Abstract

Correlations in local neocortical spiking activity can provide insight into the underlying organization of cortical microcircuitry. However, identifying structure in patterned multi-neuronal spiking remains a daunting task due to the high dimensionality of the activity. Using two-photon imaging, we monitored spontaneous circuit dynamics in large, densely sampled neuronal populations within slices of mouse primary auditory, somatosensory, and visual cortex. Using the lagged correlation of spiking activity between neurons, we generated functional wiring diagrams to gain insight into the underlying neocortical circuitry. By establishing the presence of graph invariants, which are label-independent characteristics common to all circuit topologies, our study revealed organizational features that generalized across functionally distinct cortical regions. Regardless of sensory area, random and -nearest neighbors null graphs failed to capture the structure of experimentally derived functional circuitry. These null models indicated that despite a bias in the data towards spatially proximal functional connections, functional circuit structure is best described by non-random and occasionally distal connections. Eigenvector centrality, which quantifies the importance of a neuron in the temporal flow of circuit activity, was highly related to feedforwardness in all functional circuits. The number of nodes participating in a functional circuit did not scale with the number of neurons imaged regardless of sensory area, indicating that circuit size is not tied to the sampling of neocortex. Local circuit flow comprehensively covered angular space regardless of the spatial scale that we tested, demonstrating that circuitry itself does not bias activity flow toward pia. Finally, analysis revealed that a minimal numerical sample size of neurons was necessary to capture at least 90 percent of functional circuit topology. These data and analyses indicated that functional circuitry exhibited rules of organization which generalized across three areas of sensory neocortex.

Highlights

  • Transmission and processing of information in the brain is in large part determined by the connectivity between neurons [1]

  • We sought to evaluate whether functional circuit architecture generalizes across the neocortex, testing the existence of a functional analogue to the neocortical microcircuit hypothesis

  • Formation of functional topology To determine whether A1, S1, and V1 functional circuit wiring diagrams exhibited invariant features, we monitored neuronal activity in 43 slices from each region of the mouse neocortex (11 of A1, 21 of S1, and 11 of V1) using high speed multi-photon calcium imaging [15,25,31]

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Summary

Introduction

Transmission and processing of information in the brain is in large part determined by the connectivity between neurons [1]. The neocortical microcircuit hypothesis states that the neocortex is composed of repeated elements of a generalized circuit that are tweaked for specialization in each area [2] Supporting this hypothesis, local synaptic connectivity in the neocortex is nonrandom and is at least partly determined by neuron location and class [2,3,4,5,6,7,8,9,10,11,12]. Modeling studies have shown a clear relationship between connectivity and neural firing [15,20,21,22,23,24] This suggests that we can gain insight into the underlying structure and organization of cortical circuitry by analyzing the emergent dynamics of large populations of neocortical neurons

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