Hillel Chiel - US grants

In the nervous systems of all animals the neurons produce electrical patterns which signal the next cell about an event. This type of communication is well documented and is still under study. Central pattern generators are known to be responsible for the production of most motor movements. In the last few years, the notion of the central pattern generator as an autonomous network producing stereotyped outputs has given way to a much more complex view. Central pattern generators are multifunctional; that is, a given network of neurons can be reorganized to produce a different pattern of activity. Dr. Hillel Chiel is doing research to understand the cellular and synaptic basis of pattern generation in neural networks. His research will entail (1) identifying interneurons involved in the feeding central pattern generator of an invertebrate, (2) analyzing their intrinsic biophysical properties and their synaptic connections in culture, and (3) reconstructing a part of the network in culture. This work is important because it will give us new knowledge about the way nerve cells communicate with each other.

9309691 Chiel In order to survive and reproduce, animals must pursue specific goals while continuously modifying their behavior in response to changing internal and environmental conditions. Over periods of hours or days, animals must choose among different mutually exclusive behaviors, such as feeding or mating. As they engage in a particular behavior over minutes or hours, they must select among different behavioral responses in order to continue to perform that behavior (e.g., rejecting an inedible piece of food in order to continue feeding). They must also rapidly alter their behavioral responses within seconds to cope with changes in the environment (e.g., biting harder on tough food). What are the neural mechanisms underlying the ability of animals to generate adaptive behavior? In order to address this question, the principal investigator proposes to study a behavioral switch in the marine mollusc Aplysia californica. Preliminary results indicate that Aplysia is capable of switching among different behavioral responses as environmental conditions change. Specifically, the animal can switch from ingestive to rejection responses if it attempts to ingest inedible material. The investigator proposes to use intracellular recording from nerve cells in vivo and in vitro (1) to identify and characterize the properties of premotor neurons and interneurons that cause the switch in the timing of the activity of these motor neurons, as well as (2) to identify and characterize the properties of sensory neurons that trigger these different patterns of activity. Using these data, he will (3) simulate and analyze the neural network responsible for the behavioral switch. These three specific aims will allow him to test different hypotheses about the neural organization of a behavioral switch: is it due to dedicated neural circuits, to a distributed neural circuit, or to circuits that have some shared and some distinct neural elements? It will also allow him to develop a more abstract description of behavioral switching, based on concepts from dynamical systems theory.***

How does the nervous system control muscles whose function changes with their mechanical context? To answer this question, Dr. Chiel is studying muscles in an animal, the marine mollusk Aplysia californica, whose biomechanics and neural control are both tractable to experimental
analysis. To test the hypothesis that the function of the muscles I1/ I3 during feeding are dependent on their mechanical context, he will study the changing position of I1/ I3 relative to other muscles in the feeding apparatus in intact, feeding animals using MRI, as well as constructing a detailed kinematic model. Using neurophysiological techniques, he will also
determine whether the nervous system of the animal exploits the context-dependent properties of the I1/I3 muscles to generate different movements during biting as opposed to swallowing.
The proposed research is likely to suggest principles that will clarify the control of context-dependent muscles in higher vertebrates as well as in invertebrates. These studies will lead to the development of novel MRI imaging techniques that may be applied to many other freely
moving biological structures. Finally, these studies suggest a richer view of motor control, in which motor patterns are not purely driven by activity of the nervous system, but are actively constructed from the dynamics of the body as well as the dynamics of the nervous system.

EIA-0130773 Randall D. Beer-Case Western Reserve-Reconfigurable and Multifunctional Behavior Pattern Generators

We propose to develop new theories and models that extend current computational frameworks by understanding and implementing the dynamically reconfigurable and multifunctional information processing architectures of biological systems. We will address this challenge through a collaborative interdisciplinary research program focusing on multifunctional neuromechanical components and their reconfiguration into multiple behavioral patterns in animals. The ultimate goal of our proposed research is to abstract general design principles that can eventually be applied in a variety of other contexts. Specifically, we propose the following four closely intertwined experimental and modeling/theoretical projects:

1)We will undertake a detailed experimental analysis of the feeding system of the mollusk Aplysia California, which dynamically reconfigures its feeding behavior in response to changing environmental circumstances, and does so through the multifuntionality of its neuromechanics. First, we will characterize the conditions under which the animal switches between distant behavioral patterns. Second, we will examine the neural and mechanical basis of these switches.

2)We will create and analyze models of behavioral pattern switching as the basis for new design principles. First, we will construct interconnected semi-Markov models to capture behavioral pattern reconfiguration observed in biological systems. Second, we will pursue the development of a systematic design methodology for engineered systems, with potential applications to robotic assembly.

3)We will create and analyze models of multifunctional pattern generations in order to identify general design principles. First, we will use genetic algorithms to evolve multifunctional neural pattern generators that can switch between distinct behavioral patterns. Second, we will undertake a detailed study of the "design space" of these model pattern generators.

4)We will explore the implementation of multifunctional neural pattern generators in analog VLSI. First, we will develop compact, low-power pattern generators based on the experimental and theoretical work proposed above. Second, we will study the effects of noise and component mismatch on the performance of these networks.

Some small networks of neurons are remarkable for their ability to execute multiple functions. It has been a challenge to understand what the rules are for integrating feedback into features such as phase relationships among the firing patterns of active neurons, and how a small network can 'switch' from one characteristic behavior to another. Although research is clarifying the cellular and molecular mechanisms of learning, it has been more difficult to understand how changes in the properties of individual neurons change the activity of a whole neural circuit, and in turn alter an animal's overall behavior. This project is a collaboration using computational, theoretical and experimental approaches to analyze the feeding behavior of a marine mollusk, the sea hare Aplysia. This animal ingests food with rhythmic rasping and sucking motions of a jawless buccal mass, run by a network of about 130 motor neurons and interneurons; if potential food is sensed by its physical properties as inedible, the pattern of muscle activity changes from ingestion to food rejection. The overall goal is to determine how small changes in the properties of individual nerve cells create the large changes in feeding behavior that are observed after learning. Specific Aim 1 is to construct a kinetic mathematical model of the buccal mass (finite-element method), its neural control (continuous-time recurrent neural network (CTRNN), with Hodgkin-Huxley models for motor and sensory neurons), and inedible food, and to conduct experimental studies to improve the understanding of each of these components of the model. The focus of this modeling is to reproduce the changes in motor pattern observed during repeated encounters with inedible food. Specific Aim 2 is to develop a numerically optimal controller for the new kinetic model, and use it to predict the effects of small changes in timing, phasing and intensity of neural input on the behavior generated by the buccal mass. The focus here is on how the biomechanics of the periphery influences the design properties of the neural controller. The models developed in Specific Aims 1 and 2 will be used to analyze the contributions of individual neurons to the shifting coalitions that stabilize the rhythmic behavior, and to predict the importance of local changes in synaptic strengths or intrinsic properties to the overall dynamics of the neural circuit both in isolation and when it is connected to the biomechanical model. Under Specific Aim 3, experimental studies will be designed to test these predictions from simulation studies. These experimental studies will record neural activity in intact animals as they learn that food is inedible, and in reduced preparations (that show feeding-like movements) after perturbations of the activity of specific nerve cells.

This work will have an impact beyond computational neuroscience and behavioral neuroscience, to invertebrate physiology, engineering, robotics and control systems. First, it is likely to generate principles for understanding the effects of localized changes in neural activity on an animal's overall behavior. Second, it may suggest design principles for devices that can persistently pursue a specific goal despite distracting inputs, and at the same time be remarkably flexible and change behavior if an appropriate stimulus occurs in the correct context. . Third, these principles are likely to serve as the basis for novel biologically-inspired robotic and control devices. In addition, students and collaborators will be involved together in cross-disciplinary approaches and techniques that will enhance training for the next generation of scientists.

DESCRIPTION (provided by applicant): Motor systems are multifunctional, i.e., the same peripheral structures can generate qualitatively different behaviors. Diseases of the nervous system, such as stroke, severely compromise multifunctionality. To treat such diseases, it is important to understand multifunctionality in the intact nervous system. Principles of multifunctionality could also be used to construct flexible prosthetic devices. This is the rationale for analyzing multifunctionality in the marine mollusk Aplysia californica, whose biomechanics and neural control can both be studied. Kinematic measurements in intact, behaving animals of Aplysia's feeding muscles using magnetic resonance imaging have clarified the biomechanical basis of multifunctionality. The kinematics of the muscles, and in vivo recordings of neural activity correlated with the kinematics, indicate how activity in motor pools controlling buccal mass muscles must be altered to generate different feeding responses. Furthermore, these data suggest that multifunctionality of feeding in Aplysia is mediated by differential activation of context dependent identified interneurons that cause some of the observed shifts in timing, intensity and duration of the motor neuronal pools controlling muscles of the buccal mass to generate appropriate movements for qualitatively different feeding responses. To test this hypothesis, three Specific Aims will be pursued. First, we will simultaneously characterize the in vivo activity of interneurons and selected motor neurons that control the buccal muscles. Second, we will study reduced preparations capable of generating feeding motor patterns, and examine the effect of hyperpolarizing or depolarizing interneurons on the resulting motor patterns. Third, we will test the hypothesis in vivo using a novel electrophysiological technique that will allow us to turn on or turn off the activity of different interneurons in intact, behaving animals. These studies will lead to a deeper understanding of the neuromechanical principles underlying multifunctionality.

0652043
Tabib-Azar
The main objective of this research is to design and implement an array of sensing and stimulating electrodes with integrated low-power electronics and telemetry to study dynamics of the nervous system in intact and behaving animals. A minimally intrusive implantable electrode array capable of recording and stimulating at multiple sites in the nervous system will be used. An experimental preparation in which the dynamics of the nervous system (i.e., the activity in single nerve cells) can be readily related to its overall behavior will be used. The novelty of the proposed system is that it will make it possible to record and control neural activity simultaneously through a remote computer interface. In turn, this will allow novel studies of neurodynamics, since it will be possible to examine the response of the nervous system to specific stimuli. For this reason, the electrode array system will be developed for a biological organism whose neural control and biomechanics have been very well characterized, the marine mollusk Aplysia californica. Results of this research will ultimately have broader applications in human neural prostheses.

The design and fabrication of an 8x8 stimulation and sensing electrode array with different electrode geometries and coating materials to optimize recording and stimulation of many Aplysia neurons simultaneously is proposed. In parallel, design and implementation of a low-power data acquisition and telemetry electronics will take place. These devices will be tested separately and together, forming the sense/stimulate telemetry system in vitro and in vivo in isolated ganglia, semi-intact preparations and in intact and behaving animals.

Animals as simple as cockroaches and slugs and as complex as humans all possess similar ways to control how they walk, crawl, swim or fly through earth's many complex environments. Engineers have turned to these natural systems for inspiration in developing robots, hoping to attain the same ease of movement and ability to adapt to any environment on earth (or off of it). The goals of animal motion studies and robotics are clearly complementary and benefit greatly from extended interaction. Although many meetings have limited sessions dedicated to such discussions, the International Symposium on Adaptive Motion in Animals and Machines (AMAM) is uniquely dedicated to intense week long interaction among engineers and biologists. The funds from this proposal will be used to bring young U.S. scientists and engineers (especially female and underrepresented minorities) to AMAM 2008 this June 1-6 at Case Western Reserve University in Cleveland, Ohio. Funds will also be used to support web-based distribution of the meeting to members of the international community and educators who cannot attend the meeting in person. The potential impacts of this meeting include: 1) use of robots as hardware models to promote a greater understanding of how animals (including humans) control their movement through their complex worlds, 2) creation of new walking, crawling, swimming and flying robots that more closely capture properties of animals, and 3) introduction of young developing scientists and engineers to an area of research that relies heavily on collaboration of people with many different skills from many different areas for success. The ultimate goal of this work is to provide highly functional robotic devices to serve human needs, such as search and rescue, environmental monitoring, surveying and many others, as well as greater understanding of animal movement.

Walking, swimming, flying, burrowing and chewing are rhythmic behaviors that allow animals to survive and reproduce. These behaviors remain effective even in the presence of unexpected perturbations or noise. The investigators hypothesize that the robustness of a pattern generator is primarily mediated by the interplay of neural dynamics and sensory input. This hypothesis will be tested by (1) studying in vivo responses of a feeding pattern generator to mechanical perturbations in the marine mollusk Aplysia californica, whose identified neurons and well-studied biomechanics make it especially experimentally tractable, (2) using theoretical, computational and mathematical tools to develop insight into dynamical architectures of robustness, such as a globally stable limit cycles, or stable heteroclinic channels and (3) directly testing the central hypothesis using a semi-intact preparation that can generate behavior, and can respond to mechanical perturbations, to determine the role of identified sensory neurons in generating appropriate responses to these perturbations by selectively activating or inhibiting the neurons.

Developing an understanding of robust dynamical architectures would have many applications. In particular, the research will open up the possibility of creating control architectures for robots that can flexibly cope with unpredictable environmental changes, and successfully pursue long-term goals despite environmental perturbations. It will play an important role in developing robust prosthetic devices that cope flexibly with everyday tasks, simplifying the process of rehabilitation. Additionally, this project enhances the efforts of the lead investigator, a neurobiologist, and the co-investigator, a mathematician, to co-mentor students in the interdisciplinary area of mathematical and computational neuroscience, and also impacts the content of the interdisciplinary courses that they teach.

How can intelligent control be created for autonomous robots that will allow them to respond flexibly and adaptively to changing environments? In the animal world, relatively simple animals such as soft-bodied invertebrates, are capable of coordinating their many possible movements, flexibly shifting and sequencing multiple behaviors as conditions change, and learning to alter their behavior based on experience. For robots, however, this remains a challenge, which is addressed in this project using a novel control architecture that can produce sensory driven or cyclic movements.

Traditional control architectures for robotics have three layers: high level deliberative planning, low-level reactive control, and an intermediate level for sequencing and simple decision-making. Creating intermediate level controllers for intelligent behavior is particularly challenging, and a major obstacle to progress in autonomous robotics. This problem will be addressed using a novel neural-inspired control architecture, stable heteroclinic channels (SHCs) that can flexibly and robustly orchestrate multiple degrees of freedom for multifunctionality, and can readily handle behavioral hierarchies, temporal decision-making, and learning. Their properties also allow them to incorporate some of the best aspects of the two traditional approaches to robotic control: finite state machines and central pattern generator (limit cycle) controllers. SHC-based dynamical architectures underlying multifunctionality will be analyzed in a soft-bodied animal that is tractable to experimentation, and principles from these neurobiological architectures will be used to implement multifunctional behavior in a novel hyper-redundant, soft-bodied robot platform.

There are many possible applications for adaptive, flexibly-controlled soft-bodied, or hyper-redundant, robots that are able to coordinate their many degrees of freedom in varying ways to accomplish multiple functions. A multifunctional worm-like robot could crawl through pipes of varying diameter and at any angle with respect to gravity and make sharp turns at intersections. A hollow hyper-redundant robot could inspect water mains from the inside, without interrupting water flow. Such a robot could be used for oil and gas pipeline inspections to avoid costly and environmentally disastrous leaks. Smaller versions could be developed for endoscopic diagnosis of the gastrointestinal tract. The proposed work will lead to a single controller framework that can robustly coordinate multiple coupled actuated mechanisms within a robot, and describe the sequencing of distinct behaviors in both animals and robots.

This project focuses on the neural and biomechanical principles that result in dynamic stability during locomotion. Medical treatments and diagnosis for neurological conditions that affect balance and coordination (e.g. spinal cord injury, stroke, Parkinson's) can be improved with a better understanding of mammalian spinal cord circuits. Neuromechanical models will also inspire improvements to the design of mechanical systems and controllers for assistive exoskeletons for human stability and mobility. For example, such a neural model could be effective for controlling a person's muscles in tandem with control of an exoskeleton's motors and with the person's intact systems. Control systems derived from this work may also provide autonomous legged robots greater mobility and adaptability for movement in unknown terrain. This project will also involve international collaboration and interdisciplinary education and training at the intersection of neurobiology, zoology, mechanical engineering, and system control.

To better understand how the mammalian nervous system processes multi-sensory feedback for dynamic control of the many degrees of freedom in the rear legs, the investigators will: 1) Use simultaneous two-plane X-ray videography, force plates and EMG recordings to measure the kinematics, ground reaction forces, and muscle activations of rats running in various environments (treadmills of different speeds and flexibility, and on substrates with unexpected disturbances such as holes, a trapdoor and a shifting ground condition); 2) Use these data to expand a sagittal plane biomechanical model and conductance-based neural model of the rat to produce self-supporting walking of the hind legs in three dimensions; and 3) Investigate mechanisms for control of synergistic muscle groups by exploring different organizational models and testing the capability of these models for adapting to perturbations and maintaining dynamic control of walking behavior.

A companion project is being funded by the Federal Ministry of Education and Research, Germany (BMBF).

Despite the apparent differences between animals and their behaviors, they all are subject to the same constraints. All animals use a nervous system to control their motions, which must follow the laws of physics. Therefore, this NeuroNex Research Network seeks to understand how animals move by studying animals of different sizes and with unique evolutionary histories: Vertebrates (mice, rats, and cats), mollusks (sea hares), and insects (fruit flies). The differences between these species will inform how physics and evolution have shaped the nervous system. Understanding motion across different organisms and scales may lead to robots with more graceful, coordinated motion. Additionally, this Network enhances the training of American engineers and scientists by exchanging post-doctoral trainees and students between laboratories, providing them opportunities to work with different model organisms, and broadening the trainees? education. The activities of this Network enrich existing outreach programs through interactions with international, interdisciplinary collaborators and allow for new, larger initiatives. Public demonstrations, day camps, and internships carried out as part of this project expose K-12 students to interdisciplinary research and international collaborators? ideas and culture. This Network also constructs exhibits at natural science museums in its major cities and develops an interactive website describing how very different animals solve similar problems.

Animals move to seek food, mates, and shelter. In the phyla Arthropoda, Mollusca, and Chordata, the nervous system cephalized towards a higher-level brain and lower-level sensorimotor network. The brain would not exist without a body, and yet little is understood about how the nervous system controls and coordinates distributed body parts. Many fundamental questions remain unanswered: How is neural information encoded and communicated? How does the system correct for environmental perturbations? How do passive biomechanics affect the neuronal control of behavior? This leads to the foundational question: How do nervous systems control and execute interactions with the environment? This international Network of interdisciplinary research groups consists of modelers, engineers, and experimentalists to explore the Communication, Coordination, and Control of Neuromechanical Systems (C3NS). This NeuroNex Network investigates a foundational question in model genera from three phyla: adult Drosophila from Arthropoda, Aplysia from Mollusca, and small mammals from Chordata. Each interdisciplinary research group studies the control of a behavior in which the body interacts with the environment. Investigators explore how higher-level command centers (HLCCs) generate descending commands to lower-level motor centers (LLMCs), how LLMCs control the body to produce desired behavior, and how LLMCs generate ascending signals back to HLCCs. The animal models of C3NS allow the investigation of these questions across degrees of nervous system complexity and ranges of dynamic scale (i.e., size and speed) using the same conceptual modeling framework. This effort will create a bottom-up theory for how nervous systems control movement during environmental interactions. This project is co-funded by Emerging Frontiers in the Directorate for Biological Sciences and Robust Intelligence in the Directorate for Computer and Information Science and Engineering.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.