Cholinergic control of the prefrontal cortex in vision

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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.