The synaptic basis of activity-dependent eye-specific competition

Zhang, Chenghang; Yadav, Swapnil; Speer, Colenso M.

doi:10.1016/j.celrep.2023.112085

Cited by 4 publications

(10 citation statements)

References 107 publications

(104 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In WT mice, the total fraction of dominant-eye complex synapses increased from ~20% at P2 to ~29% at P8 while non-dominant-eye complex synapses remained constant between ~14-17% across the same period (Fig 1E, upper panel). A similar pattern of eye-specific complex synapse maturation was found in β2KO mice (Fig 1E, lower panel), showing that relative proportions of complex versus simple synapses appeared normal despite an overall reduction in total synapse density when spontaneous retinal activity was disrupted (23).…”

Section: A Unique Set Of Complex Synapses Shows Eye-specific Differen...supporting

confidence: 72%

“…We previously found that β2KO mice fail to develop eye-specific differences in vesicle recruitment to the active zone, which are normally present in WT mice as early as P2 (23). This effect is accompanied by an overall reduction in the number of retinogeniculate synapses in the β2KO mouse (23). In the current study, we found that complex synapses show greater eye-specific differences in presynaptic vesicle pool volume compared to simple synapses and that these eye-specific differences are significantly reduced in β2KO mice.…”

Section: Discussionmentioning

confidence: 99%

“…To look for evidence of synaptic clustering during eye-specific segregation, we collected super-resolution imaging data in the dLGN of wild-type (WT) mice at three postnatal time points (P2, P4, and P8) (Fig 1A). We labeled eye-specific synapses by monocular injection of Alexa Fluor-conjugated cholera toxin subunit B tracer (CTB) together with immunostaining for presynaptic Bassoon, postsynaptic Homer1, and presynaptic vesicular glutamate transporter 2 (VGluT2) proteins (23). Using volumetric STochastic Optical Reconstruction Microscopy (STORM) (24), we collected separate image volumes (~45K μm 3 each) from three biological replicates at each developmental time point.…”

Section: A Unique Set Of Complex Synapses Shows Eye-specific Differen...mentioning

confidence: 99%

“…Using volumetric STochastic Optical Reconstruction Microscopy (STORM) (24), we collected separate image volumes (~45K μm 3 each) from three biological replicates at each developmental time point. To determine whether spontaneous retinal activity impacts synaptic clustering across the same time period, we performed identical experiments in a knockout mouse line lacking the beta 2 subunit of the nicotinic acetylcholine receptor (β2KO), which disrupts spontaneous cholinergic retinal wave activity, eye-specific axonal segregation, and retinogeniculate synapse development (20,23,(25)(26)(27)(28)(29)(30)(31)(32)(33). Because eye-specific segregation is incomplete until P8 in the mouse, we limited our analysis to the future contralateral eye-specific region of the dLGN, which is reliably identified across all To further investigate complex synapse maturation, we measured the fraction of complex synapses relative to the total synapse number over development.…”

Section: A Unique Set Of Complex Synapses Shows Eye-specific Differen...mentioning

confidence: 99%

See 3 more Smart Citations

Eye-specific synaptic clustering through activity-dependent stabilization and punishment mechanisms in the developing visual system

Zhang,

Speer

2023

Preprint

Self Cite

View full text Add to dashboard Cite

Co-active synaptic connections are often spatially clustered to enable local dendritic computations underlying learning, memory, and basic sensory processing. In the mammalian visual system, retinal ganglion cell (RGC) axons converge to form clustered synaptic inputs for local signal integration in the dorsal lateral geniculate nucleus (dLGN) of the thalamus. Retinogeniculate synapse clustering is promoted by visual experience after eye-opening, but the earliest events in cluster formation and potential regulation by spontaneous retinal wave activity prior to visual experience are unknown. Here, using volumetric super-resolution single-molecule localization microscopy together with eye-specific labeling of developing retinogeniculate synapses in the mouse, we show that synaptic clustering is eye-specific and activity-dependent during the first postnatal week. We identified a subset of complex retinogeniculate synapses with larger presynaptic vesicle pools and multiple active zones that simultaneously promote the clustering of like-eye synapses (synaptic stabilization) and prohibit synapse clustering from the opposite eye (synaptic punishment). In mutant mice with disrupted spontaneous retinal wave activity, complex synapses form, but fail to drive eye-specific synaptic clustering and punishment seen in controls. These results highlight a role for spontaneous retinal activity in regulating eye-specific stabilization and punishment signals contributing to synaptic clustering in circuits essential for visual perception and behavior.

show abstract

Section: A Unique Set Of Complex Synapses Shows Eye-specific Differen...supporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: A Unique Set Of Complex Synapses Shows Eye-specific Differen...mentioning

confidence: 99%

Section: A Unique Set Of Complex Synapses Shows Eye-specific Differen...mentioning

confidence: 99%

See 2 more Smart Citations

Eye-specific synaptic clustering through activity-dependent stabilization and punishment mechanisms in the developing visual system

Zhang,

Speer

2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Together, these results suggest that SCN circuit maturation after eye-opening occurs by synapse addition without a significant change in presynaptic size or protein abundance within individual synaptic terminals. This pattern of RHT development stands in contrast to the development of image-forming retinal projections to the dorsal lateral geniculate nucleus (dLGN), which show a progressive increase in synapse size over development before and after eye-opening. − …”

Section: Discussionmentioning

confidence: 91%

Microanalytical Mass Spectrometry with Super-Resolution Microscopy Reveals a Proteome Transition During Development of the Brain’s Circadian Pacemaker

Choi,

Vatan,

Alexander

et al. 2023

Anal. Chem.

Self Cite

View full text Add to dashboard Cite

During brain development, neuronal proteomes are regulated in part by changes in spontaneous and sensory-driven activity in immature neural circuits. A longstanding model for studying activity-dependent circuit refinement is the developing mouse visual system where the formation of axonal projections from the eyes to the brain is influenced by spontaneous retinal activity prior to the onset of vision and by visual experience after eye-opening. The precise proteomic changes in retinorecipient targets that occur during this developmental transition are unknown. Here, we developed a microanalytical proteomics pipeline using capillary electrophoresis (CE) electrospray ionization (ESI) mass spectrometry (MS) in the discovery setting to quantify developmental changes in the chief circadian pacemaker, the suprachiasmatic nucleus (SCN), before and after the onset of photoreceptor-dependent visual function. Nesting CE-ESI with trapped ion mobility spectrometry time-of-flight (TOF) mass spectrometry (TimsTOF PRO) doubled the number of identified and quantified proteins compared to the TOF-only control on the same analytical platform. From 10 ng of peptide input, corresponding to <∼0.5% of the total local tissue proteome, technical triplicate analyses identified 1894 proteins and quantified 1066 proteins, including many with important canonical functions in axon guidance, synapse function, glial cell maturation, and extracellular matrix refinement. Label-free quantification revealed differential regulation for 166 proteins over development, with enrichment of axon guidance-associated proteins prior to eye-opening and synapse-associated protein enrichment after eye-opening. Super-resolution imaging of select proteins using STochastic Optical Reconstruction Microscopy (STORM) corroborated the MS results and showed that increased presynaptic protein abundance pre/post eye-opening in the SCN reflects a developmental increase in synapse number, but not presynaptic size or extrasynaptic protein expression. This work marks the first development and systematic application of TimsTOF PRO for CE-ESI-based microproteomics and the first integration of microanalytical CE-ESI TimsTOF PRO with volumetric super-resolution STORM imaging to expand the repertoire of technologies supporting analytical neuroscience.

show abstract

Eye-specific synaptic clustering through activity-dependent stabilization and punishment mechanisms in the developing visual system

Zhang,

Speer

2023

Preprint

View full text Add to dashboard Cite

show abstract

The synaptic basis of activity-dependent eye-specific competition

Cited by 4 publications

References 107 publications

Eye-specific synaptic clustering through activity-dependent stabilization and punishment mechanisms in the developing visual system

Eye-specific synaptic clustering through activity-dependent stabilization and punishment mechanisms in the developing visual system

Microanalytical Mass Spectrometry with Super-Resolution Microscopy Reveals a Proteome Transition During Development of the Brain’s Circadian Pacemaker

Eye-specific synaptic clustering through activity-dependent stabilization and punishment mechanisms in the developing visual system

Contact Info

Product

Resources

About