Neocortical Microcircuits 1 Abbreviated title : Acetylcholine Functionally

41 Sensory information is processed and transmitted through the synaptic structure of local cortical 42 circuits, but it is unclear how modulation of this architecture influences the cortical 43 representation of sensory stimuli. Acetylcholine (ACh) promotes attention and arousal and is 44 thought to increase the signal-to-noise ratio of sensory input in primary sensory cortices. Using 45 high-speed 2-photon calcium imaging in a thalamocortical somatosensory slice preparation, we 46 recorded action potential activity of up to 900 neurons simultaneously and compared local 47 cortical circuit activations with and without bath presence of ACh. We found that ACh reduced 48 weak pairwise relationships and excluded neurons that were already unreliable during circuit 49 activity. Using action potential activity from the imaged population, we generated functional 50 wiring diagrams based on the statistical dependencies of activity between neurons. ACh pruned 51 weak functional connections from spontaneous circuit activations and yielded a more modular 52 and hierarchical circuit structure, which biased activity to flow in a more feedforward fashion. 53 Neurons that were active in response to thalamic input had reduced pairwise dependencies 54 overall, but strong correlations were conserved. This coincided with a prolonged period during 55 which neurons showed temporally precise responses to thalamic input. Our results demonstrate 56 that ACh reorganizes functional circuit structure in a manner that may enhance the integration 57 and discriminability of thalamic afferent input within local neocortical circuitry. 58