Biology subjects

McLean, D. L.

Publications and source records attributed to McLean, D. L..

5 recordsLinked to original sources

bioRxiv2024

Coordinated spinal locomotor network dynamics emerge from cell-type-specific connectivity patterns

Even without detailed instruction from the brain, spinal locomotor circuitry generates coordinated behavior characterized by left-right alternation, segment-to-segment propagation, and variable-speed control. While existing models have emphasized the contributions of cellular- and network-level properties, the core mechanisms underlying rhythmogenesis remain incompletely understood. Further, neither family of models has fully accounted for recent experimental results in zebrafish and other organisms pointing to the importance of cell-type-specific intersegmental connectivity patterns and recruitment of speed-selective subpopulations of interneurons. In-formed by these experimental findings and others, we developed a hierarchy of increasingly detailed models of the locomotor network. We find that coordinated locomotion emerges in an inhibition-dominated network in which connectivity is determined by intersegmental phase relationships among interneurons and variable-speed control is implemented by recruitment of speed-selective subpopulations. Further, while structured excitatory connections are not necessary for rhythmogenesis, they are useful for increasing peak locomotion frequency, albeit at the cost of smooth transitions at intermediate frequencies, suggesting a basic computational trade-off between speed and control. Together, this family of models shows that network-level interactions are sufficient to generate coordinated, variable-speed locomotion, providing new interpretations of intersegmental excitatory and inhibitory connectivity, as well as the basic, recruitment-based mechanism of speed control.

neuroscience↗

bioRxiv2024

Cell-type-specific origins of spinal rhythmicity at different locomotor speeds in larval zebrafish

Different speeds of locomotion require heterogeneous spinal populations, but a common mode of rhythm generation is presumed to exist. Here, we explore the cellular versus synaptic origins of spinal rhythmicity at different speeds by performing electrophysiological recordings from premotor excitatory interneurons in larval zebrafish. Chx10-labeled V2a neurons are divided into at least two morphological subtypes proposed to play distinct roles in timing and intensity control. Consistent with distinct rhythm generating and output patterning functions within the spinal V2a population, we find that descending subtypes are recruited exclusively at slow or fast speeds and exhibit intrinsic cellular properties suitable for rhythmogenesis at those speeds, while bifurcating subtypes are recruited more reliably at all speeds and lack appropriate rhythmogenic cellular properties. Unexpectedly, however, phasic firing patterns during locomotion in rhythmogenic and non-rhythmogenic V2a neurons alike are best explained by distinct modes of synaptic inhibition linked to cell-type and speed. At fast speeds reciprocal inhibition in descending V2a neurons supports phasic firing, while recurrent inhibition in bifurcating V2a neurons helps pattern motor output. In contrast, at slow speeds recurrent inhibition in descending V2a neurons supports phasic firing, while bifurcating V2a neurons rely on reciprocal inhibition alone to pattern output. Our findings suggest cell-type-specific, not common, modes of rhythmogenesis generate and coordinate different speeds of locomotion.

neuroscience↗

bioRxiv2019

Intersection of motor volumes predicts the outcome of predator-prey interactions

The escape maneuvers of animals are key determinants of their survival. Consequently these maneuvers are under intense selection pressure. Current work indicates that a number of escape maneuver parameters contribute to survival including response latency, escape speed, and direction. This work has found that the relative importance of these parameters is context dependent, suggesting that interactions between escape maneuver parameters and the predatory context together determine the likelihood of escape success. However, it is unclear how escape maneuver parameters interact to contribute to escape success across different predatory contexts. To clarify these issues, we investigated the determinants of successful escape maneuvers by analyzing the responses of larval zebrafish to the attacks of dragonfly nymphs. We found that the strongest predictor of the outcome was the time needed for the nymph to reach the fishs initial position at the onset of the attack, measured from the time that the fish initiates its escape response. We show how this result is related to the intersection of the swept volume of the nymphs grasping organs with the volume containing all possible escape trajectories of the fish. By analyzing the intersection of these volumes, we compute the survival benefit of recruiting the Mauthner cell, a neuron in anamniotes devoted to producing escapes. We discuss how escape maneuver parameters interact in determining escape response. The intersection of motor volume approach provides a framework that unifies the influence of many escape maneuver parameters on the likelihood of survival.

animal behavior and cognition↗

bioRxiv2019

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 are 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.

neuroscience↗

bioRxiv2019

Distinct Spinal V2a and V0d Microcircuits Distribute Locomotor Control in Larval Zebrafish

Spinal interneurons coordinate adjustments in the rhythm and pattern of locomotor movements. Two prevailing models predict that interneurons either share or hierarchically distribute control of these key parameters. Here, we have tested each model in the coordination of swimming in larval zebrafish by circumferential excitatory V2a and commissural inhibitory V0d interneurons. We define two types of V2a neuron based on morphology, electrophysiology and connectivity. Type I V2as primarily propagate and amplify rhythmic signals biased to interneurons, while type II V2as primarily segregate and expedite patterning signals biased to motor neurons. Distributed control arises by differences in the likelihood of connections within types and the relative weights of connections between them, but not by a strict anatomical hierarchy. Heterogeneity among V0d neurons supports a similar functional distinction. Our findings provide a hybrid conceptual framework to better understand the origins of rhythm and pattern control in the spinal cord.

neuroscience↗