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Dissection of Medial Prefrontal Cortex Circuitry and its Dopaminergic Modulation


The prefrontal cortex (PFC) is comprised of a network of excitatory and inhibitory neurons that are critical for a number of cognitive processes including the ability to make decisions. PFC dysfunction causes deficits in these domains and major aspects of psychiatric disorders. Notably, layer V of the PFC is thought to play an important role in regulating these higher order processes and contains heterogeneous subpopulations of pyramidal neurons with distinct morphologies and projections. Layer V of PFC is also the major site of dopaminergic modulation. However, unlike the striatum, where D1 or D2 receptors are known to differentially express in separate projection subtypes of medium spiny neurons, the distribution of D1 and D2Rs in layer V projection neurons within PFC is unclear. Notably, Dopamine D2 receptors (D2Rs) play major roles in both normal and pathological PFC function. Thus, knowing their expression and effects in layer V neurons can provide helpful insights into important mechanisms that underlie prefrontal activity, and ultimately cognitive function. Chapter 1 of this thesis examines the expression of D1Rs and D2Rs in layer V projection subtypes. We also describe a novel mechanism by which D2R activation can drastically enhance the excitability of a D2R-expressing layer V pyramidal subtype. In Chapter 2, we explore differences in how long range excitation and feedforward inhibition is processed in D2R-expressing and D2R-lacking layer V pyramidal neurons. We propose that these differences might confer these subtypes with separate computational properties important for normal PFC function.

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