Presynaptic neurotrophin‐3 increases the number of tectal synapses, vesicle density, and number of docked vesicles in chick embryos

Abstract

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.

Reciprocal Regulation of Presynaptic and Postsynaptic Proteins in Bipolar Spiral Ganglion Neurons by Neurotrophins

“…Recent studies attributed some of these antagonistic effects to neurotrophin uptake and processing in differing regions of the cell (Heerssen and Segal, 2002;Wang et al, 2003). In contrast, the experiments reported here, along with previous reports from our laboratory (Adamson et al, 2002a,b;Zhou et al, 2005) are not consistent with differential localization of neurotrophin support, because both BDNF and NT-3 are located within the peripheral hair cell receptors and both types of cognate receptors are found in the neurons.…”

“…Complementary and/or antagonistic effects of neurotrophins have been found to regulate growth, survival, and synapse morphology in different classes of neurons, which could vary during development (McAllister et al, 1997;Mou et al, 1998;Giehl et al, 2001;Wang et al, 2003). Recent studies attributed some of these antagonistic effects to neurotrophin uptake and processing in differing regions of the cell (Heerssen and Segal, 2002;Wang et al, 2003).…”

Cell-Autonomous TrkB Signaling in Presynaptic Retinal Ganglion Cells Mediates Axon Arbor Growth and Synapse Maturation during the Establishment of Retinotectal Synaptic Connectivity

“…Cerebellar inhibitory synapses are also modulated by BDNF, in which alterations in TrkB signaling in knock-out mice reduce the numbers of GABAergic boutons and synaptic specializations (Rico et al, 2002), and targeted deletion of the BDNF gene decreases the number of vesicles that are docked (Carter et al, 2002). In the chick visual system, alterations in BDNF levels within the target optic tectum also affect synaptic vesicle pool (Wang et al, 2003). Thus, a commonality between circuits and species is that synaptic vesicle numbers and densities are increased and synapses strengthened by enhanced BDNF signaling, and, conversely, synaptic vesicle numbers are reduced and synapses are weakened if BDNF signaling is impaired (Vicario-Abejon et al, 2002;Shen et al, 2006).…”

Synaptic Targeting of Retrogradely Transported Trophic Factors in Motoneurons: Comparison of Glial Cell Line-Derived Neurotrophic Factor, Brain-Derived Neurotrophic Factor, and Cardiotrophin-1 with Tetanus Toxin

“…Distinct fates of trophic factors responsible for survival only versus survival and synaptic plasticity Trophic factors such as BDNF and GDNF are known as "synaptotrophins" with significant effects on synaptic plasticity (Snider and Lichtman, 1996;Ribchester et al, 1998;Poo, 2001;Wang et al, 2002Wang et al, , 2003. For example, BDNF can strengthen synapses (Snider and Lichtman, 1996;Poo, 2001), and GDNF increases the release of acetylcholine (Liou et al, 1997;Ribchester et al, 1998) and dopamine (Hebert et al, 1996;Pothos et al, 1998;Bourque and Trudeau, 2000).…”