Self-organizing circuit mechanisms of large-scale functional networks in the developing visual cortex

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Self-organizing circuit mechanisms of large-scale functional networks in the developing visual cortex

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2023-05

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The neural circuits that are established during development have a profound impact on the functioning of the adult brain. Over the course of development, the cortical neurons must organize themselves into large-scale networks that prepare the brain to interpret peripheral sensory inputs into meaningful perceptual outputs. Stimulus evoked activity in the primary visual cortex is organized into spatially modular functional networks with both local and global order, as is exemplified in the periodic arrangement of orientation preference found in primates and carnivores. These networks are established early in development prior to visual experience, where intrinsically generated spontaneous activity reveals large-scale functional networks that predict the future functional maps. Computational models of cortical network development have long hypothesized that modular activity could emerge through a Turing mechanism, which self-organizes unstructured inputs into spatially modular outputs via short-range interactions within a recurrently connected network of local excitation with lateral inhibition. However, critical predictions of this mechanism have not been tested in vivo. Utilizing in vivo calcium imaging and optogenetic modulation of neural activity in the developing ferret primary visual cortex, we investigated the circuit mechanisms underlying the development of large-scale functional networks for visual perception. Circuit mechanisms involving competitive intracortical interactions require spatially precise inhibitory signaling; however, the organization of inhibitory activity in the developing visual cortex was unknown. We found that prior to eye opening, the spontaneous activity of inhibitory interneurons is organized into modular patterns that reveal large-scale correlated networks that are tightly coupled with excitatory neural activity. We next tested whether developing cortical networks self-organize to produce modular patterns of activity. Optogenetic stimulation with a uniform input led to a break in neural symmetry consistent with a Turing instability, producing a diverse array of spatially modular patterns. These modular patterns arise through intracortical interactions, and do not require structured feedforward input to become modular. Opto-evoked patterns are highly similar to the patterns seen in spontaneous activity, suggesting that spontaneous activity also emerges through the same intracortical interactions. Finally, we tested whether early cortical networks have preferentially connected recurrent subnetworks, which would lead to the amplification of stimulus inputs that align well with the structure of those networks. We found that stimulating with spatial patterns that overlap with those that can be produced by the endogenous network drove more reliable responses than stimulating with artificial stimuli. Further, artificial input patterns do not create new structures, but instead evoke output activity that resides within the endogenous network, consistent with a transformation through a recurrent network with attractor dynamics. Altogether, this body of work provides strong evidence supporting the hypothesis that the modular patterns of neural activity seen early in development emerge through a dynamic self-organizing mechanism of intracortical interactions. Developing cortical networks prior to visual experience already show remarkable degree of organization, including spatially precise inhibition and preferentially biased recurrent interactions within functional subnetworks, highlighting the importance of early cortical activity in establishing large-scale functional networks for visual perception.

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University of Minnesota Ph.D. dissertation. May 2023. Major: Neuroscience. Advisor: Gordon Smith. 1 computer file (PDF); viii, 136 pages + 2 supplementary files.

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Mulholland, Haleigh. (2023). Self-organizing circuit mechanisms of large-scale functional networks in the developing visual cortex. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/264337.

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