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Fast cerebellar reflex circuitry requires synaptic vesicle priming by Munc13-3
- Source :
- Cerebellum, Cerebellum (London, England)
- Publication Year :
- 2015
-
Abstract
- Munc13-3 is a member of the Munc13 family of synaptic vesicle priming proteins and mainly expressed in cerebellar neurons. Munc13-3 null mutant (Munc13-3 (-/-)) mice show decreased synaptic release probability at parallel fiber to Purkinje cell, granule cell to Golgi cell, and granule cell to basket cell synapses and exhibit a motor learning deficit at highest rotarod speeds. Since we detected Munc13-3 immunoreactivity in the dentate gyrus, as reported here for the first time, and current studies indicated a crucial role for the cerebellum in hippocampus-dependent spatial memory, we systematically investigated Munc13-3 (-/-) mice versus wild-type littermates of both genders with respect to hippocampus-related cognition and a range of basic behaviors, including tests for anxiety, sensory functions, motor performance and balance, sensorimotor gating, social interaction and competence, and repetitive and compulsive behaviors. Neither basic behavior nor hippocampus-dependent cognitive performance, evaluated by Morris water maze, hole board working and reference memory, IntelliCage-based place learning including multiple reversals, and fear conditioning, showed any difference between genotypes. However, consistent with a disturbed cerebellar reflex circuitry, a reliable reduction in the acoustic startle response in both male and female Munc13-3 (-/-) mice was found. To conclude, complete deletion of Munc13-3 leads to a robust decrease in the acoustic startle response. This readout of a fast cerebellar reflex circuitry obviously requires synaptic vesicle priming by Munc13-3 for full functionality, in contrast to other behavioral or cognitive features, where a nearly perfect compensation of Munc13-3 deficiency by related synaptic proteins has to be assumed.
- Subjects :
- Male
Reflex, Startle
Cerebellum
Startle response
Mice, 129 Strain
Spatial working and reference memory
Purkinje cell
Nerve Tissue Proteins
Parallel fiber
Anxiety
Hippocampus
Synaptic Transmission
IntelliCage
Mice
Cognition
Golgi cell
medicine
Animals
Maze Learning
Social Behavior
Spatial Memory
Medicine(all)
Mice, Knockout
Original Paper
Behavior, Animal
medicine.diagnostic_test
Dentate gyrus
Gender
Granule cell
Immunohistochemistry
Mice, Inbred C57BL
Memory, Short-Term
medicine.anatomical_structure
Neurology
Female
Synaptic Vesicles
Neurology (clinical)
Acoustic startle response
Psychology
Neuroscience
Psychomotor Performance
Synaptic vesicle priming
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cerebellum, Cerebellum (London, England)
- Accession number :
- edsair.doi.dedup.....f7b01a4f82d26ffe48e5be03bf6fb55f