Developmental Control of Synaptic Receptivity

Abstract

Are neurons born with the ability to form and receive synapses or do they acquire these abilities during development? We have previously found that purified postnatal retinal ganglion cells (RGCs) require soluble astrocyte-derived signals to form synapses in vitro and in vivo. Here we show that newly generated embryonic day 17 (E17) RGCs are able to form but not receive synapses under these conditions. Dendrite growth is not sufficient to trigger receptivity; rather, the ability of newly generated RGCs to receive synapses is acquired at E19 in response to direct contact by neighboring cell types. Direct contact with astrocytes, which are not present at E17 but are normally generated by E19, is sufficient to induce synaptic receptivity in E17 RGCs. In contrast, amacrine contact does not induce synaptic receptivity. Interestingly, astrocyte contact alters the localization of the synaptic adhesion molecule neurexin away from dendrites. In addition, dendritic expression of neurexin is sufficient to prevent astrocyte contact-mediated increases in synapse number, suggesting a molecular mechanism by which astrocyte contact regulates neuronal synaptic receptivity. Thus, synaptic receptivity is not induced simply by dendritic elaboration but must be signaled by both contact-mediated signaling from astrocytes and a shift in the dendritic localization of neurexin.

Morphine Modulation of Thrombospondin Levels in Astrocytes and Its Implications for Neurite Outgrowth and Synapse Formation

“…Control levels were about 8 puncta/neuron (Fig. 7B), which are comparable with values previously reported for retinal ganglion neurons that were also relatively immature and grown in heterochronic co-cultures with astrocytes (10,34). These density values also reflect the fact that counts of puncta are taken in a relatively thin plane at the center of the neuron, and z stacking of images would yield higher values.…”

“…Puncta per micrometer of dendrite was estimated using ImageJ software and custom plug-ins as described previously (34). To remove low frequency background from each image, the rolling ball background subtraction was applied.…”

“…TSP1 promotes neurite formation and adhesion in neurons (29 -32). Recently, a major breakthrough in astrocyte-neuron interactions occurred when TSP1/2 were shown to be important secretory astrocytic proteins that promote synapse formation in the developing brain (5,10,33,34). Both in vitro and in vivo evidence have been presented.…”

Protein Kinase Cϵ (PKCϵ) Promotes Synaptogenesis through Membrane Accumulation of the Postsynaptic Density Protein PSD-95

“…Punctate colocalization (clusters of proximal pre-and post-synaptic markers on neurites) of PSD-95 and synaptophysin is widely accepted as an indicator of synapses (43,44). Primary human neurons were treated with bryostatin 1or DCPLA-ME alone or after PKC⑀ KD for 10 days.…”

Integrins and Nitric Oxide in the Regulation of Glial Cells: Potential Roles in Pathological Pain

“…On the other hand, thrombospondisn interact with integrins, potentially supporting the adhesion of glial cells with neurons at the synapse. One investigation using embryonic retinal ganglion neurons has demonstrated that neurons are capable of forming, but not receiving, synapses unless physical contact with astrocytes had been established [79]. The integrin alphaVbeta3 on astrocytes has been shown to bind to a glycoprotein Thy-1 abundantly expressed on neurons [80].…”