The Role of Serotonin-cAMP Mediated Signaling in <italic>Drosophila</italic> Central Synaptic Transmission and its Implications in Larval Olfactory Associative Learning
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ndltd-OhioLink-oai-etd.ohiolink.edu-ohiou13312636832021-08-03T05:47:17Z The Role of Serotonin-cAMP Mediated Signaling in <italic>Drosophila</italic> Central Synaptic Transmission and its Implications in Larval Olfactory Associative Learning Ganguly, Archan Neurosciences cAMP synaptic plasticity Drosophila larval learning Serotonin 5-HT7 receptor Mushroom body Changes in synaptic plasticity are thought to be the basis of information storage leading to memory formation. In both vertebrates and invertebrates, the cAMP signaling pathway has been shown to be critical for learning and memory. The combined use of advanced genetic tools and behavioral learning assays in <italic>Drosophila</italic> has helped define the role for cAMP signaling in olfactory associative learning. However, very little is known about how cAMP mediated changes in synaptic transmission, especially at central synapses, contribute to behavioral learning. In this thesis I have used a combination of electrophysiology on <italic>Drosophila</italic> primary neuronal cultures and behavioral larval learning assays to explore if cAMP mediated changes in synaptic plasticity can contribute to behavioral learning. I demonstrate that cAMP signaling activates PKA and thus leads to an increase in the frequency of excitatory cholinergic synaptic currents and a supression of inhibitory GABAergic synaptic currents. I also observe that cAMP modulates the inhibitory GABAergic synapses in two distinct ways. It increases pre-synaptic GABA release and also decreases post-synaptic GABA<sub>A</sub>-receptor response possibly through PKA mediated phosphorylation, thus resulting in an overall reduction of GABAergic synaptic transmission. This regulation of post-synaptic GABA<sub>A</sub>-receptors by cAMP is altered in the mushroom body (MB) neurons of cAMP mutants (e.g. <italic>dunce</italic> and <italic>rutabaga</italic>). These flies have physiologically opposite levels of cAMP and show defects in olfactory learning. I further demonstrate that a biogenic amine (5-HT) increases cholinergic EPSC frequency and decreases GABAergic IPSCfrequency. My work shows that 5-HT acts through the d5-HT7 receptor to activate cAMP-PKA signaling as its effect on cholinergic and GABAergic currents is similar to that observed with cAMP alone. I further note that the d5-HT7 receptor is expressed in the mushroom body neurons, which is critical for both olfactory appetitive and aversive learning. In summary, my work suggests that the d5-HT7 receptor in the MB, acting through the cAMP-PKA pathway, is as a key player in both the regulation of synaptic plasticity and olfactory associative learning in <italic>Drosophila</italic>. 2012-04-18 English text Ohio University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1331263683 http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1331263683 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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English |
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Neurosciences cAMP synaptic plasticity Drosophila larval learning Serotonin 5-HT7 receptor Mushroom body |
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Neurosciences cAMP synaptic plasticity Drosophila larval learning Serotonin 5-HT7 receptor Mushroom body Ganguly, Archan The Role of Serotonin-cAMP Mediated Signaling in <italic>Drosophila</italic> Central Synaptic Transmission and its Implications in Larval Olfactory Associative Learning |
author |
Ganguly, Archan |
author_facet |
Ganguly, Archan |
author_sort |
Ganguly, Archan |
title |
The Role of Serotonin-cAMP Mediated Signaling in <italic>Drosophila</italic> Central Synaptic Transmission and its Implications in Larval Olfactory Associative Learning |
title_short |
The Role of Serotonin-cAMP Mediated Signaling in <italic>Drosophila</italic> Central Synaptic Transmission and its Implications in Larval Olfactory Associative Learning |
title_full |
The Role of Serotonin-cAMP Mediated Signaling in <italic>Drosophila</italic> Central Synaptic Transmission and its Implications in Larval Olfactory Associative Learning |
title_fullStr |
The Role of Serotonin-cAMP Mediated Signaling in <italic>Drosophila</italic> Central Synaptic Transmission and its Implications in Larval Olfactory Associative Learning |
title_full_unstemmed |
The Role of Serotonin-cAMP Mediated Signaling in <italic>Drosophila</italic> Central Synaptic Transmission and its Implications in Larval Olfactory Associative Learning |
title_sort |
role of serotonin-camp mediated signaling in <italic>drosophila</italic> central synaptic transmission and its implications in larval olfactory associative learning |
publisher |
Ohio University / OhioLINK |
publishDate |
2012 |
url |
http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1331263683 |
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