Journal Article DZNE-2021-00053

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SynaptoPAC, an optogenetic tool for induction of presynaptic plasticity

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2021
Wiley-Blackwell Oxford

Journal of neurochemistry 156(3), 324 - 336 () [10.1111/jnc.15210]

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Abstract: 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.

Keyword(s): Animals (MeSH) ; Brain: physiology (MeSH) ; Female (MeSH) ; Long-Term Potentiation: physiology (MeSH) ; Male (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Optogenetics: methods (MeSH) ; Rats (MeSH) ; Rats, Wistar (MeSH)

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Contributing Institute(s):
  1. Network Dysfunction (AG Schmitz 1 ; AG Schmitz)
Research Program(s):
  1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2021
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Medline ; Creative Commons Attribution-NonCommercial CC BY-NC 4.0 ; OpenAccess ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; NationallizenzNationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2021-03-22, last modified 2023-09-15


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