TY - JOUR
T1 - Post-tetanic potentiation lowers the energy barrier for synaptic vesicle fusion independently of synaptotagmin-1
AU - Huson, Vincent
AU - Meijer, Marieke
AU - Dekker, Rien
AU - Veer, Mirelle Ter
AU - Ruiter, Marvin
AU - van Weering, Jan
AU - Verhage, Matthijs
AU - Cornelisse, L. Niels
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Previously, we showed that modulation of the energy barrier for synaptic vesicle fusion boosts release rates supralinearly (Schotten, 2015). Here we show that mouse hippocampal synapses employ this principle to trigger Ca2+-dependent vesicle release and post-tetanic potentiation (PTP). We assess energy barrier changes by fitting release kinetics in response to hypertonic sucrose. Mimicking activation of the C2A domain of the Ca2+-sensor Synaptotagmin-1 (Syt1), by adding a positive charge (Syt1D232N) or increasing its hydrophobicity (Syt14W), lowers the energy barrier. Removing Syt1 or impairing its release inhibitory function (Syt19Pro) increases spontaneous release without affecting the fusion barrier. Both phorbol esters and tetanic stimulation potentiate synaptic strength, and lower the energy barrier equally well in the presence and absence of Syt1. We propose a model where tetanic stimulation activates Syt1-independent mechanisms that lower the energy barrier and act additively with Syt1-dependent mechanisms to produce PTP by exerting multiplicative effects on release rates.
AB - Previously, we showed that modulation of the energy barrier for synaptic vesicle fusion boosts release rates supralinearly (Schotten, 2015). Here we show that mouse hippocampal synapses employ this principle to trigger Ca2+-dependent vesicle release and post-tetanic potentiation (PTP). We assess energy barrier changes by fitting release kinetics in response to hypertonic sucrose. Mimicking activation of the C2A domain of the Ca2+-sensor Synaptotagmin-1 (Syt1), by adding a positive charge (Syt1D232N) or increasing its hydrophobicity (Syt14W), lowers the energy barrier. Removing Syt1 or impairing its release inhibitory function (Syt19Pro) increases spontaneous release without affecting the fusion barrier. Both phorbol esters and tetanic stimulation potentiate synaptic strength, and lower the energy barrier equally well in the presence and absence of Syt1. We propose a model where tetanic stimulation activates Syt1-independent mechanisms that lower the energy barrier and act additively with Syt1-dependent mechanisms to produce PTP by exerting multiplicative effects on release rates.
UR - http://www.scopus.com/inward/record.url?scp=85090636669&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85090636669&partnerID=8YFLogxK
U2 - https://doi.org/10.7554/ELIFE.55713
DO - https://doi.org/10.7554/ELIFE.55713
M3 - Article
C2 - 32831174
SN - 2050-084X
VL - 9
SP - 1
EP - 56
JO - eLife
JF - eLife
M1 - e55713
ER -