Motor control: Snake neurons speed up.

How are motor neurons tuned for very different jobs? Classic work has focused on variations in motor neuron size and their premotor networks. New results in rattlesnakes show that shifting a motor neuron's temporal precision can be as simple as changing its potassium channel conductance.

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

Shared lineage has diverse effects on patterns of neuronal connectivity. In mammalian cortex, excitatory sister neurons assemble into shared microcircuits. In Drosophila, in contrast, sister neurons with different levels of Notch expression (NotchON/NotchOFF) develop distinct identities and diverge into separate circuits. Notch-differentiated sister neurons have been observed in vertebrate spinal cord and cerebellum, but whether they integrate into shared or distinct circuits remains unknown. Here, we evaluate how sister V2a (NotchOFF)/V2b (NotchON) neurons in the zebrafish integrate into spinal circuits. Using an in vivo labeling approach, we identified pairs of sister V2a/b neurons born from individual Vsx1+ progenitors and observed that they have somata in close proximity to each other and similar axonal trajectories. However, paired whole-cell electrophysiology and optogenetics revealed that sister V2a/b neurons receive input from distinct presynaptic sources, do not communicate with each other, and connect to largely distinct targets. These results resemble the divergent connectivity in Drosophila and represent the first evidence of Notch-differentiated circuit integration in a vertebrate system.

The brain is populated by neurons which are generated during embryonic development from cells called progenitors. Neurons that come from the same progenitor cell are considered to be 'sisters'. In certain brain regions of mice, sister neurons are often wired into shared networks, meaning they are more likely to receive input from the same neurons and connect with each other than non-sister cells. In contrast, in invertebrate animals, like the fruit fly, sister neurons often have different identities and are less likely to connect with each other. This may be because sister neurons in fruit flies often have varied levels of a protein called Notch, which plays an important role in establishing the identity of cells. Vertebrate and invertebrate animals are different in many respects, and it remained unclear whether Notch levels dictate which sister neurons connect together in vertebrates as they do in fruit flies. To investigate, Bello-Rojas and Bagnall studied two neurons in the spinal cord of zebrafish embryos which come from the same type of progenitor cell: the V2a neuron which has low levels of Notch, and the V2b neuron which has high levels of Notch. Fish, like humans, are vertebrates; however, their embryos are mostly transparent, making it easier to track how their neurons make connections during development using a microscope. This enabled Bello-Rojas and Bagnall to monitor whether V2a and V2b sister neurons joined the same network, like in other vertebrates, or different networks, akin to sister neurons in fruit flies which also have differing levels of Notch. Bello-Rojas and Bagnall found that sister V2a and V2b neurons stayed close to one another and seemed to connect through similar paths. However, closer investigation revealed that the sister neurons did not receive input from the same source. They also did not connect to each other or the same output neuron, suggesting that V2a and V2b sister neurons are part of different networks. This is the first time Notch levels have been shown to regulate which network a neuron will join in a vertebrate species. Since the V2a and V2b neurons are involved in controlling body movement, future work should determine whether adding progenitor cells that produce these neurons into the spinal cord could help the neuron network recover after injury or disease.

Central and peripheral innervation patterns of defined axial motor units in larval zebrafish.

Spinal motor neurons and the peripheral muscle fibers they innervate form discrete motor units that execute movements of varying force and speed. Subsets of spinal motor neurons also exhibit axon collaterals that influence motor output centrally. Here, we have used in vivo imaging to anatomically characterize the central and peripheral innervation patterns of axial motor units in larval zebrafish. Using early born "primary" motor neurons and their division of epaxial and hypaxial muscle into four distinct quadrants as a reference, we define three distinct types of later born "secondary" motor units. The largest is "m-type" units, which innervate deeper fast-twitch muscle fibers via medial nerves. Next in size are "ms-type" secondaries, which innervate superficial fast-twitch and slow fibers via medial and septal nerves, followed by "s-type" units, which exclusively innervate superficial slow muscle fibers via septal nerves. All types of secondaries innervate up to four axial quadrants. Central axon collaterals are found in subsets of primaries based on soma position and predominantly in secondary fast-twitch units (m, ms) with increasing likelihood based on number of quadrants innervated. Collaterals are labeled by synaptophysin-tagged fluorescent proteins, but not PSD95, consistent with their output function. Also, PSD95 dendrite labeling reveals that larger motor units receive more excitatory synaptic input. Collaterals are largely restricted to the neuropil, however, perisomatic connections are observed between motor units. These observations suggest that recurrent interactions are dominated by motor neurons recruited during stronger movements and set the stage for functional investigations of recurrent motor circuitry in larval zebrafish.