Syed, Naweed I.McCamphill, Patrick2017-12-182017-12-182007McCamphill, P. (2007). Presynaptic modulation of a central cholinergic synapse by serotonin (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/1415http://hdl.handle.net/1880/102416Bibliography: p. 59-66Neuromodulation is central to all nervous system function, although the precise mechanisms by which neurotransmitters affect synaptic efficacy between central neurons remains to be fully elucidated. In this study, I examined the neuromodulatory action of serotonin (5-Hydroxytryptamine or 5-HT) at central synapses between identified neurons from the pond snail Lymnaea stagnalis. Using whole-cell voltage clamp and sharp electrode recording, I show that 5-HT strongly depresses synaptic strength between cultured, cholinergic neuron visceral dorsal 4 (VD4- Presynaptic) and its serotonergic partner left pedal dorsal 1 (LPeD 1 - postsynaptic ). This inhibition was accompanied by a decrease in synaptic depression, but had no effect on postsynaptic input resistance, indicating that it is of presynaptic origin. In addition, serotonin inhibited the presynaptic calcium current (lea) on a similar time course as the change in synaptic transmission. Inclusion of the non-hydrolysable GDP analoge, GDP-??-S, in the presynaptic pipette inhibited the serotonin mediated Ca2+ current depression, as did the membrane impermeable inactive cAMP analoge 80H-cAMP. A model depicting a negative feedback mechanism is presented, where serotonin either present in the extracellular milieu, or released from the postsynaptic cell may act back on the presynaptic cell to inhibit its voltage gated calcium channels through a G-protein coupled, cAMP-mediated second messenger system.viii, 66 leaves : ill. ; 30 cm.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.master thesis10.11575/PRISM/1415