eprintid: 28932
rev_number: 16
eprint_status: archive
userid: 5444
dir: disk0/00/02/89/32
datestamp: 2020-10-13 06:46:25
lastmod: 2020-10-20 09:21:51
status_changed: 2020-10-13 06:46:25
type: doctoralThesis
metadata_visibility: show
creators_name: Gärtig, Phil-Alan Ricardo
title: Synaptic patterns for reliable circuit function require postembryonic maintenance by Jeb-Alk and normal network activity during embryogenesis
subjects: ddc-500
subjects: ddc-570
divisions: i-140001
adv_faculty: af-11
keywords: Drosophila melanogaster, neuroscience, dendrites, synapses
abstract: A functioning nervous systems results from complex developmental processes. One requirement is that individual neurons need to form sufficient synaptic connections with adequate partners. Here, molecular signaling and neural activity control morphological development of axons and dendrites and synaptogenesis in order to establish and maintain stable networks. However, mechanisms maintaining stable postembryonic circuits are not well understood and the long-term effects of embryonic neural activity on neuronal morphology and connectivity are unkown. This thesis investigates trans-synaptic, anterograde Jelly-Belly-Anaplastic lymphoma kinase signaling in postembryonic circuit development and elucidates the establishment of synaptic patterns by embryonic neural activity in the motor circuit of Drosophila larva.
I demonstrate that Alk activity inhibits the formation of postsynaptic specializations on motoneurons during postembryonic circuit growth by analyzing single cell connectivity. I employ a new Bxb1 integrase-based technique for targeted mutations to show that presynaptic release site number of an upstream interneuron is unchanged but Jeb-Alk seems to elicit a negative feedback that limits the formation of presynaptic filopodia. These Jeb-Alk devoid circuits with altered synaptic patterns produce epilepsy-like seizure behavior. Additionally, in vivo time lapse imaging of dendrites reveals that dendritic growth and postsynaptic synaptogenesis are regulated independently and presynaptic filopodia likely promote dendritic elaboration. During embryogenesis, neural activity adjusts the establishment of synaptic patterns in motoneurons. In a picrotoxin-induced epilepsy-like model, dendritic growth is unaffected, but synaptic input is increased. The number of release sites of an upstream interneuron is again unaffected.
In summary, I identified cellular and molecular mechanisms required for the establishment and maintenance of synaptic patterns for reliable circuit function. With novel genetic and imaging techniques, I show embryonic neural activity is pivotal for the formation of functionally stable synaptic patterns, and establish Jeb-Alk signaling as a negative regulator of circuit expansion maintaining embryonically established connectivity. These developmental mechanisms highlight that balancing pre- and postsynaptic growth and synaptogenesis is central to stable network function.
date: 2020
id_scheme: DOI
id_number: 10.11588/heidok.00028932
ppn_swb: 1736014366
own_urn: urn:nbn:de:bsz:16-heidok-289328
date_accepted: 2020-09-18
advisor: HASH(0x559e37d78c10)
language: eng
bibsort: GARTIGPHILSYNAPTICPA2020
full_text_status: public
place_of_pub: Heidelberg
citation:   Gärtig, Phil-Alan Ricardo  (2020) Synaptic patterns for reliable circuit function require postembryonic maintenance by Jeb-Alk and normal network activity during embryogenesis.  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/28932/1/Thesis.pdf