Mechanisms and Purpose of Top-down Neural Activity Generation Across Conscious States: DREAMNET

Programme(s): HORIZON.1.1 - European Research Council (ERC) 

Topic(s): ERC-2022-COG - ERC CONSOLIDATOR GRANTS

Call for proposal: ERC-2022-COG

Funding Scheme: HORIZON-ERC - HORIZON ERC Grants

Grant agreement ID: 101088598

Objective:

Sleep is universal in mammals, yet the origin, structure and purpose of the neural activity patterns which permeate this state remains highly contentious. This is largely because such activity is internally generated and thus not amenable to most traditional methods of analysis. Here I propose top-down circuits in cortical layer 1 as a key site of production and structuring of neural activity during sleep, and detail novel experimental and analysis approaches to probe layer 1 circuits across sleep states at synaptic resolution. Layer 1 of the sensory cortex receives long distance signals from higher cortical regions which during wakefulness powerfully modulate sensory processing, and underpin neurocognitive processes such as attention, prediction, and sensorimotor integration. Such top-down circuits are well placed to autonomously generate activity during sleep which is meaningfully structured in the absence of sensory input. I propose that such top-down activations, unconstrained by the sensory environment, but structured by a lifetime of synaptically encoded experience stored in cortical connectivity patterns, could promote the formation of meaningful associations and insights inaccessible and cognitively disruptive if produced in waking states. I propose to test this mechanism and purpose of sleep activations using in vivo multiphoton imaging in mice: high resolution synaptic imaging will allow measurement of the origin and regulation (Aim 1), content, structure (Aim 2), and development (Aim 3) of top-down signals to layer 1 during different conscious states and will answer fundamental questions regarding the interplay between sleeping and waking activity patterns and their brain-wide propagation. We anticipate the work will lead to a fundamental advance in our understanding of micro and macro architecture of neural activations during sleep and in doing so resolve long running questions as to the mnemonic, creative, and maintenance functions of such activity.