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Origins of Spinal V2a Rhythmicity at...

Agha, Moneeza Akbar,

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Origins of Spinal V2a Rhythmicity at Different Locomotor Speeds in Larval Zebrafish /

Record Type:	Electronic resources : Monograph/item
Title/Author:	Origins of Spinal V2a Rhythmicity at Different Locomotor Speeds in Larval Zebrafish // Moneeza Akbar Agha.
Author:	Agha, Moneeza Akbar,
Description:	1 electronic resource (96 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 85-11, Section: B.
Contained By:	Dissertations Abstracts International85-11B.
Subject:	Neurosciences. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31292590
ISBN:	9798382762913

Origins of Spinal V2a Rhythmicity at Different Locomotor Speeds in Larval Zebrafish /
Agha, Moneeza Akbar,

Origins of Spinal V2a Rhythmicity at Different Locomotor Speeds in Larval Zebrafish /Moneeza Akbar Agha. - 1 electronic resource (96 pages)

Source: Dissertations Abstracts International, Volume: 85-11, Section: B.

While locomotor rhythms are known to be generated by spinal circuits, the mechanisms underpinning this inherent capacity for rhythmogenesis remain intensely debated. It has been proposed that such locomotor rhythms are driven by intrinsic pacemakers, emergent network properties, or some combination of the two. Additionally, even though locomotion at different speeds is known to require circuit reconfiguration, speed-based differences in locomotor rhythmogenesis have thus far not been considered. It has been posited that distinct rhythm-generating neurons control motor output at different frequencies, whereas pattern-forming neurons integrate rhythmogenic signals to produce different motor intensities. In the first part of my dissertation, I address these questions by performing whole cell current- and voltage-clamp recordings of Chx10-labeled V2a interneurons, which provide a conserved source of rhythmic premotor excitatory drive in larval zebrafish. This cell population can be divided into two morphological subtypes based on their axonal trajectories. The descending V2as have a descending main axon, whereas the bifurcating V2as have a descending axon and an additional ascending branch. Consistent with distinct roles in rhythm-generation and pattern-formation, the descending subtypes fire more selectively at fast or slow frequencies, and possess intrinsic cellular properties relevant to those frequencies, whereas the bifurcating subtypes are active over a broader frequency range, exhibit a higher recruitment reliability at all speeds and do not possess rhythmogenic properties relevant to their recruitment frequencies. Surprisingly, the rhythmic activity of both subtypes is best explained by patterns of synaptic drive regardless of intrinsic potential for rhythmogenesis. Both subtypes receive phasic excitation that is scaled to their preferred recruitment frequencies. On the other hand, inhibition to the two subtypes is organized in a cell-type and speed-specific manner. At fast speeds, the descending V2as predominantly receive reciprocal inhibition, whereas additional recurrent inhibition shapes the output of bifurcating V2as. Contrastingly, recurrent inhibition sculpts descending V2a activity at slow speeds whereas the bifurcating V2as rely solely on reciprocal inhibition. These results suggest that rhythmogenesis at different locomotor speeds is orchestrated by cell-type specific modes. In the second part of my dissertation, I explore changes in the structure and synaptic output of distinct types of V2a neurons that could explain the maintenance of fast, escape swimming behavior during a developmental window when slower locomotor circuits and coordination are maturing. In particular, motor neurons engaged during fast escapes increase in size, yet continue to be recruited, meaning there must be a mechanism to compensate for their decreased excitability. By tracking changes in the morphology and synapses of individually labeled V2a neurons at the embryonic and larval stages, I show that some V2a neurons ramify and increase synaptic output, while others prune away synaptic connections. I also provide preliminary evidence that V2a neurons stabilize existing and add more synapses onto motor neurons as zebrafish embryos mature into larvae. This suggests that increases in size are accommodated by increases in the strength of existing connections and the addition of new ones.

English

ISBN: 9798382762913Subjects--Topical Terms:

588700
Neurosciences.
Subjects--Index Terms:

Larval zebrafish

Origins of Spinal V2a Rhythmicity at Different Locomotor Speeds in Larval Zebrafish /
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500 $a Advisors: McLean, David Committee members: Gallio, Marco; Miri, Andrew; Schmidt, Tiffany.
502 $b Ph.D. $c Northwestern University $d 2024.
520 $a While locomotor rhythms are known to be generated by spinal circuits, the mechanisms underpinning this inherent capacity for rhythmogenesis remain intensely debated. It has been proposed that such locomotor rhythms are driven by intrinsic pacemakers, emergent network properties, or some combination of the two. Additionally, even though locomotion at different speeds is known to require circuit reconfiguration, speed-based differences in locomotor rhythmogenesis have thus far not been considered. It has been posited that distinct rhythm-generating neurons control motor output at different frequencies, whereas pattern-forming neurons integrate rhythmogenic signals to produce different motor intensities. In the first part of my dissertation, I address these questions by performing whole cell current- and voltage-clamp recordings of Chx10-labeled V2a interneurons, which provide a conserved source of rhythmic premotor excitatory drive in larval zebrafish. This cell population can be divided into two morphological subtypes based on their axonal trajectories. The descending V2as have a descending main axon, whereas the bifurcating V2as have a descending axon and an additional ascending branch. Consistent with distinct roles in rhythm-generation and pattern-formation, the descending subtypes fire more selectively at fast or slow frequencies, and possess intrinsic cellular properties relevant to those frequencies, whereas the bifurcating subtypes are active over a broader frequency range, exhibit a higher recruitment reliability at all speeds and do not possess rhythmogenic properties relevant to their recruitment frequencies. Surprisingly, the rhythmic activity of both subtypes is best explained by patterns of synaptic drive regardless of intrinsic potential for rhythmogenesis. Both subtypes receive phasic excitation that is scaled to their preferred recruitment frequencies. On the other hand, inhibition to the two subtypes is organized in a cell-type and speed-specific manner. At fast speeds, the descending V2as predominantly receive reciprocal inhibition, whereas additional recurrent inhibition shapes the output of bifurcating V2as. Contrastingly, recurrent inhibition sculpts descending V2a activity at slow speeds whereas the bifurcating V2as rely solely on reciprocal inhibition. These results suggest that rhythmogenesis at different locomotor speeds is orchestrated by cell-type specific modes. In the second part of my dissertation, I explore changes in the structure and synaptic output of distinct types of V2a neurons that could explain the maintenance of fast, escape swimming behavior during a developmental window when slower locomotor circuits and coordination are maturing. In particular, motor neurons engaged during fast escapes increase in size, yet continue to be recruited, meaning there must be a mechanism to compensate for their decreased excitability. By tracking changes in the morphology and synapses of individually labeled V2a neurons at the embryonic and larval stages, I show that some V2a neurons ramify and increase synaptic output, while others prune away synaptic connections. I also provide preliminary evidence that V2a neurons stabilize existing and add more synapses onto motor neurons as zebrafish embryos mature into larvae. This suggests that increases in size are accommodated by increases in the strength of existing connections and the addition of new ones.
546 $a English
590 $a School code: 0163
650 4 $a Neurosciences. $3 588700
650 4 $a Physiology. $3 518431
650 4 $a Aquatic sciences. $3 3174300
650 4 $a Developmental biology. $3 592588
650 4 $a Morphology. $3 591167
653 $a Larval zebrafish
653 $a Locomotor central pattern generators
653 $a Locomotor rhythmicity
653 $a Locomotor circuits
653 $a Rhythm generation
690 $a 0317
690 $a 0758
690 $a 0792
690 $a 0287
690 $a 0719
710 2 $a Northwestern University. $b Interdepartmental Biological Sciences (IBiS) Graduate Program. $e degree granting institution. $3 3815850
720 1 $a McLean, David $e degree supervisor.
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791 $a Ph.D.
792 $a 2024
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