Research Highlight: Optimization of a genetically-encoded toxin reveals new roles for interneurons involved in locomotion

All animals depend on locomotion for survival, and the precise control of locomotion is critical for adapting behavior to different environmental contexts. Which neurons contribute to initiating and driving different speeds of locomotion? Jenna Sternberg (ENP student) and Kristen Severi led a study to address this question in the team of Claire Wyart (ENP team leader) at the Brain and Spine Institute (ICM) in collaboration with Norwegian and Japanese teams. V2a interneurons are located in the hindbrain and spinal cord and play critical roles during locomotion in both zebrafish and mammals. Using a novel genetically-encoded botulinum toxin to specifically silence neurons in the zebrafish, the team found that the V2a neurons are necessary for initiating slow locomotion and for controlling speed in function of the situation.

Check out the article:

Optimization of a Neurotoxin to Investigate the Contribution of Excitatory Interneurons to Speed Modulation In Vivo. Jenna R. Sternberg, Kristen E. Severi, Kevin Fidelin, Johanna Gomez, Hideshi Ihara, Yara Alcheikh, Jeffrey M. Hubbard, Koichi Kawakami, Maximiliano Suster, Claire Wyart. Current Biol. (2016). Epub 11 August 2016



A.     Schematic of the mechanism of botulinum neurotoxin. Genetically encoded botulinum neurotoxin (BoTxBLC-GFP) blocks communication between neurons by preventing neurotransmitter release from pre-synaptic neurons. 

B.    Lateral view of a zebrafish larvae at five days post fertilization expressing genetically encoded botulinum neurotoxin in excitatory V2a pre-motor interneurons. 

C.     Dorsal view of a head-embedded, tail-free zebrafish larvae executing a startle response to an acoustic stimulus. In wild type larvae, larvae respond to the stimulus with a fast swim. When V2a interneurons are silenced, larvae fail to produce high speed swimming. 

D.  Swimming frequency reflecting swimming speed in wild type larvae and V2a-silenced larvae.