Self-organization of modular activity in immature cortical networks.

During development, cortical activity is organized into distributed modular patterns that are a precursor of the mature columnar functional architecture. Theoretically, such structured neural activity can emerge dynamically from local synaptic interactions through a recurrent network with effective local excitation with lateral inhibition (LE/LI) connectivity. Utilizing simultaneous widefield calcium imaging and optogenetics in juvenile ferret cortex prior to eye opening, we directly test several critical predictions of an LE/LI mechanism. We show that cortical networks transform uniform stimulations into diverse modular patterns exhibiting a characteristic spatial wavelength. Moreover, patterned optogenetic stimulation matching this wavelength selectively biases evoked activity patterns, while stimulation with varying wavelengths transforms activity towards this characteristic wavelength, revealing a dynamic compromise between input drive and the network's intrinsic tendency to organize activity. Furthermore, the structure of early spontaneous cortical activity - which is reflected in the developing representations of visual orientation - strongly overlaps that of uniform opto-evoked activity, suggesting a common underlying mechanism as a basis for the formation of orderly columnar maps underlying sensory representations in the brain.

Common modular architecture across diverse cortical areas in early development.

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.

Self-organization of modular activity in immature cortical networks.

During development, cortical activity is organized into distributed modular patterns that are a precursor of the mature columnar functional architecture. Theoretically, such structured neural activity can emerge dynamically from local synaptic interactions through a recurrent network with effective local excitation with lateral inhibition (LE/LI) connectivity. Utilizing simultaneous widefield calcium imaging and optogenetics in juvenile ferret cortex prior to eye opening, we directly test several critical predictions of an LE/LI mechanism. We show that cortical networks transform uniform stimulations into diverse modular patterns exhibiting a characteristic spatial wavelength. Moreover, patterned optogenetic stimulation matching this wavelength selectively biases evoked activity patterns, while stimulation with varying wavelengths transforms activity towards this characteristic wavelength, revealing a dynamic compromise between input drive and the network's intrinsic tendency to organize activity. Furthermore, the structure of early spontaneous cortical activity - which is reflected in the developing representations of visual orientation - strongly overlaps that of uniform opto-evoked activity, suggesting a common underlying mechanism as a basis for the formation of orderly columnar maps underlying sensory representations in the brain.

All-optical interrogation of millimeter-scale networks and application to developing ferret cortex.

BACKGROUND: Perception and behavior require coordinated activity of thousands of neurons operating in networks that span millimeters of brain area. In vivo calcium imaging approaches have proven exceptionally powerful for examining the structure of these networks at large scales, and optogenetics can allow for causal manipulations of large populations of neurons. However, realizing the full potential of these techniques requires the ability to simultaneously measure and manipulate distinct circuit elements on the scale of millimeters. NEW METHOD: We describe an opto-macroscope, an artifact-free, all-optical system capable of delivering patterned optogenetic stimulation with high spatial and temporal resolution across millimeters of brain while simultaneously imaging functional neural activity. RESULTS: We find that this approach provides direct manipulation of cortical regions ranging from hundreds of microns to several millimeters in area, allowing for the perturbation of individual brain areas or networks of functional domains. Using this system we find that spatially complex endogenous networks in the developing ferret visual cortex can be readily reactivated by precisely designed patterned optogenetic stimuli. COMPARISON WITH EXISTING METHODS: Our opto-macroscope extends current all-optical optogenetic approaches which operate on a cellular scale with multiphoton stimulation, and are poorly suited to investigate the millimeter-scale of many functional networks. It also builds upon other mesoscopic optogenetic techniques that lack simultaneous optical readouts of neural activity. CONCLUSIONS: The large-scale all-optical capabilities of our system make it a powerful new tool for investigating the contribution of cortical domains and brain areas to the functional neural networks that underlie perception and behavior.

Tightly coupled inhibitory and excitatory functional networks in the developing primary visual cortex.

Intracortical inhibition plays a critical role in shaping activity patterns in the mature cortex. However, little is known about the structure of inhibition in early development prior to the onset of sensory experience, a time when spontaneous activity exhibits long-range correlations predictive of mature functional networks. Here, using calcium imaging of GABAergic neurons in the ferret visual cortex, we show that spontaneous activity in inhibitory neurons is already highly organized into distributed modular networks before visual experience. Inhibitory neurons exhibit spatially modular activity with long-range correlations and precise local organization that is in quantitative agreement with excitatory networks. Furthermore, excitatory and inhibitory networks are strongly co-aligned at both millimeter and cellular scales. These results demonstrate a remarkable degree of organization in inhibitory networks early in the developing cortex, providing support for computational models of self-organizing networks and suggesting a mechanism for the emergence of distributed functional networks during development.

Visual processing: Systematic variation in light-dark bias across visual space.

Detecting changes in luminance is a fundamental property of the visual system. A new study shows that lights and darks are represented differently across visual space, with strong OFF bias in central vision and balanced ON/OFF in the periphery.