Presynaptic neurotrophin-3 increases the number of tectal synapses, vesicle density, and number of docked vesicles in chick embryos.
To determine whether presynaptically derived neurotrophins may contribute to synaptic plasticity, we examined whether neurotrophin-3 (NT-3) changed the number, size, vesicle content, or vesicle distribution of synapses within the retinorecipient layers of the chick optic tectum. In this system, endogenous NT-3 derives presynaptically from retinal ganglion cell axons. Retinotectal synapses comprise the majority of synapses in superficial tectal layers, as demonstrated by destruction of retinotectal input by intraocular application of the drug monensin. To examine the effect of increased or decreased levels of NT-3, either exogenous NT-3 or monoclonal NT-3 blocking antibodies were injected into the optic tectum of 19-day-old chick embryos, spiked with radiolabeled protein to verify the success of injections and estimate effective concentrations. After 48 hours, the ultrastructure of superficial tectal layers was analyzed and compared with samples from control tecta injected with cytochrome C. NT-3 increased the number of synapses, synaptic vesicles/profile, synaptic vesicle densities, the number of docked vesicles, and the length of the synaptic profile. Deprivation of anterogradely transported endogenous NT-3 with NT-3 antibodies resulted in the opposite effect: decreased numbers of synapses, decreased vesicle densities, and decreased numbers of docked vesicles. Brain-derived neurotrophic factor (BDNF) had a largely different effect than NT-3. BDNF increased the density of vesicles and deprivation of endogenous TrkB ligands with TrkB fusion protein reduced the density of vesicles in the synapses, without effects on synapse number or docked vesicles. We conclude that anterogradely transported NT-3 affects synapse strength in a way that differs from that of presumably postsynaptic-derived BDNF.
Wang
Xiaoxia
X
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA.
Butowt
Rafal
R
von Bartheld
Christopher S
CS
D000818:Animals; D002642:Chick Embryo; D008854:Microscopy, Electron; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D020933:Neurotrophin 3 / Q000008:administration & dosage / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D013477:Superior Colliculi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*
D020933:Neurotrophin 3