Neuronal pentraxins mediate silent synapse conversion in the developing visual system.
Neuronal pentraxins (NPs) are hypothesized to play important roles in the recruitment of AMPA receptors (AMPARs) to immature synapses, yet a physiological role for NPs at nascent synapses in vivo has remained elusive. Here we report that the loss of NP1 and NP2 (NP1/2) leads to a dramatic and specific reduction in AMPAR-mediated transmission at developing visual system synapses. In thalamic slices taken from early postnatal mice (<P10) NP1/2 knock-out (KO) neurons displayed severely reduced AMPAR-mediated retinogeniculate transmission. The reduced currents reflected an increased number of silent synapses with no change in quantal amplitude or presynaptic release. These are the first data to demonstrate that NP1/2 are required in vivo for the normal development of AMPAR-mediated transmission. In addition, they suggest a novel role for NP1/2 in silent synapse conversion during a discrete developmental period when visual circuit connections are undergoing eye-specific refinement. After this period, retinogeniculate transmission not only recovered in the knock-outs but became excessive. The enhanced currents were attributable, at least in part, to a deficit in the characteristic elimination of functional inputs that occurs in the developing dLGN. These data indicate that the loss of NP1/2 disrupts several aspects of retinogeniculate development including the initial establishment of AMPAR transmission and the subsequent elimination of inappropriate circuit connections.
Koch
Selina M
SM
Department of Ophthalmology, University of California, San Francisco, San Francisco, California 94143, USA.
Ullian
Erik M
EM
D000818:Animals; D002097:C-Reactive Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005829:Geniculate Bodies / Q000254:growth & development / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000502:physiology; D018091:Receptors, AMPA / Q000378:metabolism; D012160:Retina / Q000254:growth & development / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013788:Thalamus / Q000254:growth & development* / Q000502:physiology; D014795:Visual Pathways / Q000254:growth & development* / Q000502:physiology; D000099153:Pentraxins
D002097:C-Reactive Protein; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D000099153:Pentraxins
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