Dissecting the function of astrocytic synaptic cell adhesion molecules

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Information is transmitted through synapses in the nervous system. Efforts have been made to visualize synaptic connectivity and understand synapse formation. While essential synaptic molecules have mainly been studied in neurons, astrocytes also play a role in synapse interactions. Astrocytes express synaptic cell adhesion molecules (CAMs) like neuroligins (Nlgns), which could regulate astrocyte-neuron interactions. A recent study suggested that loss of astrocytic Nlgn2 affects astrocyte size and excitatory synaptogenesis, which conflicts with previous studies reporting that constitutive deletion of Nlgns does not affect synapse number. To investigate the role of astrocytic Nlgns, we genetically deleted Nlgns 1-3 in astrocytes and observed no impairment in synaptic protein expression or synapse number. Electrophysiological measurements and 3D astrocyte reconstruction showed no impact on synaptic function or astrocyte volume, respectively. Therefore, astrocytic Nlgns are not crucial for synaptogenesis or astrocyte morphogenesis. Further, monosynaptic rabies virus (RV) tracing methods have been developed to identify the molecules involved in synapse development. However, synapse number as measured by RV tracing does not always align with that as reported by traditional immunohistochemistry techniques. This discrepancy may be due to synaptic activity influencing RV tracing. Thus, we investigated whether RV tracing methods simply require structural synapses or if synaptic transmission is also necessary for neuronal labeling with RV. By eliminating evoked transmission, we found that spontaneous release is sufficient for RV spread. Loss of both evoked and spontaneous synaptic transmission halted retrograde labeling entirely. Our studies improve the understanding of astrocyte-mediated synapse maintenance and the techniques used to study them, supporting further research on the molecular and cellular aspects of synapses.


Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource.
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2023; ©2023
Publication date 2023; 2023
Issuance monographic
Language English


Author Golf, Samantha Rose
Degree supervisor Südhof, Thomas C
Thesis advisor Südhof, Thomas C
Thesis advisor Chen, Lu, (Professor of neurosurgery)
Thesis advisor Kaltschmidt, Julia
Thesis advisor Luo, Liqun, 1966-
Degree committee member Chen, Lu, (Professor of neurosurgery)
Degree committee member Kaltschmidt, Julia
Degree committee member Luo, Liqun, 1966-
Associated with Stanford University, School of Medicine
Associated with Stanford University, Neurosciences Program


Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Samantha Rose Golf.
Note Submitted to the Neurosciences Program.
Thesis Thesis Ph.D. Stanford University 2023.
Location https://purl.stanford.edu/zf430qh1976

Access conditions

© 2023 by Samantha Rose Golf
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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