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Preparation of Synaptic Plasma Membrane and Postsynaptic Density Proteins Using a Discontinuous Sucrose Gradient
Published on: September 3, 2014
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Fast cerebellar reflex circuitry requires synaptic vesicle priming by munc13-3
Pallavi Rao Netrakanti1, Benjamin H Cooper, Ekrem Dere
1Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Cerebellum (London, England)
|January 25, 2015
Summary
Munc13-3 protein deficiency in mice impairs cerebellar reflex circuitry, significantly reducing the acoustic startle response. However, other cognitive and basic behaviors remain unaffected, suggesting compensatory mechanisms.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Munc13-3 is a key protein in synaptic vesicle priming, primarily found in cerebellar neurons.
- Munc13-3 null mutant mice exhibit impaired synaptic release and motor learning deficits.
- Munc13-3 expression in the hippocampus was newly identified, prompting investigation into its role in cognitive functions.
Purpose of the Study:
- To investigate the behavioral and cognitive effects of Munc13-3 deficiency.
- To assess hippocampus-dependent memory and basic behaviors in Munc13-3 null mutant mice.
- To determine the role of Munc13-3 in cerebellar reflex circuitry.
Main Methods:
- Systematic behavioral and cognitive testing of Munc13-3 null mutant and wild-type mice.
- Assessment of hippocampus-dependent cognition using Morris water maze, hole board, IntelliCage, and fear conditioning.
- Evaluation of basic behaviors including anxiety, motor performance, sensorimotor gating, social interaction, and repetitive behaviors.
- Measurement of acoustic startle response to assess cerebellar reflex function.
Main Results:
- Munc13-3 null mutant mice showed no differences in basic behaviors or hippocampus-dependent cognitive performance compared to wild-type littermates.
- A significant reduction in the acoustic startle response was observed in both male and female Munc13-3 null mutant mice.
- These findings suggest Munc13-3 is crucial for the fast cerebellar reflex circuitry underlying the acoustic startle response.
Conclusions:
- Complete Munc13-3 deletion robustly impairs the acoustic startle response, highlighting its role in synaptic vesicle priming for cerebellar reflex function.
- The lack of deficits in other cognitive and behavioral domains suggests efficient compensation by related synaptic proteins in Munc13-3 deficient mice.
- Munc13-3 is essential for the full functionality of fast cerebellar reflex circuitry, but not for general cognition or basic behaviors.
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