AMPA receptors regulate experience-dependent dendritic arbor growth in vivo.
The size and shape of neuronal dendritic arbors affect the number and type of synaptic inputs, as well as the complexity and function of brain circuits. In the intact brain, dendritic arbor growth and the development of excitatory glutamatergic synapse are concurrent. Consequently, it has been difficult to resolve whether synaptic inputs drive dendritic arbor development. Here, we test the role of AMPA receptor (AMPAR)-mediated glutamatergic transmission in dendrite growth by expressing peptides corresponding to the intracellular C-terminal domains of AMPAR subunits GluR1 (GluR1Ct) and GluR2 (GluR2Ct) in optic tectal neurons of the Xenopus retinotectal system. These peptides significantly reduce AMPAR synaptic transmission in transfected neurons while leaving visual system circuitry intact. Daily in vivo imaging over 5 days revealed that GluR1Ct or GluR2Ct expression dramatically impaired dendrite growth, resulting in less complex arbors than controls. Time-lapse images collected at 2-h intervals over 6 h show that both GluR1Ct and GluR2Ct decrease branch lifetimes. Ultrastructural analysis indicates that synapses formed onto neurons expressing the GluRCt are less mature than synapses onto control neurons. These data suggest that the failure to form complex arbors is due to reduced stabilization of new synapses and dendritic branches. Although visual stimulation increases dendritic arbor growth rates in control tectal neurons, a weak postsynaptic response to visual experience in GluRCt-expressing cells leads to retraction of branches. These results indicate that AMPAR-mediated transmission underlies experience-dependent dendritic arbor growth by stabilizing branches, and support a competition-based model for dendrite growth.
Haas
Kurt
K
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Li
Jianli
J
Cline
Hollis T
HT
D000818:Animals; D003712:Dendrites / Q000378:metabolism / Q000502:physiology*; D004594:Electrophysiology; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D018091:Receptors, AMPA / Q000502:physiology*; D017470:Receptors, Glutamate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission; D013997:Time Factors; D014982:Xenopus laevis
D010455:Peptides; D018091:Receptors, AMPA; D017470:Receptors, Glutamate