Cholinergic control of the prefrontal cortex in vision

本研究项目旨在了解大鼠自上而下视觉注意的神经生物学机制，特别是胆碱能系统的参与。 视觉感知是由复杂视觉刺激首先在初级视觉皮层（V1），然后在更高的认知皮层区域（关联皮层区域），如后顶叶皮层（PPC）和前额叶皮层（PFC）的整合而产生的。来自PFC的反馈机制，自上而下的注意力，允许增强V1中特定相关刺激的处理。基底前脑（BF）胆碱能神经元通过调节V1和PFC参与自上而下的注意。虽然胆碱能机制在每个皮层区域都有很好的定义，但每个区域之间的功能连接尚不清楚。 拟议研究项目的目标 我们将通过研究1）胆碱能纤维和该通路的不同皮层区域之间的解剖功能连接和2）PFC对V1/胆碱能神经元的自上而下控制来检查胆碱能系统与PFC的相互作用。 将依次分析三个假设： 1.通过对参与高阶视觉加工的不同脑区的胆碱能投射进行离散性和特异性的损伤，研究了胆碱能投射在高阶视觉加工中的不同贡献。 2.胆碱能系统在视觉注意中的作用将通过表面阵列电生理学在大鼠中进行研究，并通过宽场钙成像在唤醒的GCaMP 6小鼠中进行研究。在有或没有胆碱能系统刺激或损伤的视觉注意任务期间，将建立不同区域之间的连接图。 3. PPC在从PFC到视皮层的自上而下控制中的作用将被研究。 结论 我们希望显示PFC参与需要注意的视觉辨别任务，这可能会激活投射到V1的HDB神经元。这种影响将通过行为分析结合功能神经解剖学和追踪来确定。将确定所涉及的神经元的神经化学性质以及优先激活的皮质层和亚区。

This research program is related to the understanding of the neurobiological mechanisms of top-down visual attention in the rat, particularly in regard to the involvement of the cholinergic system. Visual perception results from the integration of complex visual stimuli first in the primary visual cortex (V1) and then in higher cognitive cortical areas (association cortical areas), such as the posterior parietal cortex (PPC) and the prefrontal cortex (PFC). A feedback mechanism from the PFC, top down attention, allows to enhance processing of specific relevant stimuli in V1. Basal forebrain (BF) cholinergic neurons contribute to top down attention by modulation of V1 and PFC. Although cholinergic mechanisms are quite well defined in each cortical area, the functional connectivity between each area is not well known. Objectives of the proposed research project We will examine the interaction of the cholinergic system with PFC by studying 1) the anatomo-functional connectivity between the cholinergic fibers and the different cortical areas of this pathways and 2) the top down control of V1/cholinergic neurons by PFC. Three hypotheses will be successively analyzed: 1. The differential contribution of the cholinergic projections in high order visual processing will be investigated by discrete and specific lesion of the cholinergic projections in the different regions involved in visual processing during a high order visual task. 2. The role of the cholinergic system in visual attention will be investigated in the rat with surface array electrophysiology and awaken GCaMP6 mice by wide field calcium imaging. Connection diagrams between the different areas will be established during a visual attention task with or without cholinergic system stimulation or lesion. 3. The role of PPC in the top-down control from PFC to visual cortex will be investigated. Conclusion We expect to show an involvement of the PFC on the visual discrimination task requiring attention, possibly which would activate HDB neurons that project to V1. This influence would be determined by behavioural analysis combined with functional neuroanatomy, and track tracing. The neurochemical nature of the neurons involved will be determined as well as the cortical layers and subregions preferentially activated.