Dissertation/Thesis Abstract

Input-specific organization of cellular and subcellular connectivity in superficial layers of the prefrontal cortex
by Little, Justin P., Ph.D., New York University, 2013, 190; 3602689
Abstract (Summary)

Discovering the rules of connectivity between neurons in the brain is a necessary step in the path to a complete understanding of neural function. Many of these connections are thought to be exquisitely organized into specific `circuits' at all levels of analysis: from macroscopic levels, between broadly distributed brains areas, to subcellular levels, within the dendritic trees of individual neurons. While in principle the components of the brain could interconnect randomly, theoretical and experimental work suggests that targeted connections, optimized for specific functions, could endow both individual and large networks of neurons with unique computational abilities. This specificity in circuit organization is likely to be especially important in the operations of brain areas like the prefrontal cortex (PFC) that mediate a diverse set of functions. In the first part of this Thesis, I describe a novel technique for mapping functional connections between brain regions at the level of individual connections onto the dendrites and dendritic spines of PFC pyramidal cells. Using a combination of optogenetics and two-photon microscopy, I show that inputs to the PFC from the amygdala, thalamus, hippocampus, and cortex each make specific connections with layer 2 PFC neurons. Furthermore, I demonstrate that this subcellular specificity influences the strength of this connection, and argue that functional connectivity in the PFC may be finely tuned in an input-specific manner. In the second part of this thesis, I investigate how synaptic and subcellular specificity in the targeting of inputs to the PFC may influence the behavior of larger circuits. In particular, I focus on a reciprocal circuit between the PFC and amygdala that is involved in emotional control. Using similar methods as in part one, I identify two distinct populations of PFC neurons that send segregated connections either to the amygdala or contralateral mPFC. These amygdala-projecting neurons receive preferentially strong excitatory connections from the amygdala itself. I then show that specificity at the level of synapses and subcellular targeting contributes to this difference, and could ultimately influence activity at level of long-range networks.

Indexing (document details)
Advisor: Carter, Adam G.
Commitee: Klann, Eric, Reyes, Alex, Sanes, Dan
School: New York University
Department: Center for Neural Science
School Location: United States -- New York
Source: DAI-B 75/03(E), Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Neurosciences
Keywords: Dendrites, Mouse, Optogenetics, Prefrontal cortex, Spines, Two-photon
Publication Number: 3602689
ISBN: 9781303559242
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