Authors:	Venkataramanan, Anjana
Title:	Behavioural and Neuroanatomical Analysis of a Visual Working Memory in Drosophila melanogaster
Online publication date:	14-Jul-2020
Year of first publication:	2020
Language:	english
Abstract:	In my thesis, we could prove that the cyclic AMP-dependent Protein Kinase A (PKA), plays a critical role in the functioning of visual working memory in Drosophila melanogaster. The detour paradigm (Neuser et al., 2008, Nature) was used to assess the spatial orientation memory, which is built in the R3 ring neurons of the ellipsoid body (Kuntz et al. 2017, Curr. Biol.). Here, we show that this memory requires PKA activity specifically at the presynapse of the R3 neurons and that its availability at this location is negatively regulated by Rugose, which potentially sequesters PKA to the Golgi network of the R3 cell soma. When present at the presynapse, PKA phosphorylates Synapsin, the synaptic vesicle protein at the phosphorylation site-1. Interestingly, in some cases, this site-1 on Synapsin is edited by ADAR (Diegelmann et al., 2006, BMC Neurosci.), leading to an approximately equal proportion of edited and non-edited Synapsin. The unedited Synapsin is phosphorylated by PKA while the edited one is phosphorylated by Calcium-dependent Calmodulin Kinase II (CaMKII). The phosphorylation of Synapsin at site-1 leads to the deployment of synaptic vesicles filled with neurotransmitters from the reserve pool, thereby creating a shift between the reserve and the recyclable pool, potentially leading to the functioning of detour memory. Secondly, our work has revealed that although the visual working memory is built in the R3 neurons, additional neurons such as, the R2, R5 and R6 ring neurons along with the non-canonical ring neurons L-Ei and L-Em are also important for this memory. We also uncovered that the neurons governing the heading representation in Drosophila i.e., the E-PG and P-EN neurons also influence this working memory. We proved that the R3 and E-PG neurons have a bidirectional synaptic connectivity, which is stronger in one direction (E-PG to R3). We therefore predict that the idiothetic memory is built in the R3 neurons with the orientation information from the E-PG neurons and the visual input from the R2 neurons when the landmarks are present. Once the visual cues disappear, this memory is communicated either to the “executing neurons” which aid in its execution either independently, or via synaptic connections within the central complex. Additionally, with the help of deletion mutants of dTau and CRISPR/Cas9 variants of human Tau incorporated in place of the endogenous Drosophila Tau, we show that the absence of Tau activity accelerates the deficits in visual working memory in an age-dependent manner. We postulate that this was because of the potential slowing down of kinesin-mediated axonal transport of Amyloid Precursor Protein Like (APPL) in the aged Tau deletion mutants, as flAPPL is required for visual working memory in Drosophila (Rieche et al., 2018, Curr.Biol.).
DDC:	570 Biowissenschaften 570 Life sciences 590 Tiere (Zoologie) 590 Zoological sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 10 Biologie
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-4968
URN:	urn:nbn:de:hebis:77-openscience-c00bcf53-6864-4648-9454-0b6d957e4c948
Version:	Original work
Publication type:	Dissertation
License:	In Copyright
Information on rights of use:	https://rightsstatements.org/vocab/InC/1.0/
Extent:	IV, 251 Seiten
Appears in collections:	JGU-Publikationen