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A Model to Study NMDA Receptors in Early Nervous System Development
Josiah D Zoodsma1,2, Kelvin Chan1,3,2, Ashwin A Bhandiwad4
1Graduate Program in Neuroscience.
Summary
Zebrafish lacking N-methyl-D-aspartate receptors (NMDARs) survive early development, offering a new model to study NMDAR function. This research reveals acute and developmental effects of NMDAR absence on zebrafish behavior.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- N-methyl-D-aspartate receptors (NMDARs) are crucial for neuronal development and function.
- Studying the long-term absence of NMDARs in vertebrates has been limited by experimental challenges.
Purpose of the Study:
- To develop a zebrafish model for studying NMDARs in early vertebrate development.
- To investigate the roles of NMDARs in the developing nervous system and behavior.
Main Methods:
- CRISPR-mediated gene editing to create lesions in zebrafish NMDAR genes (grin1a and grin1b).
- Generation of double-mutant zebrafish (grin1a-/-; grin1b-/-) lacking all NMDAR-mediated synaptic transmission.
- Behavioral analysis of mutant zebrafish larvae, including responses to stimuli and habituation.
Main Results:
- Zebrafish lacking both grin1a and grin1b genes are viable until approximately 10 days post-fertilization.
- Mutant zebrafish exhibit behavioral defects, including abnormal responses to light and sound, and impaired prey capture.
- Some behavioral defects are mimicked by NMDAR antagonist MK-801, suggesting acute effects, while others indicate developmental origins.
Conclusions:
- A novel zebrafish model allows for the study of NMDAR function during early vertebrate development.
- This model provides insights into both acute and developmental consequences of NMDAR absence on nervous system function and behavior.
