Retinoic acid and neuroligin-2 : two molecular regulators of GABAergic synaptic transmission in postnatal somatosensory cortex
Abstract/Contents
- Abstract
- In the following thesis, I examine how two different molecular players shown to be critical during early neural development, retinoic acid and neuroligin-2, regulate GABAergic synaptic transmission in the postnatal brain. In chapter one, I explore how retinoic acid (RA) regulates GABAergic synaptic transmission in adult somatosensory cortex. As opposed to RA's crucial role in embryonic neural patterning, in recent years, using in vitro preparations, RA was discovered to mediate homeostatic synaptic plasticity in mature neurons of the hippocampus. In contrast to RARα's classic role as a transcriptional regulator, this ability to trigger homeostasis is conferred by a novel ability of retinoic acid receptor alpha (RARα) to regulate protein synthesis. Here, I conduct the first exploration as to whether retinoic acid also may regulate mature synaptic transmission in brain regions outside the hippocampus, in an acute brain slice preparation that may more closely preserve the in vivo circuitry than do cultured neuron preparations. I show that in contrast to its role in the hippocampus, in the somatosensory cortex, retinoic acid increases inhibitory synaptic transmission with no effects on excitation; that these effects appear to be mediated both pre- and postsynaptically; and that these effects seem limited to spontaneous, as opposed to evoked, transmission. Additionally, I examine the role of neuroligin-2 (NL2), a known regulator of early GABAergic synaptic development, in the mature somatosensory cortex. Using a recently developed conditional NL2 KO mouse, I establish that NL2 also plays a role in postnatal synapse development of the somatosensory cortex, and that consistent with studies from constitutive NL2 KOs, removal of NL2 results in decreased inhibitory transmission, including reduced evoked transmission from fast-spiking inhibitory neurons. I describe a series of attempts to rescue NL2 function at GABAergic synapses in vivo using chimeric proteins and domain deletions, in order to assess the "structure-function" of NL2 in vivo. I will discuss the technical and biological implications of both successful rescue and lack of rescue, both for NL biology and in terms of in vivo versus in vitro molecular approaches.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2016 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Yee, Ada Xin |
|---|---|
| Associated with | Stanford University, Neurosciences Program. |
| Primary advisor | Chen, Lu, (Professor of neurosurgery) |
| Thesis advisor | Chen, Lu, (Professor of neurosurgery) |
| Thesis advisor | Hestrin, Shaul |
| Thesis advisor | Malenka, Robert C |
| Thesis advisor | Shen, Kang, 1972- |
| Advisor | Hestrin, Shaul |
| Advisor | Malenka, Robert C |
| Advisor | Shen, Kang, 1972- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Ada Xin Yee. |
|---|---|
| Note | Submitted to the Program in Neurosciences. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Ada Yee
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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