Decoding Neurotransmitter Switching: The Road Forward

Li, Huiquan; Pratelli, Marta; Godavarthi, Swetha K.; Zambetti, Stefania; Spitzer, Nicholas C.

doi:10.1523/jneurosci.0005-20.2020

Cited by 18 publications

(13 citation statements)

References 125 publications

(173 reference statements)

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“…See illustrative examples from the sea urchin (Wei et al, 2011 ), cnidarians (Nakanishi et al, 2012 ), including recent scRNA-seq work (Arendt, 2019 ; Siebert et al, 2019 ), and ctenophores (Moroz et al, 2014 ; Moroz, 2015a ). Trans-differentiation with transmitter phenotype switching both in development and adult brains is possible (Spitzer, 2017 ; Bertuzzi et al, 2018 ; Meng et al, 2018 ; Ferrarelli, 2020 ; Li et al, 2020 ). But it might be a relatively rare event stressing both modularity and substantial evolutionary conservation of secretory specificity within the lineages of homologous neurons.…”

Section: Postulates Of the Polygeny Hypothesismentioning

confidence: 99%

Multiple Origins of Neurons From Secretory Cells

Moroz

2021

Front. Cell Dev. Biol.

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Section: Postulates Of the Polygeny Hypothesismentioning

confidence: 99%

Multiple Origins of Neurons From Secretory Cells

Moroz

2021

Front. Cell Dev. Biol.

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“…In this way, instead of a few thousands of newborn DGCs ready to switch (3–6% of the whole population [ van Praag et al, 1999 ; Cameron and McKay, 2001 ], divided by 30 days), a larger fraction of newborn DGCs would be made available for coding, if appropriate stimulation occurs. Finally, while neurotransmitter switching has been observed following sustained stimulation for hours to days ( Li et al, 2020 ), it is still unclear if it has the same functional role as the GABA-switch in our model. In particular, it remains an open question if neurotransmitter switching promotes the integration of neurons in the same way as our model GABA-switch does in the context of adult dentate gyrus neurogenesis.…”

Section: Discussionmentioning

confidence: 88%

A functional model of adult dentate gyrus neurogenesis

Gozel

Gerstner

2021

eLife

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In adult dentate gyrus neurogenesis, the link between maturation of newborn neurons and their function, such as behavioral pattern separation, has remained puzzling. By analyzing a theoretical model, we show that the switch from excitation to inhibition of the GABAergic input onto maturing newborn cells is crucial for their proper functional integration. When the GABAergic input is excitatory, cooperativity drives the growth of synapses such that newborn cells become sensitive to stimuli similar to those that activate mature cells. When GABAergic input switches to inhibitory, competition pushes the configuration of synapses onto newborn cells towards stimuli that are different from previously stored ones. This enables the maturing newborn cells to code for concepts that are novel, yet similar to familiar ones. Our theory of newborn cell maturation explains both how adult-born dentate granule cells integrate into the preexisting network and why they promote separation of similar but not distinct patterns.

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“…This lack of specificity likely reflects cellular fate specification in the developing tadpole brain. Neurons at the stages of development used in our study can dynamically switch neurotransmitter expression ( Borodinsky et al, 2004 ; Dulcis et al, 2013 ; Li et al, 2020 ). Furthermore, the inhibitory neuron markers GABA and GAD67, and the excitatory neuron marker CaMKII, are regulated by visual activity in the tadpole optic tectum ( Miraucourt et al, 2012 ; Shen et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Application of Recombinant Rabies Virus toXenopusTadpole Brain

Faulkner

Wall

Callaway

et al. 2021

eNeuro

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The Xenopus laevis experimental system has provided significant insight into the development and plasticity of neural circuits. Xenopus neuroscience research would be enhanced by additional tools to study neural circuit structure and function. Rabies viruses are powerful tools to label and manipulate neural circuits and have been widely used to study mesoscale connectomics. Whether rabies virus can be used to transduce neurons and express transgenes in Xenopus has not been systematically investigated. Glycoprotein-deleted rabies virus transduces neurons at the axon terminal and retrogradely labels their cell bodies. We show that glycoproteindeleted rabies virus infects local and projection neurons in the Xenopus tadpole when directly injected into brain tissue. Pseudotyping glycoprotein-deleted rabies with EnvA restricts infection to cells with exogenous expression of the EnvA receptor, TVA. EnvA pseudotyped virus specifically infects tadpole neurons with promoter-driven expression of TVA, demonstrating its utility to label targeted neuronal populations. Neuronal cell types are defined by a combination of features including anatomical location, expression of genetic markers, axon projection sites, morphology, and physiological properties. We show that driving TVA expression in one hemisphere and injecting EnvA pseudotyped virus into the contralateral hemisphere, retrogradely labels neurons defined by cell body location and axon projection site. Using this approach, rabies can be used to identify cell types in Xenopus brain and simultaneously to express transgenes which enable monitoring or manipulation of neuronal activity. This makes rabies a valuable tool to study the structure and function of neural circuits in Xenopus. Significance StatementStudies in Xenopus have contributed a great deal to our understanding of brain circuit development and plasticity, regeneration, and hormonal regulation of behavior and metamorphosis. Here, we show that recombinant rabies virus transduces neurons in the Xenopus tadpole, enlarging the toolbox that can be applied to studying Xenopus brain. Rabies can be used for retrograde labeling and expression of a broad range of transgenes including fluorescent proteins for anatomical tracing and studying neuronal morphology, voltage or calcium indicators to visualize neuronal activity, and photo-or chemosensitive channels to control neuronal activity. The versatility of these tools enables diverse experiments to analyze and manipulate Xenopus brain structure and function, including mesoscale connectivity.

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Decoding Neurotransmitter Switching: The Road Forward

Cited by 18 publications

References 125 publications

Multiple Origins of Neurons From Secretory Cells

Multiple Origins of Neurons From Secretory Cells

A functional model of adult dentate gyrus neurogenesis

Application of Recombinant Rabies Virus toXenopusTadpole Brain

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