Functional organization and development of connectivity in L2/3 of mouse primary visual cortex

It is a fundamental goal of neuroscience to understand how feature-selective sensory response properties of cortical neurons emerge from the highly structured synaptic organization of the cortex. This thesis describes the receptive field (RF) organization in L2/3 of mouse primary visual cortex (V1)...

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Bibliographic Details
Main Author: Cossell, L.
Published: University College London (University of London) 2014
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Online Access:http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.631923
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Summary:It is a fundamental goal of neuroscience to understand how feature-selective sensory response properties of cortical neurons emerge from the highly structured synaptic organization of the cortex. This thesis describes the receptive field (RF) organization in L2/3 of mouse primary visual cortex (V1) and the highly specific local circuits from which this organization emerges. We also examine how this connection specificity arises during development. We studied the organization of RFs in mouse V1 using in vivo two-photon calcium imaging. Local populations of neurons had a wide diversity of RFs, which were tightly clustered in visual space, with low scatter and high amounts of overlap. However, a retinotopic organization was observed and the ON and OFF subfields had non-random organization: more pairs of neurons had high subfield overlap, and more pairs of neurons had no subfield overlap, than would be expected by chance. ON subfields were more prevalent than OFF subfields and were more highly scattered in visual space. To relate this RF organization to the underlying neuronal circuitry, we used multiple whole-cell recordings in vitro to assess connections between neurons whose RFs had been mapped in vivo. The incidence and strength of connections were highly correlated with RF similarity. Neurons with spatially matched RFs (i.e. overlapping ON and OFF subfields) connected at high rates, with strong and often bidirectional connections, while neurons with mismatched RFs rarely connected with much weaker connections, despite covering similar regions of visual space. Although only a small fraction of neurons had matched RFs, these neurons formed the strongest connections. Thus, feature-specific information is provided by a small subset of connections that are sufficiently powerful to influence the stimulus selectivity of neuronal responses. To understand the development of functionally-specific connectivity, we performed similar experiments at different postnatal ages. Although responses were highly selective for visual features at eye-opening, neurons responding to similar features were not preferentially connected. After eye-opening, local connectivity reorganized extensively, such that more connections formed between neurons with similar response properties, and connections were lost between visually unresponsive neurons. This work provides insights into the organization of neocortical circuits, which can be used for biologically-informed computational models of the neocortex.