A modulatory role for the NMDA receptor glycine binding site during fictive locomotion in Xenopus laevis larvae
Year: 2012
Type: dissertation
Abstract: This thesis follows up previous work carried out investigating the role of the NMDA receptor \nglycine site in fictive swimming in Xenopus laevis tadpole larvae. Extracellular glycine has \nbeen assumed to be present in the synaptic cleft at saturating levels, leaving no vacant NMDA \nglycine binding sites. D-serine, a ligand at the NMDA glycine binding site, has been found to \nincrease the level of excitation in the CPG, increasing episode duration, increasing the \noccurrence of spontaneously occurring episodes, and producing more variation in burst \nfrequency and amplitude within swim episodes leading to a waxing and waning pattern of \nswimming. These effects are also seen when glycine is co-applied with strychnine, and when \nglycinergic uptake is inhibited by the transporter blocker ALX. In this work, these findings \nhave been confirmed and examined further by means of whole cell patch clamp recordings of \nspinal neurons of the CPG. D-serine causes a reversible increase in tonic depolarisation of \nspinal neurons along with a reversible decrease in spike height and an increase in spike \nfrequency. D-serine also produces a paradoxical decrease in the membrane conductance and \nproduces the above mentioned waxing and waning of swim episodes during which the \nneurons fire more or less intensely along with the waxing and waning. Furthermore, in the \npresence of TTX, bicuculline, and strychnine, D-serine increases the occurrence of miniature \nexcitatory postsynaptic potentials. All of the above mentioned effects could be partially or \nfully reversed by either the NMDA receptor antagonist D-AP5 or the NMDA glycine binding \nsite antagonist L-689560. In addition, D-serine could enhance NMDA-dependent intrinsic \nmembrane potential oscillations, and in some experiments produce oscillations of a frequency \nreminiscent of oscillations dually dependent on NMDA and 5-HT. In conclusion, this work \nhas shown that there are vacant glycine binding sites on NMDA receptors that can be bound \nby D-serine leading to an increase in overall excitation in the CPG. This is most likely \nachieved by tonic activation of NMDA receptors that is masked until the glycine site is \noccupied.
Author: E. Rebecka Björnfors
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funder: Strong
OpenAlex ID: W563229338