The role of Neuroligin-2 in fear circuits

Marth, Lena

dc.contributor.advisor	Krueger-Burg, Dilja Prof. Dr.
dc.contributor.author	Marth, Lena
dc.date.accessioned	2023-01-02T16:59:15Z
dc.date.available	2024-02-10T00:51:52Z
dc.date.issued	2023-01-02
dc.identifier.uri	http://resolver.sub.uni-goettingen.de/purl?ediss-11858/14435
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-9631
dc.format.extent	77 Seiten	de
dc.language.iso	deu	de
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/
dc.subject.ddc	610	de
dc.title	The role of Neuroligin-2 in fear circuits	de
dc.type	doctoralThesis	de
dc.contributor.referee	Krueger-Burg, Dilja Prof. Dr.
dc.date.examination	2023-02-07	de
dc.description.abstracteng	In the past decades, strong evidence arose that the emergence of a large variety of neuropsychiatric conditions is caused by perturbations of the synaptic transmission on the molecular level. The synapse is the key structure of neural networks since it enables neurons to communicate with others and to precisely coordinate their firing to generate a specific behavioral output. Due to its pivotal role in GABAergic transmission, the inhibitory synapse organizer Neuroligin-2 is a particularly interesting candidate potentially contributing to the emergence of neuropsychiatric conditions. In accordance with this notion, various mutations in NLGN2 gene have been associated with neuropsychiatric disorders such as autism spectrum disorder, schizophrenia and anxiety disorders. Transgenic mouse lines provide a valuable tool to study how perturbed Neuroligin-2 function is translated into deviant behavior. In this study, we sought to elucidate the circuit mechanisms underlying the impaired ability of global Neuroligin-2 knockout mice to retrieve fear memories in auditory cued fear conditioning, a well-established behavioral paradigm to investigate associative fear learning. To address this question, a combination of behavioral assessment and cFos immunohistochemistry was applied. Pursuing a top-bottom approach, we first identified changes in the activation pattern of several fear-related brain regions in Neuroligin-2 knockout mice. In particular, Neuroligin-2 knockout mice show altered activation patterns in the lateral amygdala and the auditory cortex, both of which were previously shown underlying plastic circuit rearrangements induced by temporal coincidence of the foot shock and the tone. Further, VIP-expressing neurons in both regions showed an aberrant activation pattern, indicating that their function might be altered by Neuroligin-2 deletion and making them a likely candidate to potentially contribute to the Neuroligin-2 phenotype in fear conditioning. Together, my findings shed a first light on the mechanistic underpinnings of the Neuroligin-2 knockout phenotype in fear conditioning, but also highlight the complexity of the implications of Neuroligin-2 in the fear circuit. Further, this work constitutes a fundament for subsequent experiments including local virus mediated Neuroligin-2 deletions as well as in vivo approaches such as deep-brain calcium imaging. In the long term, further research based on this work may succeed to identify potential targets for more specific drug treatment of fear-related disorders.	de
dc.contributor.coReferee	Bayer, Thomas A. Prof. Dr.
dc.subject.eng	fear conditioning	de
dc.subject.eng	Neuroligin-2	de
dc.subject.eng	Nlgn2	de
dc.subject.eng	fear circuit	de
dc.subject.eng	amygdala	de
dc.subject.eng	GABAergic neurons	de
dc.subject.eng	VIP	de
dc.subject.eng	mPFC	de
dc.subject.eng	PTSD	de
dc.subject.eng	Nlgn2 KO mice	de
dc.subject.eng	stereotactic surgeries	de
dc.subject.eng	behavior	de
dc.subject.eng	immunohistochemistry	de
dc.subject.eng	interneurons	de
dc.identifier.urn	urn:nbn:de:gbv:7-ediss-14435-3
dc.affiliation.institute	Medizinische Fakultät	de
dc.subject.gokfull	Medizin (PPN619874732)	de
dc.subject.gokfull	Psychiatrie (PPN619876344)	de
dc.description.embargoed	2024-02-10	de
dc.identifier.ppn	1830208705
dc.identifier.orcid	0000-0002-1158-0026	de
dc.notes.confirmationsent	Confirmation sent 2023-01-03T06:15:04	de

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Human- und Zahnmedizin [2871]

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