Modeling Neuromuscular Modulation in Aplysia. III. Interaction of Central Motor Commands and Peripheral Modulatory State for Optimal Behavior

2005 ◽  
Vol 93 (3) ◽  
pp. 1523-1556 ◽  
Author(s):  
Vladimir Brezina ◽  
Charles C. Horn ◽  
Klaudiusz R. Weiss
Keyword(s):  
Nervous System ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Functional Performance ◽  
Feeding Strategy ◽  
Neuromuscular System ◽  
Robust Performance ◽  
Neuron Firing ◽  
Variable Environment ◽  
Firing Patterns

Recent work in computational neuroethology has emphasized that “the brain has a body”: successful adaptive behavior is not simply commanded by the nervous system, but emerges from interactions of nervous system, body, and environment. Here we continue our study of these issues in the accessory radula closer (ARC) neuromuscular system of Aplysia. The ARC muscle participates in the animal's feeding behaviors, a set of cyclical, rhythmic behaviors driven by a central pattern generator (CPG). Patterned firing of the ARC muscle's two motor neurons, B15 and B16, releases not only ACh to elicit the muscle's contractions but also peptide neuromodulators that then shape the contractions through a complex network of actions on the muscle. These actions are dynamically complex: some are fast, but some are slow, so that they are temporally uncoupled from the motor neuron firing pattern in the current cycle. Under these circumstances, how can the nervous system, through just the narrow channel of the firing patterns of the motor neurons, control the contractions, movements, and behavior in the periphery? In two earlier papers, we developed a realistic mathematical model of the B15/B16-ARC neuromuscular system and its modulation. Here we use this model to study the functional performance of the system in a realistic behavioral task. We run the model with two kinds of inputs: a simple set of regular motor neuron firing patterns that allows us to examine the entire space of patterns, and the real firing patterns of B15 and B16 previously recorded in a 21/2-h-long meal of 749 cycles in an intact feeding animal. These real patterns are extremely irregular. Our main conclusions are the following. 1) The modulation in the periphery is necessary for superior functional performance. 2) The components of the modulatory network interact in nonlinear, context- and task-dependent combinations for best performance overall, although not necessarily in any particular cycle. 3) Both the fast and the slow dynamics of the modulatory state make important contributions. 4) The nervous system controls different components of the periphery to different degrees. To some extent the periphery operates semiautonomously. However, the structure of the peripheral modulatory network ensures robust performance under all circumstances, even with the irregular motor neuron firing patterns and even when the parameters of the functional task are randomly varied from cycle to cycle to simulate a variable feeding environment. In the variable environment, regular firing patterns, which are fine-tuned to one particular task, fail to provide robust performance. We propose that the CPG generates the irregular firing patterns, which nevertheless are guaranteed to give robust performance overall through the actions of the peripheral modulatory network, as part of a trial-and-error feeding strategy in a variable, uncertain environment.

Tight or Loose Coupling Between Components of the Feeding Neuromusculature of Aplysia?

2005 ◽  
Vol 94 (1) ◽  
pp. 531-549 ◽  
Author(s):  
Yuriy Zhurov ◽  
Klaudiusz R. Weiss ◽  
Vladimir Brezina
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Neuromuscular System ◽  
Loose Coupling ◽  
Tight Coupling ◽  
Feeding Behaviors ◽  
Motor Programs ◽  
Firing Patterns ◽  
Functional Behavior ◽  
Tightly Coupled

Like other complex behaviors, the cyclical, rhythmic consummatory feeding behaviors of Aplysia—biting, swallowing, and rejection of unsuitable food—are produced by a complex neuromuscular system: the animal's buccal mass, with numerous pairs of antagonistic muscles, controlled by the firing of numerous motor neurons, all driven by the motor programs of a central pattern generator (CPG) in the buccal ganglia. In such a complex neuromuscular system, it has always been assumed that the activities of the various components must necessarily be tightly coupled and coordinated if successful functional behavior is to be produced. However, we have recently found that the CPG generates extremely variable motor programs from one cycle to the next, and so very variable motor neuron firing patterns and contractions of individual muscles. Here we show that this variability extends even to higher-level parameters of the operation of the neuromuscular system such as the coordination between entire antagonistic subsystems within the buccal neuromusculature. In motor programs elicited by stimulation of the esophageal nerve, we have studied the relationship between the contractions of the accessory radula closer (ARC) muscle, and the firing patterns of its motor neurons B15 and B16, with those of its antagonist, the radula opener (I7) muscle, and its motor neuron B48. There are two separate B15/B16-ARC subsystems, one on each side of the animal, and these are indeed very tightly coupled. Tight coupling can, therefore, be achieved in this neuromuscular system where required. Yet there is essentially no coupling at all between the contractions of the ARC muscles and those of the antagonistic radula opener muscle. We interpret this result in terms of a hypothesis that ascribes a higher-order benefit to such loose coupling in the neuromusculature. The variability, emerging in the successive feeding movements made by the animal, diversifies the range of movements and thereby implements a trial-and-error search through the space of movements that might be successful, an optimal strategy for the animal in an unknown, rapidly changing feeding environment.

The Neuromuscular Transform: The Dynamic, Nonlinear Link Between Motor Neuron Firing Patterns and Muscle Contraction in Rhythmic Behaviors

2000 ◽  
Vol 83 (1) ◽  
pp. 207-231 ◽  
Author(s):  
Vladimir Brezina ◽  
Irina V. Orekhova ◽  
Klaudiusz R. Weiss
Keyword(s):  
Nervous System ◽  
Motor Neuron ◽  
Muscle Contraction ◽  
Firing Pattern ◽  
Systems Approach ◽  
Muscle Contractions ◽  
Neuron Firing ◽  
Firing Patterns ◽  
Motor Commands ◽  
Rhythmic Behaviors

The nervous system issues motor commands to muscles to generate behavior. All such commands must, however, pass through a filter that we call here the neuromuscular transform (NMT). The NMT transforms patterns of motor neuron firing to muscle contractions. This work is motivated by the fact that the NMT is far from being a straightforward, transparent link between motor neuron and muscle. The NMT is a dynamic, nonlinear, and modifiable filter. Consequently motor neuron firing translates to muscle contraction in a complex way. This complexity must be taken into account by the nervous system when issuing its motor commands, as well as by us when assessing their significance. This is the first of three papers in which we consider the properties and the functional role of the NMT. Physiologically, the motor neuron–muscle link comprises multiple steps of presynaptic and postsynaptic Ca2+ elevation, transmitter release, and activation of the contractile machinery. The NMT formalizes all these into an overall input-output relation between patterns of motor neuron firing and shapes of muscle contractions. We develop here an analytic framework, essentially an elementary dynamical systems approach, with which we can study the global properties of the transformation. We analyze the principles that determine how different firing patterns are transformed to contractions, and different parameters of the former to parameters of the latter. The key properties of the NMT are its nonlinearity and its time dependence, relative to the time scale of the firing pattern. We then discuss issues of neuromuscular prediction, control, and coding. Does the firing pattern contain a code by means of which particular parameters of motor neuron firing control particular parameters of muscle contraction? What information must the motor neuron, and the nervous system generally, have about the periphery to be able to control it effectively? We focus here particularly on cyclical, rhythmic contractions which reveal the principles particularly clearly. Where possible, we illustrate the principles in an experimentally advantageous model system, the accessory radula closer (ARC)–opener neuromuscular system of Aplysia. In the following papers, we use the framework developed here to examine how the properties of the NMT govern functional performance in different rhythmic behaviors that the nervous system may command.

The Neuromuscular Transform Constrains the Production of Functional Rhythmic Behaviors

2000 ◽  
Vol 83 (1) ◽  
pp. 232-259 ◽  
Author(s):  
Vladimir Brezina ◽  
Klaudiusz R. Weiss
Keyword(s):  
Nervous System ◽  
Motor Neuron ◽  
Preceding Paper ◽  
Limited Range ◽  
Functional Requirements ◽  
Cycle Frequency ◽  
Neuron Firing ◽  
Firing Patterns ◽  
Functional Behavior ◽  
Rhythmic Behaviors

We continue our study of the properties and the functional role of the neuromuscular transform (NMT). The NMT is an input-output relation that formalizes the processes by which patterns of motor neuron firing are transformed to muscle contractions. Because the NMT acts as a dynamic, nonlinear, and modifiable filter, the transformation is complex. In the preceding paper we developed a framework for analysis of the NMT and identified with it principles by which the NMT transforms different firing patterns to contractions. The ultimate question is functional, however. In sending different firing patterns through the NMT, the nervous system is seeking to command different functional behaviors, with specific contraction requirements. To what extent do the contractions that emerge from the NMT actually satisfy those requirements? In this paper we extend our analysis to address this issue. We define representative behavioral tasks and corresponding measures of performance, for a single neuromuscular unit, for two antagonistic units, and, in a real illustration, for the accessory radula closer (ARC)–opener neuromuscular system of Aplysia. We focus on cyclical, rhythmic behaviors which reveal the underlying principles particularly clearly. We find that, although every pattern of motor neuron firing produces some state of muscle contraction, only a few patterns produce functional behavior, and even fewer produce efficient functional behavior. The functional requirements thus dictate certain patterns to the nervous system. But many desirable functional behaviors are not possible with any pattern. We examine, in particular, how rhythmic behaviors degrade and disintegrate as the nervous system attempts to speed up their cycle frequency. This happens because, with fixed properties, the NMT produces only a limited range of contraction shapes that are kinetically well matched to the firing pattern only on certain time scales. Thus the properties of the NMT constrain and restrict the production of functional behaviors. In the following paper, we see how the constraint may be alleviated and the range of functional behaviors expanded by appropriately tuning the properties of the NMT through neuromuscular plasticity and modulation.

scholarly journals Multifaceted roles of microRNAs: From motor neuron generation in embryos to degeneration in spinal muscular atrophy

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Tai-Heng Chen ◽  
Jun-An Chen
Keyword(s):  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Muscular Atrophy ◽  
Cell Types ◽  
Spinal Motor Neurons ◽  
Potential Applications ◽  
The Central Nervous System

Two crucial questions in neuroscience are how neurons establish individual identity in the developing nervous system and why only specific neuron subtypes are vulnerable to neurodegenerative diseases. In the central nervous system, spinal motor neurons serve as one of the best-characterized cell types for addressing these two questions. In this review, we dissect these questions by evaluating the emerging role of regulatory microRNAs in motor neuron generation in developing embryos and their potential contributions to neurodegenerative diseases such as spinal muscular atrophy (SMA). Given recent promising results from novel microRNA-based medicines, we discuss the potential applications of microRNAs for clinical assessments of SMA disease progression and treatment.

Dopamine modulation of gill reflex behavior in Aplysia

1979 ◽  
Vol 57 (3) ◽  
pp. 329-332 ◽  
Author(s):  
Peter Ruben ◽  
Ken Lukowiak
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Motor Neuron ◽  
Peripheral Nervous System ◽  
Motor Neurons ◽  
Withdrawal Reflex ◽  
Dopaminergic Pathway ◽  
The Central Nervous System ◽  
Dopamine Modulation

We have studied the effects of dopamine on the gill withdrawal reflex evoked by tactile siphon stimulation in the margine mollusc Aplysia. Physiological concentrations of dopamine (diluted in seawater) were perfused through the gill during siphon stimulation series. The amplitude of the reflex was potentiated by dopamine and habituation of the reflex was prevented. This occurred with no change in the activity evoked in central motor neurons. These results lead us to conclude that the dopaminergic motor neuron L9 is modulating habituation in the periphery and that the central nervous system facilitatory control of the peripheral nervous system may act via a dopaminergic pathway.

scholarly journals “Stretch-Growth” of Motor Axons in Custom Mechanobioreactors to Generate Long-Projecting Axonal and Axonal-Myocyte Constructs

2019 ◽  
Author(s):  
Kritika S. Katiyar ◽  
Laura A. Struzyna ◽  
Suradip Das ◽  
D. Kacy Cullen
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Motor Axon ◽  
Central Feature ◽  
Motor Axons ◽  
Ganglion Neurons

AbstractThe central feature of peripheral motor axons is their remarkable lengths as they project from a motor neuron residing in the spinal cord to an often-distant target muscle. However, to date in vitro models have not replicated this central feature owing to challenges in generating motor axon tracts beyond a few millimeters in length. To address this, we have developed a novel combination of micro-tissue engineering and mechanically assisted growth techniques to create long-projecting centimeter-scale motor axon tracts. Here, primary motor neurons were isolated from the spinal cords of rats and induced to form engineered micro-spheres via forced aggregation in custom micro-wells. This three-dimensional micro-tissue yielded healthy motor neurons projecting dense, fasciculated axonal tracts. Within our custom-built mechanobioreactors, motor neuron culture conditions, neuronal/axonal architecture, and mechanical growth conditions were systematically optimized to generate parameters for robust and efficient “stretch-growth” of motor axons. We found that axons projecting from motor neuron aggregates were able to respond to axon displacement rates at least 10 times greater than that tolerated by axons projecting from dissociated motor neurons. The growth and structural characteristics of these stretch-grown motor axons were compared to benchmark stretch-grown axons from sensory dorsal root ganglion neurons, revealing similar axon densities yet increased motor axon fasciculation. Finally, motor axons were integrated with myocytes and then stretch-grown to create novel long-projecting axonal-myocyte constructs that better recreate characteristic dimensions of native nerve-muscle anatomy. This is the first demonstration of mechanical elongation of spinal cord motor axons and may have applications as anatomically inspired in vitro testbeds or as tissue engineered “living scaffolds” for targeted axon tract reconstruction following nervous system injury or disease.Significance StatementWe have developed novel axon tracts of unprecedented lengths spanning either two discrete populations of neurons or a population of neurons and skeletal myocytes. This is the first demonstration of “stretch-grown” motor axons that recapitulate the structure of spinal motor neurons in vivo by projecting long axons from a pool of motor neurons to distant targets, and may have applications as anatomically inspired in vitro test beds to study mechanisms of axon growth, development, and neuromuscular function in anatomically accurate axo-myo constructs; as well as serve as “living scaffolds” in vivo for targeted axon tract reconstruction following nervous system trauma.

Structure of the network mediating siphon-elicited siphon withdrawal in Aplysia

1995 ◽  
Vol 73 (6) ◽  
pp. 2413-2427 ◽  
Author(s):  
W. N. Frost ◽  
E. R. Kandel
Keyword(s):  
Motor Neuron ◽  
Learning And Memory ◽  
Sensory Neuron ◽  
Motor Neurons ◽  
Model System ◽  
Abdominal Ganglion ◽  
Inhibitory Interneurons ◽  
Neuron Firing ◽  
Respiratory Pumping

1. The network mediating siphon-elicited siphon withdrawal in Aplysia is a useful model system for cellular studies of simple forms of learning and memory. Here we describe three new cells in this circuit, L33, L34, and L35, and several new connections among the following network neurons: LE, L16, L29, L30, L32, L33, L34, and L35. On the basis of these findings we present an updated diagram of the network. Altogether, 100 neurons have now been identified in the abdominal ganglion that can participate in both siphon-elicited and spontaneous respiratory pumping siphon withdrawals. 2. Two features of the interneuronal population may have important behavioral functions. First, the L29 interneurons make fast and slow excitatory connections onto the LFS cells, which may be important for transforming brief sensory neuron discharges into the long-lasting motor neuron firing that underlies withdrawal duration. Second, inhibitory interneurons are prominent in the network. The specific connectivity of certain of these interneurons is appropriate to block potentially interfering inhibitory inputs from other networks during execution of the behavior. 3. Deliberate searches have so far revealed very few excitatory interneuronal inputs to the network interneurons and motor neurons within the abdominal ganglion. These results, together with intracellular studies by others, are more consistent at present with a relatively dedicated rather than a highly distributed organizational scheme for the siphon-elicited siphon withdrawal circuitry.

scholarly journals Integrins Have Cell-Type-Specific Roles in the Development of Motor Neuron Connectivity

2019 ◽  
Vol 7 (3) ◽  
pp. 17 ◽  
Author(s):  
Devyn Oliver ◽  
Emily Norman ◽  
Heather Bates ◽  
Rachel Avard ◽  
Monika Rettler ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Adhesion ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Neuron Development ◽  
Wild Type ◽  
Cell Type ◽  
C Elegans ◽  
Cell Type Specific ◽  
Two Phases

Formation of the nervous system requires a complex series of events including proper extension and guidance of neuronal axons and dendrites. Here we investigate the requirement for integrins, a class of transmembrane cell adhesion receptors, in regulating these processes across classes of C. elegans motor neurons. We show α integrin/ina-1 is expressed by both GABAergic and cholinergic motor neurons. Despite this, our analysis of hypomorphic ina-1(gm144) mutants indicates preferential involvement of α integrin/ina-1 in GABAergic commissural development, without obvious involvement in cholinergic commissural development. The defects in GABAergic commissures of ina-1(gm144) mutants included both premature termination and guidance errors and were reversed by expression of wild type ina-1 under control of the native ina-1 promoter. Our results also show that α integrin/ina-1 is important for proper outgrowth and guidance of commissures from both embryonic and post-embryonic born GABAergic motor neurons, indicating an ongoing requirement for integrin through two phases of GABAergic neuron development. Our findings provide insights into neuron-specific roles for integrin that would not be predicted based solely upon expression analysis.

scholarly journals Glia-neuron signaling mediated by two different BMP ligands impacts synaptic growth

2021 ◽  
Author(s):  
Mathieu Bartoletti ◽  
Tracy Knight ◽  
Aaron Held ◽  
Laura M. Rand ◽  
Kristi A. Wharton
Keyword(s):  
Nervous System ◽  
Neuromuscular Junction ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Neural Development ◽  
Growth Function ◽  
Bmp Signaling ◽  
Autocrine Signaling ◽  
Loss Of Function ◽  
Synaptic Growth

ABSTRACTThe nervous system is a complex network of cells whose interactions provide circuitry necessary for an organism to perceive and move through its environment. Revealing the molecular basis of how neurons and non-neuronal glia communicate is essential for understanding neural development, behavior, and abnormalities of the nervous system. BMP signaling in motor neurons, activated in part by retrograde signals from muscle expressed Gbb (BMP5/6/7) has been implicated in synaptic growth, function and plasticity inDrosophila melanogaster. Through loss-of-function studies, we establish Gbb as a critical mediator of glia to neuron signaling important for proper synaptic growth. Furthermore, the BMP2/4 ortholog, Dpp, expressed in a subset of motor neurons, acts by autocrine signaling to also facilitate neuromuscular junction (NMJ) growth at specific muscle innervation sites. In addition to signaling from glia to motor neurons, autocrine Gbb induces signaling in larval VNC glia which strongly express the BMP type II receptor, Wit. In addition to Dpp’s autocrine motor neuron signaling, Dpp also engages in paracrine signaling to adjacent glia but not to neighboring motor neurons. In one type of dorsal midline motor neuron, RP2,dpptranscription is under tight regulation, as its expression is under autoregulatory control in RP2 but not aCC neurons. Taken together our findings indicate that bi-directional BMP signaling, mediated by two different ligands, facilitates communication between glia and neurons. Gbb, prominently expressed in glia, and Dpp acting from a discrete set of neurons induce active Smad-dependent BMP signaling to influence bouton number during neuromuscular junction growth.

scholarly journals Transsynaptic interactions between IgSF proteins DIP-α and Dpr10 are required for motor neuron targeting specificity

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
James Ashley ◽  
Violet Sorrentino ◽  
Meike Lobb-Rabe ◽  
Sonal Nagarkar-Jaiswal ◽  
Liming Tan ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Surface Proteins ◽  
Partner Choice ◽  
Neuromuscular System ◽  
Synaptic Specificity ◽  
Binding Partner ◽  
Spatial Expression Pattern ◽  
Muscle Innervation ◽  
Temporal And Spatial

The Drosophila larval neuromuscular system provides an ideal context in which to study synaptic partner choice, because it contains a small number of pre- and postsynaptic cells connected in an invariant pattern. The discovery of interactions between two subfamilies of IgSF cell surface proteins, the Dprs and the DIPs, provided new candidates for cellular labels controlling synaptic specificity. Here we show that DIP-α is expressed by two identified motor neurons, while its binding partner Dpr10 is expressed by postsynaptic muscle targets. Removal of either DIP-α or Dpr10 results in loss of specific axonal branches and NMJs formed by one motor neuron, MNISN-1s, while other branches of the MNISN-1s axon develop normally. The temporal and spatial expression pattern of dpr10 correlates with muscle innervation by MNISN-1s during embryonic development. We propose a model whereby DIP-α and Dpr10 on opposing synaptic partners interact with each other to generate proper motor neuron connectivity.

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