A genetically encoded tool for reconstituting synthetic modulatory neurotransmission and reconnect neural circuits in vivo

Hawk, Joshua D.; Wisdom, Elias; Sengupta, Titas; Kashlan, Zane D.; Colón-Ramos, Daniel A.

doi:10.1038/s41467-021-24690-9

Cited by 15 publications

(7 citation statements)

References 46 publications

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“…Using chemical and genetic approaches, we increase and decrease Kenyon cell number and Kenyon cell input number. This approach adds to a growing body of literature in which researchers engineer cell biological changes to neurons in order to probe developmental algorithms or change circuit function (Dzirasa et al, 2022;Hawk et al, 2021;Heckman and Doe, 2022;Linneweber et al, 2020;Meng et al, 2019;Pechuk et al, 2022;Pop et al, 2020;Prieto-Godino et al, 2020). Both the developmental and functional results force us to rethink assumptions and predictions about how the structure of connectivity influences odor representations and learned associations.…”

Section: Discussionmentioning

confidence: 99%

Hacking brain development to test models of sensory coding

Ahmed

Rajagopalan

Pan

et al. 2023

Preprint

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Animals can discriminate myriad sensory stimuli but can also generalize from learned experience. You can probably distinguish the favorite teas of your colleagues while still recognizing that all tea pales in comparison to coffee. Tradeoffs between detection, discrimination, and generalization are inherent at every layer of sensory processing. During development, specific quantitative parameters are wired into perceptual circuits and set the playing field on which plasticity mechanisms play out. A primary goal of systems neuroscience is to understand how material properties of a circuit define the logical operations--computations--that it makes, and what good these computations are for survival. A cardinal method in biology--and the mechanism of evolution--is to change a unit or variable within a system and ask how this affects organismal function. Here, we make use of our knowledge of developmental wiring mechanisms to modify hard-wired circuit parameters in the Drosophila melanogaster mushroom body and assess the functional and behavioral consequences. By altering the number of expansion layer neurons (Kenyon cells) and their dendritic complexity, we find that input number, but not cell number, tunes odor selectivity. Simple odor discrimination performance is maintained when Kenyon cell number is reduced and augmented by Kenyon cell expansion.

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Section: Discussionmentioning

confidence: 99%

Hacking brain development to test models of sensory coding

Ahmed

Rajagopalan

Pan

et al. 2023

Preprint

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“…Activity-dependent release of biologically active allatostatin from presynaptic neurons induces inhibition of allatostatin receptor-expressing subpopulations of postsynaptic neurons. The other system uses a Hydra derived presynaptically expressed neuropeptide and a matching postsynaptic cation channel that is opened by the peptide 41 . Upon activity-dependent presynaptic peptide release this heterologous synapse creates novel calcium fluxes postsynaptically and resulting in neural activation.…”

Section: Discussionmentioning

confidence: 99%

Selective control of synaptically-connected circuit elements by all-optical synapses

et al. 2022

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Understanding percepts, engrams and actions requires methods for selectively modulating synaptic communication between specific subsets of interconnected cells. Here, we develop an approach to control synaptically connected elements using bioluminescent light: Luciferase-generated light, originating from a presynaptic axon terminal, modulates an opsin in its postsynaptic target. Vesicular-localized luciferase is released into the synaptic cleft in response to presynaptic activity, creating a real-time Optical Synapse. Light production is under experimenter-control by introduction of the small molecule luciferin. Signal transmission across this optical synapse is temporally defined by the presence of both the luciferin and presynaptic activity. We validate synaptic Interluminescence by multi-electrode recording in cultured neurons and in mice in vivo. Interluminescence represents a powerful approach to achieve synapse-specific and activity-dependent circuit control in vivo.

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“…A variety of ChRs that are activated by different wavelengths have been discovered or engineered (Guru et al, 2015;Schild and Glauser, 2015;Chang, 2019). This enables multiplexing with both short-or long-wavelength absorbing fluorophores (Wabnig et al, 2015;Hawk et al, 2021;Vierock et al, 2021). In this work, we characterize two different combinations of ChRs with pH-sensitive fluorescent proteins in living C. elegans nematodes.…”

Section: Introductionmentioning

confidence: 99%

pOpsicle: An all-optical reporter system for synaptic vesicle recycling combining pH-sensitive fluorescent proteins with optogenetic manipulation of neuronal activity

Seidenthal

Jánosi

Rosenkranz

et al. 2023

Front. Cell. Neurosci.

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pH-sensitive fluorescent proteins are widely used to study synaptic vesicle (SV) fusion and recycling. When targeted to the lumen of SVs, fluorescence of these proteins is quenched by the acidic pH. Following SV fusion, they are exposed to extracellular neutral pH, resulting in a fluorescence increase. SV fusion, recycling and acidification can thus be tracked by tagging integral SV proteins with pH-sensitive proteins. Neurotransmission is generally activated by electrical stimulation, which is not feasible in small, intact animals. Previous in vivo approaches depended on distinct (sensory) stimuli, thus limiting the addressable neuron types. To overcome these limitations, we established an all-optical approach to stimulate and visualize SV fusion and recycling. We combined distinct pH-sensitive fluorescent proteins (inserted into the SV protein synaptogyrin) and light-gated channelrhodopsins (ChRs) for optical stimulation, overcoming optical crosstalk and thus enabling an all-optical approach. We generated two different variants of the pH-sensitive optogenetic reporter of vesicle recycling (pOpsicle) and tested them in cholinergic neurons of intact Caenorhabditis elegans nematodes. First, we combined the red fluorescent protein pHuji with the blue-light gated ChR2(H134R), and second, the green fluorescent pHluorin combined with the novel red-shifted ChR ChrimsonSA. In both cases, fluorescence increases were observed after optical stimulation. Increase and subsequent decline of fluorescence was affected by mutations of proteins involved in SV fusion and endocytosis. These results establish pOpsicle as a non-invasive, all-optical approach to investigate different steps of the SV cycle.

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A genetically encoded tool for reconstituting synthetic modulatory neurotransmission and reconnect neural circuits in vivo

Cited by 15 publications

References 46 publications

Hacking brain development to test models of sensory coding

Hacking brain development to test models of sensory coding

Selective control of synaptically-connected circuit elements by all-optical synapses

pOpsicle: An all-optical reporter system for synaptic vesicle recycling combining pH-sensitive fluorescent proteins with optogenetic manipulation of neuronal activity

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