Developmental control of synaptic receptivity.
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.
Barker
Alison J
AJ
Department of Ophthalmology, University of California, San Francisco, San Francisco, California 94143-0730, USA.
Koch
Selina M
SM
Reed
Jamian
J
Barres
Ben A
BA
Ullian
Erik M
EM
D000818:Animals; D000831:Animals, Newborn; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*