TY  - JOUR
AU  - Oldani, Silvia
AU  - Moreno-Velasquez, Laura
AU  - Faiss, Lukas
AU  - Stumpf, Alexander
AU  - Rosenmund, Christian
AU  - Schmitz, Dietmar
AU  - Rost, Benjamin Rainer
TI  - SynaptoPAC, an optogenetic tool for induction of presynaptic plasticity
JO  - Journal of neurochemistry
VL  - 156
IS  - 3
SN  - 1471-4159
CY  - Oxford
PB  - Wiley-Blackwell
M1  - DZNE-2021-00053
SP  - 324 - 336
PY  - 2021
AB  - Optogenetic manipulations have transformed neuroscience in recent years. While sophisticated tools now exist for controlling the firing patterns of neurons, it remains challenging to optogenetically define the plasticity state of individual synapses. A variety of synapses in the mammalian brain express presynaptic long‐term potentiation (LTP) upon elevation of presynaptic cyclic adenosine monophosphate (cAMP), but the molecular expression mechanisms as well as the impact of presynaptic LTP on network activity and behavior are not fully understood. In order to establish optogenetic control of presynaptic cAMP levels and thereby presynaptic potentiation, we developed synaptoPAC, a presynaptically targeted version of the photoactivated adenylyl cyclase bPAC. In cultures of hippocampal granule cells of Wistar rats, activation of synaptoPAC with blue light increased action potential‐evoked transmission, an effect not seen in hippocampal cultures of non‐granule cells. In acute brain slices of C57BL/6N mice, synaptoPAC activation immediately triggered a strong presynaptic potentiation at mossy fiber synapses in CA3, but not at Schaffer collateral synapses in CA1. Following light‐triggered potentiation, mossy fiber transmission decreased within 20 min, but remained enhanced still after 30 min. The optogenetic potentiation altered the short‐term plasticity dynamics of release, reminiscent of presynaptic LTP. Our work establishes synaptoPAC as an optogenetic tool that enables acute light‐controlled potentiation of transmitter release at specific synapses in the brain, facilitating studies of the role of presynaptic potentiation in network function and animal behavior in an unprecedented manner.
KW  - Animals
KW  - Brain: physiology
KW  - Female
KW  - Long-Term Potentiation: physiology
KW  - Male
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Optogenetics: methods
KW  - Rats
KW  - Rats, Wistar
LB  - PUB:(DE-HGF)16
C6  - pmid:33037623
DO  - DOI:10.1111/jnc.15210
UR  - https://pub.dzne.de/record/154191
ER  -