我构建并验证了一个系统来执行图案化的光遗传 对清醒小鼠嗅球肾小球的刺激。我建立了一些方法来配合使用这个系统 PCX内大量神经元的多通道电极记录。在初步实验中，我有 观察到，PCX中的群体活动高度依赖于肾小球反应的准确时间。在……里面 在这项提议中，我将检验一个中心假设，即皮质内循环回路强制执行准确的读数 PCX的顺序输入。在我的第一个目标中，我将确定单个PCX细胞如何整合时间分布 投入。然后，在目标2和目标3中，我将使用细胞类型特定的光遗传学来描述各自的贡献 皮层内抑制和PCX内对这些时间特异性反应的反复兴奋。结果是 这些实验将提供对神经序列读出的定量和机械性的理解 是在大脑皮层回路中协调的。

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.