Are central pattern generators understandable?

Abstract Most rhythmic behaviors are produced by a specialized ensemble of neurons found in the central nervous system. These central pattern generators (CPGs) have become a cornerstone of neuronal circuit analysis. Studying simple invertebrate nervous systems may reveal the interactions of the neurons involved in the production of rhythmic motor output. There has recently been progress in this area, but due to certain intrinsic features of CPGs it is unlikely that present techniques will ever yield a complete understanding of any but the simplest of them. The chief impediment seems to be our inability to identify and characterize the total interneuronal pool making up a CPG. In addition, our general analytic strategy relies on a descriptive, reductionist approach, with no analytical constructs beyond phenomenological modeling. Detailed descriptive data are usually not of sufficient depth for specific model testing, giving rise instead to ad hoc explanations of mechanisms which usually turn out to be incorrect. Because they make too many assumptions, modeling studies have not added much to our understanding of CPCs; this is due not so much to inadequate simulations as to the poor quality and incomplete nature of the data provided by experimentalists. A basic strategy that would provide sufficient information for neural modeling would include: (1) identifying and characterizing each element in the CPG network; (2) specifying the synaptic connectivity between the elements; and (3) analyzing nonlinear synaptic properties and interactions by means of the connectivity matrix. Limitations based on our present technical capabilities are also discussed.

[1]  W. Mcdougall THE NATURE OF INHIBITORY PROCESSES WITHIN THE NERVOUS SYSTEM. , 1903 .

[2]  T. Brown The intrinsic factors in the act of progression in the mammal , 1911 .

[3]  T. Brown On the nature of the fundamental activity of the nervous centres; together with an analysis of the conditioning of rhythmic activity in progression, and a theory of the evolution of function in the nervous system , 1914, The Journal of physiology.

[4]  N. Bohr Light and Life , 1933, Nature.

[5]  E. Holst Die relative Koordination , 1939 .

[6]  W. Hard,et al.  The pyramidal tract; effect of maximal injury on acid phosphatase content in neurons of cats. , 1946, Journal of neurophysiology.

[7]  K. D. Roeder,et al.  Organization of the ascending giant fiber system in the cockroach, Periplaneta americana. , 1948, The Journal of experimental zoology.

[8]  William Rowan,et al.  The Study of Instinct , 1953 .

[9]  H. Evans The Study of Instinct , 1952 .

[10]  Burns Bd,et al.  Repetitive firing of respiratory neurones during their burst activity. , 1960 .

[11]  B. Burns,et al.  Repetitive firing of respiratory neurones during their burst activity. , 1960, Journal of neurophysiology.

[12]  Donald M. Wilson The Central Nervous Control of Flight in a Locust , 1961 .

[13]  J. Eccles,et al.  Inhibitory Phasing of Neuronal Discharge , 1962, Nature.

[14]  L. D. Harmon Neuromimes: Action of a Reciprocally Inhibitory Pair , 1964, Science.

[15]  G SZEKELY,et al.  LOGICAL NETWORK FOR CONTROLLING LIMB MOVEMENTS IN URODELA. , 1965, Acta physiologica Academiae Scientiarum Hungaricae.

[16]  George P. Moore,et al.  A DEFENSE OF NEURAL MODELLING , 1965 .

[17]  G. Wendler The co-ordination of walking movements in arthropods. , 1966, Symposia of the Society for Experimental Biology.

[18]  A. Lundberg,et al.  The effect of DOPA on the spinal cord. 6. Half-centre organization of interneurones transmitting effects from the flexor reflex afferents. , 1967, Acta physiologica Scandinavica.

[19]  B. Hille The Selective Inhibition of Delayed Potassium Currents in Nerve by Tetraethylammonium Ion , 1967, The Journal of general physiology.

[20]  G. P. Moore,et al.  Neuronal spike trains and stochastic point processes. I. The single spike train. , 1967, Biophysical journal.

[21]  A. Lundberg,et al.  The effect of DOPA on the spinal cord. 5. Reciprocal organization of pathways transmitting excitatory action to alpha motoneurones of flexors and extensors. , 1967, Acta physiologica Scandinavica.

[22]  G. P. Moore,et al.  Neuronal spike trains and stochastic point processes. II. Simultaneous spike trains. , 1967, Biophysical journal.

[23]  J. Salánki,et al.  Neurobiology of Invertebrates , 1968, Springer US.

[24]  B. O. Alving Spontaneous Activity in Isolated Somata of Aplysia Pacemaker Neurons , 1968, The Journal of general physiology.

[25]  H. Petsche,et al.  The firing pattern of septal neurons and the form of the hippocampal theta wave. , 1968, Brain research.

[26]  Donald M. Wilson,et al.  Models for the generation of the motor output pattern in flying locusts , 1968 .

[27]  G. Hoyle,et al.  Centrally Generated Nerve Impulse Sequences determining Swimming Behaviour in Tritonia , 1969, Nature.

[28]  M. D. Egger,et al.  A reappraisal of reflex stepping in the cat , 1969, The Journal of physiology.

[29]  K. Leibovic Information Processing in The Nervous System , 1969, Springer Berlin Heidelberg.

[30]  K. Leibovic Information Processing in The Nervous System , 1969, Springer Berlin Heidelberg.

[31]  E M Harth,et al.  Dynamics of neural structures. , 1970, Journal of theoretical biology.

[32]  E. Kandel Nerve cells and behavior. , 1970, Scientific American.

[33]  E M Harth,et al.  Brain functions and neural dynamics. , 1970, Journal of theoretical biology.

[34]  P. Klinge The Coming of the Golden Age: A View of the End of Progress Gunther S. Stent , 1970 .

[35]  D. Maynard,et al.  Recordings from the stomatogastric nervous system in intact lobsters , 1970 .

[36]  D. Kennedy Nerve cells and behavior. , 1971, American scientist.

[37]  M. Mendelson Oscillator Neurons in Crustacean Ganglia , 1971, Science.

[38]  A. Selverston,et al.  Neural geometry and activation of crayfish fast flexor motoneurons. , 1972, Journal of neurophysiology.

[39]  M. S. Berry A system of electrically coupled small cells in the buccal ganglia of the pond snail Planorbis corneus. , 1972, The Journal of experimental biology.

[40]  M. Spira,et al.  Synaptic control of electrotonic coupling between neurons. , 1972, Brain research.

[41]  P. Dettmar [Using the Fick's shifting hypothesis to explain dyschromatopsia in a model computation for data processing of disordered colored vision in man]. , 1972, Kybernetik.

[42]  F. Krasne,et al.  The organization of escape behaviour in the crayfish. , 1972, The Journal of experimental biology.

[43]  J. Cowan,et al.  Excitatory and inhibitory interactions in localized populations of model neurons. , 1972, Biophysical journal.

[44]  G L Gerstein,et al.  Mutual temporal relationships among neuronal spike trains. Statistical techniques for display and analysis. , 1972, Biophysical journal.

[45]  C. Levinthal,et al.  Structure and development of neuronal connections in isogenic organisms: variations and similarities in the optic system of Daphnia magna. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[46]  M. I. Phillips Brain unit activity during behavior , 1973 .

[47]  K. Brändle,et al.  The control of alternating coordination of limb pairs in the newt (Triturus vulgaris). , 1973, Brain, behavior and evolution.

[48]  Theodosios Pavlidis,et al.  Biological Oscillators: Their Mathematical Analysis , 1973 .

[49]  S. B. Kater,et al.  Integration of sensory and centrally programmed components in generation of cyclical feeding activity of Helisoma trivolvis. , 1973, Journal of neurophysiology.

[50]  E. Harth,et al.  Stationary states and transients in neural populations. , 1973, Journal of theoretical biology.

[51]  G. Hoyle,et al.  The neuronal basis of behavior in Tritonia. 3. Neuronal mechanism of a fixed action pattern. , 1973, Journal of neurobiology.

[52]  G. Hoyle,et al.  The neuronal basis of behavior in Tritonia. IV. The central origin of a fixed action pattern demonstrated in the isolated brain. , 1973, Journal of neurobiology.

[53]  F. G. Worden,et al.  The neurosciences : third study program , 1974 .

[54]  P. A. Getting,et al.  Modification of neuron properties by electrotonic synapses. II. Burst formation by electrotonic synapses. , 1974, Journal of neurophysiology.

[55]  W. Kristan Neural Control of Swimming in the Leech , 1974 .

[56]  D. Perkel,et al.  Motor Pattern Production in Reciprocally Inhibitory Neurons Exhibiting Postinhibitory Rebound , 1974, Science.

[57]  H. Gainer,et al.  Peptide Regulation of Bursting Pacemaker Activity in a Molluscan Neurosecretory Cell , 1974, Science.

[58]  E. Kandel,et al.  Neural control of circulation in Aplysia. II. Interneurons. , 1974, Journal of neurophysiology.

[59]  S. B. Kater,et al.  Feeding in Helisoma trivolvis: The Morphological and Physiological Bases of a Fixed Action Pattern , 1974 .

[60]  etc.,et al.  Dynamic Patterns of Brain Cell Assemblies , 1974 .

[61]  G. Hoyle Identified neurons and the future of neuroethology , 1975 .

[62]  M. Reivich,et al.  Mapping of functional neural pathways by autoradiographic survey of local metabolic rate with (14C)deoxyglucose. , 1975, Science.

[63]  D. Hubel,et al.  Mode of termination of retinotectal fibers in macaque monkey: An autoradiographic study , 1975, Brain Research.

[64]  D. Perkel,et al.  Nerve-impulse patterns: A quantitative display technique for three neurons , 1975, Brain Research.

[65]  M. Burrows Co-ordinating interneurones of the locust which convey two patterns of motor commands: their connexions with flight motoneurones. , 1975, The Journal of experimental biology.

[66]  C. R. Fourtner,et al.  Nonspiking interneurons in walking system of the cockroach. , 1975, Journal of neurophysiology.

[67]  Co-ordinating interneurones of the locust which convey two patterns of motor commands: their connexions with ventilatory motoneurones. , 1975, The Journal of experimental biology.

[68]  P. A. Getting Tritonia swimming: triggering of a fixed action pattern , 1975, Brain Research.

[69]  H. Gainer,et al.  Studies on bursting pacemaker potential activity in molluscan neurons. III. Effects of hormones , 1975, Brain Research.

[70]  M. Burrows Monosynaptic connexions between wing stretch receptors and flight motoneurones of the locust. , 1975, The Journal of experimental biology.

[71]  E. Harth,et al.  The escape of Tritonia: dynamics of a neuromuscular control mechanism. , 1975, Journal of theoretical biology.

[72]  The Synaptic Organization of the Brain: An Introduction , 1975 .

[73]  J. Vibert,et al.  Three dimensional representation of bulbo-pontine respiratory networks architecture from unit density maps , 1976, Brain Research.

[74]  M. S. Berry,et al.  Criteria for distinguishing between monosynaptic and polysynaptic transmission , 1976, Brain Research.

[75]  D. Humphrey,et al.  Dynamic patterns of brain cell assemblies , 1976 .

[76]  M. Spira,et al.  Electrotonic coupling: effective sign reversal by inhibitory neurons. , 1976, Science.

[77]  D. Hartline,et al.  Simulation of network activity in stomatogastric ganglion of the spiny lobster, panulirus , 1976, Brain Research.

[78]  P. Dev,et al.  Electrotonic processing of information by brain cells. , 1976, Science.

[79]  R. Drucker-Colín,et al.  Is there a sleep transmitter? , 1976, Progress in Neurobiology.

[80]  William J. Davis,et al.  Organizational Concepts in the Central Motor Networks of Invertebrates , 1976 .

[81]  E. Kandel Cellular basis of behavior: An introduction to behavioral neurobiology. , 1976 .

[82]  S. Grillner,et al.  Some Aspects on the Descending Control of the Spinal Circuits Generating Locomotor Movements , 1976 .

[83]  G. Székely,et al.  Organization of Locomotion , 1976 .

[84]  Ludvík Prouza,et al.  On the weight matrices of linear difference equations , 1976, Kybernetika.

[85]  P. Stein Mechanisms of Interlimb Phase Control , 1976 .

[86]  A. Selverston Neuronal Mechanisms for Rhythmic Motor Pattern Generation in a Simple System , 1976 .

[87]  J. C. Fentress Simpler networks and behavior , 1976 .

[88]  A. Selverston,et al.  The stomatogastric nervous system: Structure and function of a small neural network , 1976, Progress in Neurobiology.

[89]  J. H. Schwartz,et al.  Functional constancy in Aplysia nervous systems with anomalously duplicated identified neurons , 1976, Brain Research.

[90]  K. R. Weiss,et al.  Homology of the giant serotonergic neurons (metacerebral cells) in Aplysia and pulmonate molluscs , 1976, Brain Research.

[91]  A. Willows Trigger Neurons in the Mollusk Tritonia , 1976 .

[92]  T. Tameyasu Intracellular potentials in the small cells and cellular interaction in the cardiac ganglion of the lobster Panulirus japonicus. , 1976, Comparative biochemistry and physiology. A, Comparative physiology.

[93]  W. O. Friesen,et al.  An oscillatory neuronal circuit generating a locomotory rhythm. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[94]  Daniel S. Ruchkin,et al.  Principles of Neurobiological Signal Analysis , 1976 .

[95]  F. Delcomyn An approach to the study of neural activity during behaviour in insects. , 1976, Journal of insect physiology.

[96]  J. C. Fentress THE TONIC HYPOTHESIS AND THE PATTERNING OF BEHAVIOR * , 1977, Annals of the New York Academy of Sciences.

[97]  A. Selverston,et al.  Synaptic control of an endogenous pacemaker network. , 1977, Journal de physiologie.

[98]  FRED DELCOMYN,et al.  Corollary discharge to cockroach giant interneurones , 1977, Nature.

[99]  H. Aréchigá Circadian rhythmicity in the nervous system of crustaceans. , 1977, Federation proceedings.

[100]  John M. Hollerbach A Simple Model for Handwriting , 1977, IJCAI.

[101]  A. Grinvald,et al.  Simultaneous recording from several neurones in an invertebrate central nervous system , 1977, Nature.

[102]  Siegler Mv Motor neurone coordination and sensory modulation in the feeding system of the mollusc Pleurobranchaea californica. , 1977 .

[103]  A. Winfree Phase control of neural pacemakers. , 1977, Science.

[104]  Grégoire Nicolis,et al.  Self-Organization in nonequilibrium systems , 1977 .

[105]  H. Pinsker Aplysia bursting neurons as endogenous oscillators. II. Synchronization and entrainment by pulsed inhibitory synaptic input. , 1977, Journal of neurophysiology.

[106]  H. Pinsker Aplysia bursting neurons as endogenous oscillators. I. Phase-response curves for pulsed inhibitory synaptic input. , 1977, Journal of neurophysiology.

[107]  S. Kater,et al.  Identified higher-order neurons controlling the feeding motor program of helisoma , 1977, Neuroscience.

[108]  M. Siegler Motor neurone coordination and sensory modulation in the feeding system of the mollusc Pleurobranchaea californica. , 1977, The Journal of experimental biology.

[109]  W. N. Ross,et al.  Optical recording of neuronal activity in an invertebrate central nervous system: simultaneous monitoring of several neurons. , 1977, Journal of neurophysiology.

[110]  B. Cohen Cellular Basis of Behavior , 1977, Neurology.

[111]  T Pavlidis,et al.  Oscillator theory and neurophysiology: introduction. , 1977, Federation proceedings.

[112]  M. Konishi,et al.  Neural control of behavior. , 1978, Annual review of neuroscience.

[113]  S. B. Kater,et al.  Centrally programmed feeding in helisoma: Identification and characteristics of an electrically coupled premotor neuron network , 1978, Brain Research.

[114]  M. Sanders Control of Gaze by Brain Stem Neurons , 1978 .

[115]  G. Wendler Lokomotion: Das Ergebnis zentral-peripherer Interaktion , 1978 .

[116]  S. B. Kater,et al.  Burst generation by electrically coupled network in the snail Helisoma: Analysis using computer simulation , 1978, Brain Research.

[117]  H. Pinsker,et al.  In vivo responses of paired giant mechanoreceptor neurons in Aplysia abdominal ganglion. , 1978, Journal of neurobiology.

[118]  W. Kristan,et al.  Initiation, Maintenance and Modulation of Swimming in the Medicinal Leech by the Activity of a Single Neurone , 1978 .

[119]  F. Magni,et al.  Patterns of activity and the effects of activation of the fast conducting system on the behaviour of unrestrained leeches. , 1978, The Journal of experimental biology.

[120]  A. Grinvald,et al.  Optical methods for monitoring neuron activity. , 1978, Annual review of neuroscience.

[121]  W. O. Friesen,et al.  Neural circuits for generating rhythmic movements. , 1978, Annual review of biophysics and bioengineering.

[122]  K. R. Weiss,et al.  The command neuron concept , 1978, Behavioral and Brain Sciences.

[123]  I. Kupfermann,et al.  Modulatory control of buccal musculature by a serotonergic neuron (metacerebral cell) in Aplysia. , 1978, Journal of neurophysiology.

[124]  George L. Gerstein,et al.  Identification of functionally related neural assemblies , 1978, Brain Research.

[125]  D. F. Russell,et al.  Bursting neural networks: a reexamination. , 1978, Science.

[126]  C. Goodman Isogenic grasshoppers: Genetic variability in the morphology of identified neurons , 1978, The Journal of comparative neurology.

[127]  M. Kovac,et al.  Command neurons in Pleurobranchaea receive synaptic feedback from the motor network they excite. , 1978, Science.

[128]  J. Truman Hormonal Release of Stereotyped Motor Programmes from the Isolated Nervous System of the Cecropia Silkmoth , 1978 .

[129]  J. Byrne,et al.  Respiratory pumping: Neuronal control of a centrally commanded behavior in aplysia , 1978, Brain Research.

[130]  H. Pinsker,et al.  Neuronal correlates of siphon withdrawal in freely behaving Aplysia. , 1979, Journal of neurophysiology.

[131]  H. Pinsker,et al.  Computer separation of unitary spikes from whole-nerve recordings , 1979, Brain Research.

[132]  M. Burrows Synaptic potentials effect the release of transmitter from locust nonspiking interneurons. , 1979, Science.

[133]  E. Peterson,et al.  Do circadian oscillators ever stop in constant light? , 1979, Nature.

[134]  R. Chase The mentalist hypothesis and invertebrate neurobiology. , 1979, Perspectives in biology and medicine.

[135]  Gail A. Carpenter,et al.  Bursting Phenomena in Excitable Membranes , 1979 .

[136]  R. Calabrese,et al.  The roles of endogenous membrane properties and synaptic interaction in generating the heartbeat rhythm of the leech, Hirudo medicinalis. , 1979, The Journal of experimental biology.

[137]  K. Pearson,et al.  Correlation of variability in structure with variability in synaptic connections of an identified interneuron in locusts , 1979, The Journal of comparative neurology.

[138]  S. Basinger,et al.  Differential labelling of retinal neurones by 3H-2-deoxyglucose , 1979, Nature.

[139]  L. Fiore,et al.  Electrotonic and chemical connections among small cells in the buccal ganglion of Aplysia. , 1979, Archives italiennes de biologie.

[140]  D. A. Dorsett,et al.  The Integration of the Patterned Output of Buccal Motoneurones During Feeding in Tritonia Hombergi , 1979 .

[141]  J. Miller,et al.  Rapid killing of single neurons by irradiation of intracellularly injected dye. , 1979, Science.

[142]  J. Raper Nonimpulse-mediated synaptic transmission during the generation of a cyclic motor program. , 1979, Science.

[143]  S. Treistman Duplication of a spontaneously active neuron in Aplysia: electrical coupling and effects of a phosphodiesterase inhibitor. , 1979, Journal of neurobiology.

[144]  C. Rovainen Neurobiology of lampreys. , 1979, Physiological reviews.

[145]  C. Antzelevitch,et al.  Phase resetting and annihilation of pacemaker activity in cardiac tissue. , 1979, Science.

[146]  P. Holmes,et al.  Bifurcation of periodic motions in two weakly coupled van der Pol oscillators , 1980 .

[147]  F. Delcomyn Neural basis of rhythmic behavior in animals. , 1980, Science.

[148]  H. Pinsker,et al.  Information Processing in the Nervous System , 1980 .

[149]  J. B. Ranck,et al.  Generation of theta rhythm in medial entorhinal cortex of freely moving rats , 1980, Brain Research.

[150]  A. Gelperin,et al.  Feeding motor programme in Limax. II. Modulation by sensory inputs in intact animals and isolated central nervous systems. , 1980, The Journal of experimental biology.

[151]  R. Gray,et al.  Investigation of burst generation by the electrically coupled cyberchron network in the snail Helisoma using a single-electrode voltage clamp. , 1980, Journal of neurobiology.

[152]  A. Gelperin,et al.  Localization of [3H]-2-deoxy glucose in single molluscan neurones , 1980, Nature.

[153]  M. Burrows The control of sets of motoneurones by local interneurones in the locust. , 1980, The Journal of physiology.

[154]  H. Pinsker,et al.  Neuroethological studies of freely swimming Aplysia brasiliana. , 1980, The Journal of experimental biology.

[155]  M. Burrows,et al.  Non-spiking interneurones and local circuits , 1980, Trends in Neurosciences.

[156]  W. Davis,et al.  Action-potential broadening and endogenously sustained bursting are substrates of command ability in a feeding neuron of Pleurobranchaea. , 1980, Journal of neurophysiology.

[157]  P. Schwindt,et al.  Role of a persistent inward current in motoneuron bursting during spinal seizures. , 1980, Journal of neurophysiology.

[158]  P. R. Lennard,et al.  Central pattern generator mediating swimming in Tritonia. I. Identification and synaptic interactions. , 1980, Journal of neurophysiology.

[159]  Daniel C. Dennett,et al.  Brainstorms: Philosophical Essays on Mind and Psychology , 1981 .

[160]  A. Gelperin,et al.  [3H]2-Deoxyglucose autoradiography in a molluscan nervous system , 1981, Brain Research.

[161]  J. C. Weeks Neuronal basis of leech swimming: separation of swim initiation, pattern generation, and intersegmental coordination by selective lesions. , 1981, Journal of neurophysiology.