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Inhibitory pathways in the neocortical microcircuit

Abstract

Understanding how the canonical circuit implements computations requires that we characterize the components of the circuit and determine how they interact. Cortical components are often equated to the various classes of excitatory and inhibitory neuronal cell-types that occupy the six cortical layers. Excitatory cortical neurons are known to exhibit stereotyped, cell-type specific patterns of connectivity; these excitatory synaptic pathways are a central feature of cortical organization. It has been less clear whether inhibitory neurons are organized according to a similar logic. In this thesis I describe my efforts to map the inhibitory pathways of the neocortex, using the mouse primary somatosensory barrel cortex as a model.

In Chapter 1, I will give an introduction to theories of cortical function and general overview of the organization of cortical circuits. I will also provide a focused review of the inhibitory circuitry in layer 5 of the cortex. This chapter is presented, in part, in the form of reproductions of material from two reviews (one published and one in preparation) that I co-authored with my advisor. In Chapter 2, I describe the discovery of a novel disynaptic inhibitory pathway between layer 4 and layer 5 of the somatosensory cortex, and present evidence that this pathway contributes to selective sensory representations in layer 5. This work is presented as a published manuscript, which I co-authored with Dr. Scott Pluta. In Chapter 3, I describe a series of experiments probing the organization of two subnetworks of dendrite-targeting interneurons. These subnetworks exhibit complementary patterns of connectivity which enable them to differentially modulate the dynamics of cortical activity in a layer-specific manner. This work is presented as a first author manuscript (currently in review). Finally, in Chapter 4 I offer closing thoughts and directions for future work.

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