Clonally related, Notch-differentiated spinal neurons integrate into distinct circuits

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Neuronal connectivity is influenced by shared lineage, with varied outcomes across species.
• In mammals, sister neurons form shared microcircuits, while in Drosophila, Notch signaling drives distinct neuronal fates and separate circuits.
• Notch-differentiated sister neurons exist in vertebrate spinal cord and cerebellum, but their circuit integration is poorly understood.

Purpose of the Study:

• To investigate how sister V2a (Notch-OFF) and V2b (Notch-ON) neurons in zebrafish integrate into spinal circuits.
• To determine if Notch-differentiated sister neurons in vertebrates form shared or distinct circuits.

Main Methods:

• In vivo labeling to identify sister V2a/b neuron pairs from Vsx1+ progenitors.
• Paired whole-cell electrophysiology and optogenetics to analyze neuronal connectivity and function.

Main Results:

• Sister V2a/b neurons originate from the same progenitor, exhibiting close somata proximity and similar axonal paths.
• Electrophysiological analysis revealed distinct presynaptic inputs for sister V2a/b neurons.
• These sister neurons do not communicate directly and connect to largely separate downstream targets.

Conclusions:

• Sister V2a/b neurons in zebrafish exhibit divergent circuit integration, similar to Drosophila.
• This study provides the first evidence of Notch-differentiated sister neuron circuit integration in a vertebrate system.
• Shared lineage with differential Notch signaling leads to distinct neuronal fates and circuit segregation in vertebrates.