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The Cerebellum
Published in: The Cerebellum 3/2015

Open Access 01-06-2015 | Original Paper

Fast Cerebellar Reflex Circuitry Requires Synaptic Vesicle Priming by Munc13-3

Authors: Pallavi Rao Netrakanti, Benjamin H. Cooper, Ekrem Dere, Giulia Poggi, Daniela Winkler, Nils Brose, Hannelore Ehrenreich

Published in: The Cerebellum | Issue 3/2015

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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.
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Metadata
Title
Fast Cerebellar Reflex Circuitry Requires Synaptic Vesicle Priming by Munc13-3
Authors
Pallavi Rao Netrakanti
Benjamin H. Cooper
Ekrem Dere
Giulia Poggi
Daniela Winkler
Nils Brose
Hannelore Ehrenreich
Publication date
01-06-2015
Publisher
Springer US
Published in
The Cerebellum / Issue 3/2015
Print ISSN: 1473-4222
Electronic ISSN: 1473-4230
DOI
https://doi.org/10.1007/s12311-015-0645-0

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