Circuit Development and Robustness - Results

For additional data and discussion, please see the full article in Current Biology.

WTvsmutant.001.jpeg

Facial motor neurons (shown in green) normally migrate from their birthplace in rhombomere 4 (R4) to their final settling locations in rhombomeres 5-7.  However, specific mutations can disrupt that migration - leaving facial motor neurons stuck in the wrong place.

Can these mis-positioned motor neurons still incorporate into functional neural circuits?


more pics.001.jpeg

Facial motor neurons drive two groups of muscles:  several muscles on the ventral surface of the buccal cavity (left) ... 

more pics.002.jpeg

... and additional muscles over the operculum (the flap covering the opening to the gills).  These muscles are involved in suction feeding and respiration.


Whole cell recording from a facial motor neuron (orange trace) during simultaneous recording of motor activity in the tail (white trace).

In wild type larvae, facial motor neurons exhibit two patterns of respiratory activity:  infrequent bursts associated with attempted whole-body movements (shown in the box), and additional rhythmic bursts (~0.5-2Hz).  

Whole cell recording from facial motor neuron (orange trace) during simultaneous recording of motor activity in the tail (white trace). 

Surprisingly, the radically mis-positioned facial motor neurons in migration mutants also exhibit both rhythmic and body movement-associated bursting respiratory activity - suggesting that normal positioning might not be absolutely necessary for circuit development.  In other words, premotor neurons from rhythmic respiratory networks may still target facial motor neurons - even though those facial motor neurons are in the wrong place.


Orange traces represent the rotational movement of the operculum (shown in the above right inset), tracked from a video recorded at 20 frames per sec.  Note the respiratory pattern: rhythmic movements (~0.5-2Hz), followed by a large movement correlated with an attempted struggle or swim (arrows), followed by a pause before the pattern repeats.

Orange traces represent the rotational movement of the operculum (shown in the above right inset), tracked from a video recorded at 20 frames per sec.  Note the respiratory pattern: rhythmic movements (~0.5-2Hz), followed by a large movement correlated with an attempted struggle or swim (arrows), followed by a pause before the pattern repeats.

Indeed, rhythmic respiratory movements of the operculum (shown in orange) are still executed in migration mutant zebrafish - with a similar temporal pattern to that observed in wild type fish. Again, this strongly suggests that facial motor neuron function is robust to positional disruption.


Why does this matter?

We still don't completely understand the rules that determine how neurons target each other to establish synaptic connections.  We do know that some neurons search for their partners in a specific location in the brain, and that moving the partners around can severely disrupt that process and cause functional abnormalities in the animal.  Indeed, it makes sense to use neuronal positioning to guide synaptic connectivity, since many neuronal populations are reliably located in the same region of the brain across individuals.

However, in this case, facial motor neurons seem to retain at least some of their functional output when they are dramatically re-positioned, suggesting that at least some of their synaptic partners can still find them.  I'd like to understand how this robust function is achieved - and probe for more subtle defects in the mutant circuit that might be not apparent from spontaneous respiratory activity alone (and might leave the respiratory network vulnerable to specific behavioral challenges).