Cable, Chloe2024-01-052024-01-052023-10https://hdl.handle.net/11299/259694University of Minnesota Ph.D. dissertation. October 2023. Major: Neuroscience. Advisor: Eric Newman. 1 computer file (PDF); vi, 90 pages.Retinal AII amacrine cells are extensively coupled together by electrical synapses. Changes to the strength of these synapses affect how signals are routed through rod and cone retinal pathways during scotopic and photopic vision. Plasticity at these electrical synapses have not, to date, been characterized using electrophysiological approaches. We investigated the effects of adenosine (AR) and N-methyl-D-aspartate receptor (NMDAR) activation on the electrical coupling between AII cells using dual whole-cell patch-clamp electrophysiology in mouse retinal slices. While neither AR activation nor inhibition affected junctional conductance, NMDAR activation substantially decreased junctional conductance between AII cells. Relieving the Mg2+ block of NMDARs through bath application of Mg2+-free solution or by depolarizing AII cells to 0 mV reduced junctional conductance. Exogenous application of NMDA decreased conductance between cells, a decrease which was blocked by the non-selective NMDAR antagonist APV but not by Ro 25-6981, a selective GluN2B-NMDAR antagonist. Addition of either D-serine or glycine, both NMDAR coagonists, without NMDA, reduced the junctional conductance and addition of either coagonist to NMDA-treated retinas further decreased conductance. Experiments were conducted in inositol 1,4,5-trisphosphate receptor type 2 KO and serine racemase KO mice and in WT mice with D-amino acid oxidase to reduce retinal D-serine levels. Under these conditions, the NMDA-mediated conductance decrease was maintained, indicating that D-serine is not necessary for NMDAR-mediated plasticity. These results demonstrate that NMDAR activation results in a decrease in electrical coupling between AII amacrine cells and suggests that both D-serine and glycine can serve as NMDAR coagonists for this plasticity.enAII Amacrine CellsDual Whole-Cell Patch-Clamp ElectrophysiologyElectrical SynapsesNMDA receptorsPlasticityRetinaThesis or Dissertation