Common modular architecture across diverse cortical areas in early development

Abstract

In order to deal with a complex environment, animals form a diverse range of neural representations that vary across cortical areas, ranging from largely unimodal sensory input to higher-order representations of goals, outcomes, and motivation. The developmental origin of this diversity is currently unclear, as representations could arise through processes that are already area-specific from the earliest developmental stages or alternatively, they could emerge from an initially common functional organization shared across areas. Here, we use spontaneous activity recorded with two-photon and widefield calcium imaging to reveal the functional organization across the early developing cortex in ferrets, a species with a well-characterized columnar organization and modular structure of spontaneous activity in the visual cortex. We find that in animals 7 to 14 d prior to eye-opening and ear canal opening, spontaneous activity in both sensory areas (auditory and somatosensory cortex, A1 and S1, respectively), and association areas (posterior parietal and prefrontal cortex, PPC and PFC, respectively) showed an organized and modular structure that is highly similar to the organization in V1. In all cortical areas, this modular activity was distributed across the cortical surface, forming functional networks that exhibit millimeter-scale correlations. Moreover, this modular structure was evident in highly coherent spontaneous activity at the cellular level, with strong correlations among local populations of neurons apparent in all cortical areas examined. Together, our results demonstrate a common distributed and modular organization across the cortex during early development, suggesting that diverse cortical representations develop initially according to similar design principles.

Keywords: cortex; development; network.

Fig. 1.

Spontaneous activity is highly modular in early development across diverse cortical areas. (A) Experimental schematic. Spontaneous activity was imaged at P21-24, 7 to 14 d prior to eye-opening and ear canal opening. (B) Activity was imaged in primary somatosensory (S1), auditory (A1), and visual (V1) cortices, and in the association areas PFC and PPC. (C) Time course of spontaneous activity (mean activity across ROI) in each brain area imaged in independent experiments. (D) Individual spontaneous events (times indicated in C) show highly modular activity in all areas. (E) The modularity of spontaneous events does not vary across cortical areas. For panels (E–G): Left plot shows distribution across all events, Right plot shows median of distribution for each animal (dots) and mean across animals (horizontal bar). (F) The wavelength of activity for spontaneous events is similar across events from different areas. (G) Module amplitude (active module vs. adjacent cortex) is generally similar across areas, with significantly lower amplitude in S1 and higher amplitude in V1. Significant post hoc pairwise comparisons indicated by horizontal lines. Error bars ± SEM.

Fig. 2.

Diverse cortical areas show distributed and modular long-range correlations. (A) Correlations across spontaneous events reveal distributed and modular networks that extend across several millimeters in both sensory and association areas. Pixelwise correlations are shown for two different seed points (Top/Bottom), revealing the presence of multiple distributed modular networks within each cortical region. (B, Left) The strength of correlations declines with distance in all cortical areas, remaining statistically significant vs. surrogate controls (dashed lines, 1 per area) up to at least 2 mm, the limits of our imaging window. (Right) The strength of long-range correlations (1.8 to 2.2 mm away from seed point) is similar across areas. Dots show individual animals, horizontal bar indicates mean across animals. Open squares show mean ± SEM for surrogate controls. (C) Spontaneous activity is moderately low dimensional in all cortical areas. Variance explained by principal components (Left) and participation ratio of spontaneous activity (Right) are similar across areas. Significant post hoc pairwise comparisons indicated by horizontal lines. Error bars ± SEM.

Fig. 3.

Spontaneous activity shows strong local organization with cellular resolution across the cortex. (A) Modular organization of spontaneous activity in layer 2/3 neurons is evident in individual events. (B) Activity across events is locally correlated and modular. Correlations for individual neurons are shown relative to seed neuron (in green) and are overlaid on correlations from widefield imaging in the same animal (see below), showing a strong correspondence between millimeter-scale networks in widefield imaging and local organization at the cellular level. (C) Widefield correlation patterns for seed point matching location of seed neuron shown in (B). Box indicates 2-photon FOV shown in (A and B). (D, Left) The amplitude of correlations between neurons shows a similar pattern with distance across areas. (Right) Nearby correlations (30 to 100 µm) are strong in all cases. Correlations in S1 are significantly weaker than other areas. (E) LCI of spontaneous correlations shows highly organized functional networks. (Left) The reversal from positive to negative correlations occurs at a similar distance in all cortical areas. (Right) Coherence is nearly uniform (near 1) for nearby populations of neurons (30 to 100 µm). (F) Dimensionality of spontaneous activity within local populations of neurons is moderately low and does not vary significantly across areas. (Left) Cumulative variance explained and (Right) participation ratio for populations of 50 neurons in each area. Horizontal lines in (D and E) indicate significant post hoc pairwise comparisons. Error bars ± SEM.