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The Role of Serotonin-cAMP Mediated Signaling in Drosophila Central Synaptic Transmission and its Implications in Larval Olfactory Associative Learning

Ganguly, Archan
http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1331263683

Abstract Details

2012, Doctor of Philosophy (PhD), Ohio University, Biological Sciences (Arts and Sciences).
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 Drosophila 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 Drosophila 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 GABAA-receptor response possibly through PKA mediated phosphorylation, thus resulting in an overall reduction of GABAergic synaptic transmission. This regulation of post-synaptic GABAA-receptors by cAMP is altered in the mushroom body (MB) neurons of cAMP mutants (e.g. dunce and rutabaga). 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 IPSC frequency. 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 Drosophila.
Daewoo Lee (Advisor)
Ralph DiCaprio, A (Committee Member)
Robert Colvin, A (Committee Member)
Jung Peter (Committee Member)
185 p.
Neurosciences
cAMP; synaptic plasticity; Drosophila larval learning; Serotonin; 5-HT7 receptor; Mushroom body

Recommended Citations

Citations

  • Ganguly, A. (2012). The Role of Serotonin-cAMP Mediated Signaling in Drosophila Central Synaptic Transmission and its Implications in Larval Olfactory Associative Learning [Doctoral dissertation, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1331263683

    APA Style (7th edition)

  • Ganguly, Archan. The Role of Serotonin-cAMP Mediated Signaling in Drosophila Central Synaptic Transmission and its Implications in Larval Olfactory Associative Learning. 2012. Ohio University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1331263683.

    MLA Style (8th edition)

  • Ganguly, Archan. "The Role of Serotonin-cAMP Mediated Signaling in Drosophila Central Synaptic Transmission and its Implications in Larval Olfactory Associative Learning." Doctoral dissertation, Ohio University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1331263683

    Chicago Manual of Style (17th edition)

ohiou1331263683
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© 2012, all rights reserved.
This open access ETD is published by Ohio University and OhioLINK.