Opto-vTrap, an optogenetic trap for reversible inhibition of vesicular release, synaptic transmission, and behavior

Won, Joungha; Pankratov, Yuriy; Jang, Minwoo Wendy; Kim, Sunpil; Ju, Yeon Ha; Lee, Sangkyu; Lee, Seung Eun; Kim, Arie; Park, Soowon; Lee, C. Justin; Heo, Won Do

doi:10.1016/j.neuron.2021.11.003

Cited by 12 publications

(15 citation statements)

References 57 publications

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“…Astrocytes are the most abundant cell types in the brain and play a vital role in both physiological [ 6 – 8 ] and pathological [ 9 – 13 ] conditions. The astrocytic Ca 2+ signaling is critically involved in various gliotransmitter releases such as glutamate [ 14 ], GABA [ 15 ], ATP [ 16 ], and d -serine [ 17 ], which are critical for glia-neuron communication.…”

Section: Introductionmentioning

confidence: 99%

Dopamine-induced astrocytic Ca2+ signaling in mPFC is mediated by MAO-B in young mice, but by dopamine receptors in adult mice

et al. 2022

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Dopamine (DA) plays a vital role in brain physiology and pathology such as learning and memory, motor control, neurological diseases, and psychiatric diseases. In neurons, it has been well established that DA increases or decreases intracellular cyclic AMP (cAMP) through D1-like or D2-like dopamine receptors, respectively. In contrast, it has been elusive how astrocytes respond to DA via Ca2+ signaling and regulate synaptic transmission and reward systems. Previous studies suggest various molecular targets such as MAO-B, D1R, or D1R–D2R heteromer to modulate astrocytic Ca2+ signaling. However, which molecular target is utilized under what physiological condition remains unclear. Here, we show that DA-induced astrocytic Ca2+ signaling pathway switches during development: MAO-B is the major player at a young age (5–6 weeks), whereas DA receptors (DARs) are responsible for the adult period (8–12 weeks). DA-mediated Ca2+ response in the adult period was decreased by either D1R or D2R blockers, which are primarily known for cyclic AMP signaling (Gs and Gi pathway, respectively), suggesting that this Ca2+ response might be mediated through Gq pathway by D1R–D2R heterodimer. Moreover, DAR-mediated Ca2+ response was not blocked by TTX, implying that this response is not a secondary response caused by neuronal activation. Our study proposes an age-specific molecular target of DA-induced astrocytic Ca2+ signaling: MAO-B in young mice and DAR in adult mice.

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Section: Introductionmentioning

confidence: 99%

Dopamine-induced astrocytic Ca2+ signaling in mPFC is mediated by MAO-B in young mice, but by dopamine receptors in adult mice

et al. 2022

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“…We fused CIB1, tagged with GFP, to SNG-1 and expressed an mOrange2-tagged CRY2olig(535) in the cytosol of neurons. Our design resembled the recently reported opto-vTrap 36 . We hypothesized that blue light illumination (470 nm) should activate the PHR domain of CRY2 (Ref.…”

Section: Development Of Optosync An Optogenetic Tool For Clustering O...mentioning

confidence: 56%

“…The recently developed opto-vTrap 36 , which is based on a LARIAT approach 35 , utilizes heterodimerization of CRY2 with CIB1 31,32 . We tried a similar approach expressing soluble CRY2 in synapses, and targeted CIBN to SV membranes via SNG-1.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies utilized CRY2 heteromerization to trap target proteins into complexes using light 35 . This 'light-activated reversible inhibition by assembled trap' (LARIAT) was recently used to interfere with synaptic transmission by targeting VAMP2 36 . These authors suggested that their approach inhibits synaptic transmission by blocking the SV release machinery, i.e.…”

Section: Introductionmentioning

confidence: 99%

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Rapid and reversible optogenetic silencing of synaptic transmission by clustering of synaptic vesicles

Vettkoetter

Schneider

Liewald

et al. 2022

Preprint

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Silencing neurons acutely and specifically informs about their functional roles in circuits and behavior. Existing optogenetic silencers include ion pumps or channels, and tools that damage the neurotransmitter release machinery. While the former hyperpolarize the cell and can alter ionic gradients, the latter allow only slow recovery, requiring de novo synthesis. Thus, there is a need for other strategies combining fast activation and reversibility. Here, we use light-evoked homo-oligomerization of cryptochrome CRY2 to silence synaptic transmission, by clustering synaptic vesicles (SVs). We benchmark this tool, optoSynC, by electrophysiology and locomotion in Caenorhabditis elegans. optoSynC clusters SVs within 25 s, causing approximation, observable by electron microscopy. Locomotion silencing is rapid (tau on ~15 s) and recovers quickly (tau off ~10 min) after light-off. Further, optoSynC can inhibit exocytosis for several hours, at very low light intensities. optoSynC is a highly efficient, "non-ionic" optogenetic silencer that may further allow to manipulate different SV pools.

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“…Astrocytes are the most abundant cell types in the brain and play a vital role in both physiological [6,7,8] and pathological [9,10,11,12,13] conditions. The astrocytic Ca 2+ signaling is critically involved in various gliotransmitter releases such as glutamate [14], GABA [15], ATP [16], and D-serine [17], which are critical for glia-neuron communication.…”

Section: Introductionmentioning

confidence: 99%

Dopamine-induced astrocytic Ca2+ signaling in mPFC is mediated by MAO-B in young mice, but by dopamine receptors in adult mice

Kim¹,

Kwon

Park³

et al. 2022

Preprint

Self Cite

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Dopamine (DA) plays a vital role in brain physiology and pathology such as learning and memory, motor control, neurological diseases, and psychiatric diseases. In neurons, it has been well established that DA increases or decreases intracellular cyclic AMP (cAMP) through D1-like or D2-like dopamine receptors, respectively. In contrast, astrocytes respond to DA via Ca2+ signaling and regulate synaptic transmission and reward systems. Previous studies suggest various molecular targets such as MAO-B, D1R, or D1R-D2R heteromer to modulate astrocytic Ca2+ signaling. However, which molecular target is utilized under what physiological condition remains unclear. Here, we show that DA-induced astrocytic Ca2+ signaling pathway switches during development: MAO-B is the major player at a young age (5 - 6 weeks), whereas DA receptors (DARs) are responsible for the adult period (8 - 12 weeks). DA-mediated Ca2+ response in the adult period was decreased by either D1R or D2R blockers, which are primarily known for cyclic AMP signaling (Gs and Gi pathway, respectively), suggesting that this Ca2+ response might be mediated through Gq pathway by D1R-D2R heterodimer. Moreover, DAR-mediated Ca2+ response was not blocked by TTX, implying that this response is not a secondary response caused by neuronal activation. Our study proposes an age-specific molecular target of DA-induced astrocytic Ca2+ signaling: MAO-B in young mice and DAR in adult mice.

show abstract

Opto-vTrap, an optogenetic trap for reversible inhibition of vesicular release, synaptic transmission, and behavior

Cited by 12 publications

References 57 publications

Dopamine-induced astrocytic Ca2+ signaling in mPFC is mediated by MAO-B in young mice, but by dopamine receptors in adult mice

Dopamine-induced astrocytic Ca2+ signaling in mPFC is mediated by MAO-B in young mice, but by dopamine receptors in adult mice

Rapid and reversible optogenetic silencing of synaptic transmission by clustering of synaptic vesicles

Dopamine-induced astrocytic Ca2+ signaling in mPFC is mediated by MAO-B in young mice, but by dopamine receptors in adult mice

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