Development and organization of hippocampal and neocortical circuits

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The function of the mature nervous system relies on patterns of connectivity established during development. Understanding the mechanisms that regulate the development of specific connections in the nervous system is a daunting task, yet is critical for our understanding of brain function and the underlying causes of neurodevelopmental disorders. In the first part of this dissertation, I use recently developed viral tracing techniques to examine connectivity patterns and their development in the neocortex. In the second part, I characterize the role of a transmembrane protein, Teneurin-3, in the development of topographic connections in the hippocampal region. The laminar organization of neocortical circuits has been studied in detail using a variety of techniques, including paired recordings and glutamate uncaging. Viral-genetic anatomical tracing techniques offer many complementary advantages to slice recordings and prior tracing tools. Here, we use rabies virus-based trans-synaptic tracing to map inputs to pyramidal neurons in different layers of the mouse neocortex. We combine rabies tracing with genetic analysis to examine the mechanisms that produce these wiring patterns, and show that the distribution of traced inputs is largely independent of NMDA receptor function in the recipient cells, suggesting a minimal role for activity-dependent refinement in shaping these connectivity patterns. Prior to activity-dependent refinement, axons are guided to appropriate target areas and cells by genetically encoded cues. Recent work has shown that members of the Teneurin family of transmembrane proteins play critical roles in instructing wiring specificity during development. I show that mouse Teneurin-3 is expressed specifically in topographically matched subregions of the hippocampal region, and is necessary for the proper arrangement of CA1 axonal projections to the subiculum. Finally, I describe tools we have generated to further dissect the function of Teneurin-3 in the development of these projections.


Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2016
Issuance monographic
Language English


Associated with Berns, Dominic Samuel
Associated with Stanford University, Neurosciences Program.
Primary advisor Luo, Liqun, 1966-
Thesis advisor Luo, Liqun, 1966-
Thesis advisor Hestrin, Shaul
Thesis advisor Shen, Kang, 1972-
Thesis advisor Südhof, Thomas C
Advisor Hestrin, Shaul
Advisor Shen, Kang, 1972-
Advisor Südhof, Thomas C


Genre Theses

Bibliographic information

Statement of responsibility Dominic Samuel Berns.
Note Submitted to the Program in Neurosciences.
Thesis Thesis (Ph.D.)--Stanford University, 2016.
Location electronic resource

Access conditions

© 2016 by Dominic Samuel Berns
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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