Understanding the Microcircuits in Monkey Sensory Cortices: a Connectomic Approach

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Abstract The development of serial confocal and electron-microscopy (EM), and automated image segmentation have allowed us to elucidate some of the structural details of the cortical circuit at the cellular and synaptic level. This information is critical because there is a close link between the morphological properties of circuits in different brain areas and their function. It is broadly accepted that the canonical microcircuit of the cortex is a repeating motif across cortex. Once the structure and function in the local motif is understood this could be applied across all of cortex. However, recently it has been shown that there are major laminar, areal and species differences that need to be taken into account by this model. Another important feature of the canonical circuit in sensory areas is that the initial thalamocortical (TC) driving input to layer 4 in cortex, which was presumed to be weak, needs to be massively amplified to obtain the observed rates of spiking. However, recent studies have shown that the weak TC assumption, has underestimated the TC strength by 2-4 times. I hypothesis that, although the canonical circuit may provide general framework for cortical circuit functioning, diverse sensory brain areas have major laminar differences in their neuronal and synaptic distributions. These differences will, in turn, reflect the diverse processing roles and capabilities of the brain areas. To test this hypothesis I will examine three primary sensory areas in macaque monkey cortex using Focused Ion Beam/Scanning EM to determine detailed synaptic connectivity, using high-resolution confocal microscopy to provide large scale determination of specific synaptic connectivity, and using mid- resolution confocal microscopy to determine global cell type distributions in specific brain regions. If, as I hypothesize, there are major quantitative differences between areas that will reflect their diverse processing roles and capabilities, this will call for a refinement of the concept of the canonical circuit. These quantitative results are important to build realistic population based spiking models of cortex that can reproduce many of the detailed functional characteristics that are found in the brain. They are also important because understanding the basic cortical organization of the normal brain is essential, as it provides the standard against which it can be judged which processes can be seen to be altered or damaged in disorders that affect the cerebral cortex. Additionally, an important part of this project is my professional development as a PI. As such, I have established a research enhancement plan to increase my research scholarship and publications, with the final goal of acquiring non-SCORE research support.