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Updated: Jan 29, 2026
09:09
Electrophysiological Investigations of Retinogeniculate and Corticogeniculate Synapse Function
Published on: August 7, 2019
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Presynaptic SNAP-25 regulates retinal waves and retinogeniculate projection via phosphorylation
Yu-Tien Hsiao1, Wen-Chi Shu1, Pin-Chun Chen1
1Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 10617, Taiwan.
Summary
Synaptosome-associated protein of 25 kDa (SNAP-25) regulates retinal waves in developing retinas. Phosphorylation of SNAP-25 by PKA in starburst amacrine cells (SACs) dampens wave activity, influencing visual circuit refinement.
Area of Science:
- Neuroscience
- Developmental Biology
- Retinal Circuitry
Background:
- Developing retinas exhibit patterned spontaneous activity called retinal waves, crucial for visual circuit refinement.
- Starburst amacrine cells (SACs) initiate these waves in neonatal rodents, which propagate to retinal ganglion cells (RGCs) and beyond.
- While retinal waves correlate with protein kinase A (PKA) activity, the specific PKA target regulating SAC transmission remains unknown.
Purpose of the Study:
- To investigate the role of synaptosome-associated protein of 25 kDa (SNAP-25) in SACs in regulating retinal wave properties and retinogeniculate projections during development.
- To determine if PKA-mediated phosphorylation of SNAP-25 is critical for its function in retinal wave regulation.
Main Methods:
- Overexpression of wild-type and PKA-phosphorylation-deficient SNAP-25b mutants in SACs.
- Measurement of wave-associated calcium transients in RGCs.
- Electrophysiological recordings of spontaneous, wave-associated, postsynaptic currents in RGCs.
- Knockdown of endogenous SNAP-25b in SACs.
- Assessment of eye-specific retinogeniculate projection following in vivo manipulation of SNAP-25b in SACs.
Main Results:
- Overexpression of wild-type SNAP-25b, but not the T138A mutant, in SACs reduced wave frequency and spatial correlation.
- SNAP-25b overexpression in SACs decreased RGC postsynaptic currents and SAC release, suggesting PKA-mediated inhibition via T138 phosphorylation.
- Knockdown of endogenous SNAP-25b increased wave frequency, confirming SNAP-25's role in restraining wave periodicity.
- Impaired eye-specific retinogeniculate segregation was observed with in vivo SNAP-25b overexpression in SACs.
Conclusions:
- SNAP-25 in developing SACs acts as a PKA substrate, dampening retinal wave spatiotemporal properties through phosphorylation at T138.
- This regulation by SNAP-25 limits excessive wave activity, thereby playing a critical role in proper visual circuit refinement and retinogeniculate projection patterning.
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