Mechanisms governing development of large-scale networks in visual cortex

University Of Minnesota, Minneapolis MN

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Abstract

Project Summary/Abstract Sensory perception requires the coordinated activity of tens of thousands of neurons functioning together in large-scale networks. The capabilities of these networks are defined and constrained by their development, yet the mechanisms underlying their formation remain incompletely understood. In the visual cortex of primates and carnivores, modular networks consisting of nearby neurons sharing coordinated activity and similar tuning properties extend across millimeters of cortical surface. Prior to eye-opening, such large-scale networks are already evident in correlated spontaneous activity, whose structure can predict future visually-evoked responses. We have previously shown that local recurrent mechanisms utilizing local excitation / lateral inhibition (LELI) interactions account for these modular functional networks in the week prior to eye-opening. However, major gaps remain in our ability to relate early network structure to mature sensory function. All previous work occurred at ages when spontaneous activity is already modular, meaning that its developmental origins remain unclear. Furthermore, early modular networks undergo refinement prior to eye-opening, but the role of changes in recurrent interactions versus changes in inputs is unknown. The experiments in this proposal will address these gaps, first by imaging spontaneous activity earlier in development than prior work, beginning at an age when cortical neurons are still completing their migration. This will allow us to capture the onset of modular activity in the cortex and investigate whether the same mechanisms that underlie modular activity later in development are also involved from the earliest stages. In order to determine if intracortical circuits are responsible for generating dominant modes of activity that refine in the week prior to eye-opening and serve as a dynamic scaffold for future visual representations, we will utilize our ability to directly stimulate the cortex with spatially-patterned optogenetics. These experiments will allow us to separate the contributions of changes in input from those of changes within recurrent circuits to both the developmental refinement of cortical networks and their potential role as a template for the future structure of visually-evoked representations. Finally, in order to understand whether a modular organization generated through recurrent LELI mechanisms exists elsewhere in visual cortices, we will image spontaneous activity in higher visual areas throughout development, and use patterned optogenetic stimulation to directly test the role of LELI mechanisms outside V1. Understanding the mechanisms through which modular network structure first emerges and whether recurrent circuits serve to generate dominant modes of activity that function as templates for sensory representations is critical for understanding how functional visual circuits are constructed during development. Determining if such mechanisms operate throughout higher visual areas is key for understanding the function organization of these regions. Collectively, the studies in this proposal will provide critical new insights into both the developmental origins of millimeter- scale functional networks and their role in shaping future functional organization throughout the visual cortex.