Presenilin Regulates Retinotectal Synapse Formation through EphB2 Receptor Processing
Zhenyu Liu1, Amit Thakar1, Stephen W Santoro1
1Department of Zoology and Physiology and Program in Neuroscience, University of Wyoming, Laramie, Wyoming.
Developmental Neurobiology
|September 25, 2018
Summary
Presenilin (PS) is crucial for synapse formation in developing tadpoles, impacting visual behavior. Its role in cleaving EphB2 receptor is vital for strengthening retinotectal synapses.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Presenilin (PS) is the catalytic subunit of γ-secretase, known for cleaving amyloid precursor protein in Alzheimer's disease.
- PS/γ-secretase also processes other critical single-pass transmembrane proteins involved in development, such as Notch and EphB2 receptor.
- The function of PS in synapse formation has been difficult to study due to early embryonic lethality in knockout models.
Purpose of the Study:
- To investigate the role of presenilin (PS) in synapse formation within the developing Xenopus tadpole retinotectal circuit.
- To elucidate the specific mechanisms by which PS influences synaptic transmission and behavior in vivo.
Main Methods:
- Utilized the Xenopus tadpole retinotectal circuit as an in-vivo model for studying synapse formation.
- Manipulated protein expression specifically during the peak of synapse formation.
- Performed whole-cell recordings to assess synaptic transmission and measured visual avoidance behavior.
Main Results:
- Inhibiting PS in postsynaptic tectal neurons impaired tadpole visual avoidance behavior.
- Retinotectal synaptic transmission was weakened, with significant reductions in NMDA receptor (NMDAR)- and AMPA receptor (AMPAR)-mediated currents.
- Restoring the C-tail fragment of EphB2 receptor, a known PS/γ-secretase cleavage product, rescued reduced NMDAR-mediated responses.
Conclusions:
- Normal presenilin (PS) function is essential for the proper formation and strengthening of retinotectal synapses.
- PS facilitates synaptic development, at least in part, by cleaving the EphB2 receptor.
- This study highlights a novel role for PS in synaptic plasticity and visual circuit development.
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