RT Journal Article
SR Electronic
T1 Glutamate release is inhibitory and unnecessary for the long-term potentiation of presynaptic function
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 099515
DO 10.1101/099515
A1 Zahid Padamsey
A1 Rudi Tong
A1 Nigel Emptage
YR 2017
UL http://biorxiv.org/content/early/2017/01/10/099515.abstract
AB Long-term potentiation (LTP) and long-term depression (LTD) of transmitter release probability (Pr) are thought to be triggered by the activation of glutamate receptors. Here, we demonstrate that glutamate release at CA3-CA1 synapses is in fact inhibitory and unnecessary for increases in Pr. Instead, at active presynaptic terminals, postsynaptic depolarization alone can increase Pr by promoting the release of nitric oxide from neuronal dendrites in a manner dependent on L-type voltage-gated Ca2+ channels. The release of glutamate, in contrast, decreases Pr by activating presynaptic NMDA receptors (NMDAR). Thus, net changes in Pr are determined by the combined effect of both LTP-promoting and LTD-promoting processes, that is, by the amount of glutamate release and postsynaptic depolarization that accompany presynaptic activity, respectively. Neither of these processes directly depends on the activation of postsynaptic NMDARs. We further show that presynaptic changes can be captured by a simple mathematical framework, in which the role of presynaptic plasticity is to ensure that the ability for a presynaptic terminal to release glutamate is matched with its ability to predict postsynaptic spiking.