Stability, affinity, and chromatic variants of the glutamate sensor iGluSnFR

Marvin, Jonathan S; Scholl, Benjamin; Wilson, Dana E.; Podgorski, Kaspar; Kazemipour, Abbas; Müller, Johannes Alexander; Schoch, Susanne; Quiroz, Francisco José Urra; Rebola, Nelson; Bao, Huan; Little, Justin P.; Tkachuk, Ariana N.; Cai, Edward; Hantman, Adam W.; Wang, Samuel S.‐H.; DePiero, Victor J.; Borghuis, Bart G.; Chapman, Edwin R.; Dietrich, Dirk; DiGregorio, David A.; Fitzpatrick, David; Looger, Loren L.

doi:10.1038/s41592-018-0171-3

Cited by 355 publications

(356 citation statements)

References 29 publications

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“…In this study, we took advantage of the recently developed, genetically encoded optical iGluSnFR sensors for glutamate [19,24], in an attempt to detect changes in glutamate release following the induction of LTP. We have successfully transduced the sensors in hippocampal Schaffer collateral fibres using neonatal viral infection.…”

Section: Discussionmentioning

confidence: 99%

“…We employed the new generation of AAV-based sensor variant with a relatively high off-rate, AAV9.hSynap.i-GluSnFR.WPRE.SV40, but also used the recently described low off-rate sensor variant, SF-iGluSnFR.A184S [24] for comparison. Although AAV9 appeared to penetrate more readily after ICV administration [25] than did AAV2/1, at three to 4 weeks post-injection, both methods provided efficient labelling of Schaffer collateral fragments in S. radiatum ( Fig.…”

Section: Viral Delivery Of Iglusnfr In Neonates For Multi-synapse Glumentioning

confidence: 99%

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Optical monitoring of glutamate release at multiple synapses in situ detects changes following LTP induction

2020

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Information processing and memory formation in the brain relies on release of the main excitatory neurotransmitter glutamate from presynaptic axonal specialisations. The classical Hebbian paradigm of synaptic memory, long-term potentiation (LTP) of transmission, has been widely associated with an increase in the postsynaptic receptor current.Whether and to what degree LTP induction also enhances presynaptic glutamate release has been the subject of debate. Here, we took advantage of the recently developed genetically encoded optical sensors of glutamate (iGluSnFR) to monitor its release at CA3-CA1 synapses in acute hippocampal slices, before and after the induction of LTP. We attempted to trace release events at multiple synapses simultaneously, by using two-photon excitation imaging in fast frame-scanning mode. We thus detected a significant increase in the average iGluSnFR signal during potentiation, which lasted for up to 90 min. This increase may reflect an increased amount of released glutamate or, alternatively, reduced glutamate binding to high-affinity glutamate transporters that compete with iGluSnFR.

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Section: Discussionmentioning

confidence: 99%

Section: Viral Delivery Of Iglusnfr In Neonates For Multi-synapse Glumentioning

confidence: 99%

Optical monitoring of glutamate release at multiple synapses in situ detects changes following LTP induction

2020

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“…It remains to be determined whether KIN-4, MEC-2, and DGK-1 are involved in the regulation of such ion channels to impact on the release of neurotransmitter from AFD. Utilization of the recently developed optical sensors for neurotransmitters (57)(58)(59)(60) would unveil the dynamics of axonal computations and help dissect the mechanisms by which kin-4, mec-2, and dgk-1 regulate the release of either or both of glutamate and neuropeptide from the AFD neuron.…”

Section: Discussionmentioning

confidence: 99%

Presynaptic MAST kinase controls opposing postsynaptic responses to convey stimulus valence in Caenorhabditis elegans

Nakano

Ikeda

Tsukada

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Presynaptic plasticity is known to modulate the strength of synaptic transmission. However, it remains unknown whether regulation in presynaptic neurons can evoke excitatory and inhibitory postsynaptic responses. We report here that the Caenorhabditis elegans homologs of MAST kinase, Stomatin, and Diacylglycerol kinase act in a thermosensory neuron to elicit in its postsynaptic neuron an excitatory or inhibitory response that correlates with the valence of thermal stimuli. By monitoring neural activity of the valence-coding interneuron in freely behaving animals, we show that the alteration between excitatory and inhibitory responses of the interneuron is mediated by controlling the balance of two opposing signals released from the presynaptic neuron. These alternative transmissions further generate opposing behavioral outputs necessary for the navigation on thermal gradients. Our findings suggest that valence-encoding interneuronal activity is determined by a presynaptic mechanism whereby MAST kinase, Stomatin, and Diacylglycerol kinase influence presynaptic outputs.

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“…Thus far, VTA VGluT2 neurons appear to have diverse roles in motivated behavior 25,26 . Here, by using genetically encoded fluorescent reporters of glutamate and GABA signaling [31][32][33] , we aimed to identify how diverse rewarding and aversive information is neurochemically communicated to VTA VGluT2 neurons during motivated behavior.…”

Section: Discussionmentioning

confidence: 99%

Neurochemical signaling of reward and aversion by ventral tegmental area glutamate neurons

McGovern¹,

Polter

Root³

2020

Preprint

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behaviors, our electrophysiological recordings indicated that glutamate input primarily regulates the spontaneous firing of these neurons. Together, these results 1) provide new neurochemical insights into how VTA VGluT2 neurons integrate multiple neurotransmitters during reward and aversion, and 2) suggest that glutamate is the primary regulator of VTA VGluT2 neuron activity and contributes to the diversity in signaling of reward and aversion by these neurons.

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Stability, affinity, and chromatic variants of the glutamate sensor iGluSnFR

Cited by 355 publications

References 29 publications

Optical monitoring of glutamate release at multiple synapses in situ detects changes following LTP induction

Optical monitoring of glutamate release at multiple synapses in situ detects changes following LTP induction

Presynaptic MAST kinase controls opposing postsynaptic responses to convey stimulus valence in Caenorhabditis elegans

Neurochemical signaling of reward and aversion by ventral tegmental area glutamate neurons

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