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.
|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|
|Keywords:||Dendrites, Mouse, Optogenetics, Prefrontal cortex, Spines, Two-photon|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be