RT Journal Article
SR Electronic
T1 Biophysical demonstration of co-packaging of glutamate and GABA in individual synaptic vesicles in the central nervous system
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.23.436594
DO 10.1101/2021.03.23.436594
A1 SeulAh Kim
A1 Michael L. Wallace
A1 Mahmoud El-Rifai
A1 Alexa R. Knudsen
A1 Bernardo L. Sabatini
YR 2021
UL http://biorxiv.org/content/early/2021/03/23/2021.03.23.436594.abstract
AB Many mammalian neurons release multiple neurotransmitters to activate diverse classes of ionotropic receptors on their postsynaptic targets. Entopeduncular nucleus somatostatin (EP Sst+) neurons that project to the lateral habenula (LHb) release both glutamate and GABA, but it is unclear if these are packaged into the same or segregated pools of synaptic vesicles. Here we describe a novel method combining electrophysiology, spatially-patterned optogenetics, and computational modeling designed to analyze the mechanism of glutamate/GABA corelease. We find that the properties of PSCs elicited in LHb neurons by optogenetic activation of EP Sst+ terminals are only consistent with co-packaging of glutamate and GABA into individual vesicles. Furthermore, serotonin, which acts presynaptically to weaken EP Sst+ to LHb synapses, does so by altering the release probability of vesicles containing both transmitters. Our approach is broadly applicable to the study of multi-transmitter neurons throughout the brain and our results constrain mechanisms of neuromodulation in LHb.Competing Interest StatementThe authors have declared no competing interest.