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000154191 0247_ $$2doi$$a10.1111/jnc.15210
000154191 0247_ $$2ISSN$$a0022-3042
000154191 0247_ $$2ISSN$$a1471-4159
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000154191 037__ $$aDZNE-2021-00053
000154191 041__ $$aEnglish
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000154191 1001_ $$0P:(DE-2719)2812467$$aOldani, Silvia$$b0$$eFirst author$$udzne
000154191 245__ $$aSynaptoPAC, an optogenetic tool for induction of presynaptic plasticity
000154191 260__ $$aOxford$$bWiley-Blackwell$$c2021
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000154191 520__ $$aOptogenetic 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.
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000154191 650_2 $$2MeSH$$aAnimals
000154191 650_2 $$2MeSH$$aBrain: physiology
000154191 650_2 $$2MeSH$$aFemale
000154191 650_2 $$2MeSH$$aLong-Term Potentiation: physiology
000154191 650_2 $$2MeSH$$aMale
000154191 650_2 $$2MeSH$$aMice
000154191 650_2 $$2MeSH$$aMice, Inbred C57BL
000154191 650_2 $$2MeSH$$aOptogenetics: methods
000154191 650_2 $$2MeSH$$aRats
000154191 650_2 $$2MeSH$$aRats, Wistar
000154191 7001_ $$00000-0001-9735-0039$$aMoreno-Velasquez, Laura$$b1
000154191 7001_ $$0P:(DE-2719)9001061$$aFaiss, Lukas$$b2$$udzne
000154191 7001_ $$00000-0002-1510-6970$$aStumpf, Alexander$$b3
000154191 7001_ $$00000-0002-3905-2444$$aRosenmund, Christian$$b4
000154191 7001_ $$0P:(DE-2719)2810725$$aSchmitz, Dietmar$$b5$$eCorresponding author$$udzne
000154191 7001_ $$0P:(DE-2719)2810914$$aRost, Benjamin Rainer$$b6$$eLast author$$udzne
000154191 773__ $$0PERI:(DE-600)2020528-4$$a10.1111/jnc.15210$$gVol. 156, no. 3, p. 324 - 336$$n3$$p324 - 336$$tJournal of neurochemistry$$v156$$x1471-4159$$y2021
000154191 8564_ $$uhttps://onlinelibrary.wiley.com/doi/10.1111/jnc.15210
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