Neuronal Pentraxins Mediate Silent Synapse Conversion in the Developing Visual System

Abstract

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 (ϽP10) 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 AMPARmediated 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.

Long Noncoding RNA-Directed Epigenetic Regulation of Gene Expression Is Associated With Anxiety-like Behavior in Mice

“…2F and G). The first of these, Gm21781, is upstream of a gene that encodes a DNA binding protein known as zinc finger and BTB domain containing 2 ( Zbtb2 ), which has been shown to be a potent epigenetic regulator (55), and the second, Gm11762, is antisense to neuronal pentraxin 1 ( Nptx1 ), which has been reported to enhance synaptogenesis and glutamate signalling through clustering of AMPA receptors (56). Finally, we observed a significant down-regulation of the neuropsychiatric disease-related lncRNA Gomafu in the mPFC, which occurred following fear conditioning but not after context exposure (Fig.…”

Refinement of the Retinogeniculate Synapse by Bouton Clustering

“…The use of ligand-activated Cre allowed us to control the number of cells labeled in the retina by titrating the dose of tamoxifen administered, and thus visualize single-cell morphology (Figure 1B-E). BD-RGC axon arbors target the area where we and others have previously characterized retinogeniculate synaptic refinement by slice electrophysiology (Chen and Regehr, 2000; Jaubert-Miazza et al, 2005; Koch and Ullian, 2010; Stevens et al, 2007). By focusing on one RGC subtype, structural heterogeneity arising from the existence of multiple RGC subtypes can be minimized.…”

Activity dependent mechanisms of visual map formation - From retinal waves to molecular regulators

“…Mutants of the immune system molecules, H2Db, have impaired LTD after patterned stimulation mimicking endogenous retinal waves [114]. Along similar lines, it was shown that neuronal pentraxins 1 and 2 (NP1/2) are required for the normal development of AMPAR-mediated transmission and could convert silent synapses during eye-specific refinement [115]. The discovery of all these immune system molecules that are regulated by activity has gained more weight and has also implied new players such as microglia and astrocytes in synaptic refinement.…”