Synapse-specific burst coding sustained by local axonal translation

Wong, Hovy Ho-Wai; Watt, Alanna J.; Sjöström, P. Jesper

doi:10.1016/j.neuron.2023.10.011

Cited by 3 publications

(5 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dendritic translation is also robustly implicated in long-term synaptic plasticity in mature neurons (Huber et al, 2000; Kang & Schuman, 1996) and presynaptic axonal translation occurs during synapse formation (Wong et al, 2017). Additionally, while RNA granules have been shown to dynamically move along main axons and dendrites, there is some evidence that stationary RNA granules not only localize to pre-synaptic terminals (Wong et al, 2023), but also translocate towards synaptic spine heads upon neuronal stimulation (Mitsumori et al, 2017). This indicates facilitation of local translation-dependent synapse formation is based on the function of stationary ribosomes near synapses.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, while RNA granules have been shown to dynamically move along main axons and dendrites, there is some evidence that stationary RNA granules not only localize to pre-synaptic terminals (Wong et al, 2023), but also translocate towards synaptic spine heads upon neuronal stimulation (Mitsumori et al, 2017). This indicates facilitation of local translation-dependent synapse formation is based on the function of stationary ribosomes near synapses.…”

Section: A -F)mentioning

confidence: 99%

See 1 more Smart Citation

Schizophrenia risk gene ZNF804A controls ribosome localization and synaptogenesis in developing human neurons

Sichlinger,

Wulf,

Dutan Polit

et al. 2024

Preprint

View full text Add to dashboard Cite

ZNF804A was amongst the first genes robustly associated with schizophrenia based on findings from large-scale genomic studies. Previous research has implicated ZNF804A in the regulation of gene expression and synaptic function, but the role of this gene in neurodevelopment and in schizophrenia pathogenesis remains unclear. To study its function during neurodevelopment, we generated isogenic human induced pluripotent stem cells (hiPSCs) with reduced ZNF804A expression, differentiated them into developing cortical glutamatergic neurons and studied their transcriptomic, synaptic and protein signatures. Mutant neurons showed modest evidence changes in gene expression. However, high-content confocal imaging revealed increased excitatory synapse density in mutant neurons. Cell-compartment specific proteomic analysis further revealed that mutant neurons had higher levels of ribosomal and translational proteins within neurites, and high-content imaging confirmed increased local protein synthesis efficiency. Overall, these results demonstrate that in human developing cortical glutamatergic neurons, ZNF804A regulates excitatory synapse formation potential via increased local protein translation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: A -F)mentioning

confidence: 99%

Schizophrenia risk gene ZNF804A controls ribosome localization and synaptogenesis in developing human neurons

Sichlinger,

Wulf,

Dutan Polit

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Ideally, however, opsins in postsynaptic cells should be specifically blocked by drug dialysis via the recording pipette. 46,51 Development of such pharmacology would be a key step forward for optomapping reliability.…”

Section: Discussionmentioning

confidence: 99%

“…[13][14][15] We therefore independently categorized postsynaptic cells into PC, BC, and MC classes using hierarchical clustering based on morphological and electrophysiological characteristics (Figure S4). 51 These characteristics were obtained by patch clamp followed by biocytin histology and confocal imaging (Figure 1I and S5; see Methods). Excitatory and inhibitory neuron properties were consistent with prior descriptions [18][19][20] indicating that we accurately classified PCs, BCs, and MCs.…”

Section: Identification Of Pcs Bcs and Mcsmentioning

confidence: 99%

“…So, although PC→PC optomapping chiefly reproduced the known canonical circuit with some fine-tuning, the layer-specificity of PC→BC and PC→MC drive was surprising. For example, MCs have been thoroughly studied in L5, 21,23,24,46,51,76 yet are much more strongly driven in L2/3, hinting at a key functional relevance in the computational layer. Similarly, the potent PC→BC drive in L5 suggests a prominent BC role in the output layer.…”

Section: The Ubiquitous Log-normal Distributionmentioning

confidence: 99%

See 1 more Smart Citation

Principles of visual cortex excitatory microcircuit organization

Chou,

Wong,

Guo

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Microcircuit function is determined by patterns of connectivity and short-term plasticity that vary with synapse type. Elucidating microcircuit function therefore requires synapse-specific investigation. The state of the art for synapse-specific measurements has long been paired recordings. Although powerful, this method is slow, leading to a throughput problem. To improve yield, we therefore created optomapping — an approximately 100-fold faster 2-photon optogenetic method — which we validated with paired-recording data. Using optomapping, we tested 15,433 candidate excitatory inputs to find 1,184 connections onto pyramidal, basket, and Martinotti cells in mouse primary visual cortex, V1. We measured connectivity, synaptic weight, and short-term dynamics across the V1 layers. We found log-normal synaptic strength distributions, even in individual inhibitory cells, which was previously not known. We reproduced the canonical circuit for pyramidal cells but found surprising and differential microcircuit structures, with excitation of basket cells concentrated to layer 5, and excitation of Martinotti cells dominating in layer 2/3. Excitation of inhibitory cells was denser, stronger, and farther-reaching than excitation of excitatory cells, which promotes stability and difference-of-Gaussian connectivity. We gathered an excitatory short-term plasticitome, which revealed that short-term plasticity is simultaneously target-cell specific and dependent on presynaptic cortical layer. Peak depolarization latency in pyramidal cells also emerged as more heterogeneous, suggesting heightened sensitivity to redistribution of synaptic efficacy. Optomapping additionally revealed high-order connectivity patterns including shared-input surplus for interconnected pyramidal cells in layer 6. Optomapping thus offered both resolution to the throughput problem and novel insights into the principles of neocortical excitatory fine structure.

show abstract

Microglia shapes; SCN3A gene; leptin’s role in antipsychotic-induced weight gain

Adams

2023

The Transmitter

View full text Add to dashboard Cite

Synapse-specific burst coding sustained by local axonal translation

Cited by 3 publications

References 76 publications

Schizophrenia risk gene ZNF804A controls ribosome localization and synaptogenesis in developing human neurons

Schizophrenia risk gene ZNF804A controls ribosome localization and synaptogenesis in developing human neurons

Principles of visual cortex excitatory microcircuit organization

Microglia shapes; SCN3A gene; leptin’s role in antipsychotic-induced weight gain

Contact Info

Product

Resources

About