Postsynaptic and Presynaptic NMDARs Have Distinct Roles in Visual Circuit Development

• Published in: Cell reports (Cambridge) Vol. 32; no. 4; p. 107955
• Main Authors: Kesner, Philip, Schohl, Anne, Warren, Elodie C., Ma, Fan, Ruthazer, Edward S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.07.2020; Elsevier
• Subjects: Animals; axon; Axons - metabolism; dendrite; Dendrites - metabolism; Embryo, Nonmammalian; Morpholino oligonucleotide; Morpholinos - genetics; Morpholinos - pharmacology; Neurogenesis; Presynaptic Terminals - metabolism; receptive field; Receptors, N-Methyl-D-Aspartate - metabolism; Receptors, N-Methyl-D-Aspartate - physiology; Retina - metabolism; Retinal Ganglion Cells - metabolism; retinotectal; synapse; Synapses - metabolism; two-photon microscopy; visual system; whole-cell electrophysiology; Xenopus; Xenopus laevis - metabolism; Xenopus; visual system; receptive field; retinotectal; two-photon microscopy; Morpholino oligonucleotide; dendrite; whole-cell electrophysiology; synapse; axon
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.107955

To study contributions of N-methyl-D-aspartate receptors (NMDARs) in presynaptic and postsynaptic neurons of the developing visual system, we microinject antisense Morpholino oligonucleotide (MO) against GluN1 into one cell of two-cell-stage Xenopus laevis embryos. The resulting bilateral segregation of MO induces postsynaptic NMDAR (postNMDAR) knockdown in tectal neurons on one side and presynaptic NMDAR (preNMDAR) knockdown in ganglion cells projecting to the other side. PostNMDAR knockdown reduces evoked NMDAR- and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated retinotectal currents. Although the frequency of spontaneous synaptic events is increased, the probability of evoked release is reduced. PreNMDAR knockdown results in larger evoked and unitary synaptic responses. Structurally, postNMDAR and preNMDAR knockdown produce complementary effects. Axonal arbor complexity is reduced by preNMDAR-MO and increased by postNMDAR-MO, whereas tectal dendritic arbors exhibit the inverse. The current study illustrates distinct roles for pre- and postNMDARs in circuit development and reveals extensive transsynaptic regulation of form and function. [Display omitted] •Presynaptic release properties are modulated by NMDARs on postsynaptic neurons•Postsynaptic response amplitudes are influenced by NMDARs on presynaptic neurons•NMDARs on post- and presynaptic neurons impact neuronal morphology in opposing ways•NMDAR knockdown leads to abnormalities in visual input convergence NMDA receptors play central roles in developmental plasticity, but their diversity of contributions to circuit refinement has not been fully explored. Here, Kesner et al. reveal distinct roles of NMDA receptors on pre- and postsynaptic neurons in visual circuit development, including an unexpected degree of transsynaptic functional and structural regulation.