Pacemaker neurons and neuronal networks: An integrative view

Current Opinion in Neurobiology

Volumn 14, Issue 6, 2004, Pages 665-674

  Ramirez, Jan Marino ^a   Tryba, Andrew K ^b   Peña, Fernando ^c  

^a UNIVERSITY OF CHICAGO   (United States)

^b TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER   (United States)

^c DEPARTAMENTO DE FÍSICA   (Mexico)

Author keywords

[No Author keywords available]

Indexed keywords

ION CHANNEL;

ADDICTION; AROUSAL; BEHAVIOR; CALCIUM CELL LEVEL; CELL ACTIVITY; COGNITION; CORTICAL SYNCHRONIZATION; ELECTRIC POTENTIAL; EXCITATION; HYPERPOLARIZATION; MEMORY; MOTOR ACTIVITY; NERVE CELL; NERVE CELL NETWORK; NEUROMODULATION; PACEMAKER; PHYSIOLOGY; PRIORITY JOURNAL; REVIEW; RHYTHM; SLEEP; SYNAPTIC POTENTIAL;

ACTION POTENTIALS; ANIMALS; BIOLOGICAL CLOCKS; CENTRAL NERVOUS SYSTEM; HUMANS; ION CHANNELS; MODELS, NEUROLOGICAL; NERVE NET; NEURONS; SYNAPTIC TRANSMISSION;

EID: 9644294519     PISSN: 09594388     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.conb.2004.10.011     Document Type: Review

References (60)

1. Y.I. Arshavsky Cellular and network properties in the functioning of the nervous system: from central pattern generators to cognition Brain Res Brain Res Rev 41 2003 229 267 The author discusses the role of pacemaker activity and network properties in the generation of rhythmic activity. The article shows in an impressive manner that rhythm generation is a fundamental property of the CNS and underlies behavioral functions ranging from motor control to cognition.
2. R.R. Llinas The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function Science 242 1988 1654 1664
3. G. Buzsaki, and A. Draguhn Neuronal oscillations in cortical networks Science 304 2004 1926 1929 "Clocks tick, bridges and skyscrapers vibrate, neuronal network oscillate". This excerpt from the abstract sets the tone for this exciting review on neocortical rhythms that addresses the important question: are neuronal rhythms an inevitable by-product or an essential part of the brain's design? The authors make a convincing case that network rhythms are crucial for many higher brain functions including memory consolidation, temporal representation and input selection. This outstanding review is highly recommended not only for readers who thought that rhythms are only important for generating rhythmic motor activities, but also for those who still suspect that fast oscillations are just an epiphenomenon.
4. P. Schweitzer, S.G. Madamba, and G.R. Siggins The sleep-modulating peptide cortistatin augments the h-current in hippocampal neurons J Neurosci 23 2003 10884 10891
5. h) in ventral tegmental area dopamine neurons: involvement of 5-HT2 receptors and protein kinase C J Neurophysiol 90 2003 3201 3212
6. C.A. Del Negro, C. Morgado-Valle, and J.L. Feldman Respiratory rhythm: an emergent network property? Neuron 34 2002 821 830
7. S.P. Lieske, M. Thoby-Brisson, P. Telgkamp, and J.M. Ramirez Reconfiguration of the neural network controlling multiple breathing patterns: eupnea, sighs and gasps Nat Neurosci 3 2000 600 607
8. J.C. Smith, H.H. Ellenberger, K. Ballanyi, D.W. Richter, and J.L. Feldman Pre-Bötzinger complex: a brainstem region that may generate respiratory rhythm in mammals Science 254 1991 726 729
9. R.M. Harris-Warrick Voltage-sensitive ion channels in rhythmic motor systems Curr Opin Neurobiol 12 2002 646 651
10. A.A. Prinz, C.P. Billimoria, and E. Marder Alternative to hand-tuning conductance-based models: construction and analysis of databases of model neurons J Neurophysiol 90 2003 3998 4015 Whether a neuron is a pacemaker or not is determined by the densities and dynamics of ion channels. Currents flowing through these channels depend in a nonlinear manner on the membrane potential, which itself is changed by the ion fluxes. This very innovative paper introduces a computational approach that will aid our understanding of this complex dynamical interplay and how such interactions lead to a given discharge pattern. The authors create a huge database of model neurons in which the conductances of eight ion channels are varied independently. The database provides extensive information about steady-state voltage traces, spontaneous behaviors and response properties of millions of model neurons. The data can be used to learn how different combinations of ion channels lead to discharge patterns typically found in realistic neurons. It is predicted that this approach will become an invaluable tool in cellular and systems neuroscience.
11. L.B. French, C.C. Lanning, M. Matly, and R.M. Harris-Warrick Cellular localization of Shab and Shaw potassium channels in the lobster stomatogastric ganglion Neuroscience 123 2004 919 930 The discharge pattern of a neuron depends not only on the ion channels, but also on their location. This study is one of several exciting papers published this year by the Harris-Warrick laboratory exploring how different ion channel subtypes are distributed on functionally identified neurons, how these channels interact, and how they are homeostatically regulated in order to generate a functionally identified activity pattern.
12. M.A. Whittington, and R.D. Traub Interneuron diversity series: inhibitory interneurons and network oscillations in vitro Trends Neurosci 26 2003 676 682 In this outstanding review, the authors unravel the interaction between nonlinear membrane properties and synaptic characteristics of different types of hippocampal neuron to understand how these components lead to the differential generation of gamma and theta rhythms. Of importance are the spatial distribution of ion channels and the contribution of electrical synapses. The authors conclude that different types of interneuron have different tasks in generating these rhythms.
13. 2+ signals arriving from different spatial compartments and sources contribute to the discharge pattern of neurons involved in generating rhythmic motor activity.
14. M. Thoby-Brisson, P. Telgkamp, and J.M. Ramirez The role of the hyperpolarization-activated current in modulating rhythmic activity in the isolated respiratory network of mice J Neurosci 20 2000 2994 3005
15. M. Thoby-Brisson, and J.M. Ramirez Two types of inspiratory pacemaker neurons in the isolated respiratory network of mice J Neurophysiol 86 2001 104 112
16. J.C. Rekling, J. Champagnat, and M. Denavit-Saubie Electroresponsive properties and membrane potential trajectories of three types of inspiratory neurons in the newborn mouse brain stem in vitro J Neurophysiol 75 1996 795 810
17. F. Peña, M.A. Parkis, A.K. Tryba, and J.M. Ramirez Differential contribution of pacemaker properties to the generation of respiratory rhythms during normoxia and hypoxia Neuron 43 2004 105 117 This study replaces the prevailing concept that respiratory rhythm is generated by just one neuronal mechanism with the more dynamic concept that heterogeneous and state-dependent mechanisms are important for generating respiratory rhythm. The data suggest that the dependence on pacemaker neurons is not fixed but altered by state-dependent changes, in this case by hypoxia.
18. C.A. Del Negro, N. Koshiya, R.J. Butera Jr., and J.C. Smith Persistent sodium current, membrane properties and bursting behavior of pre-Bötzinger complex inspiratory neurons in vitro J Neurophysiol 88 2002 2242 2250
19. H. Monyer, and H. Markram Interneuron diversity series: molecular and genetic tools to study GABAergic interneuron diversity and function Trends Neurosci 27 2004 90 97 This up-to-date overview describes how modern molecular and genetic tools can be combined with electrophysiological and neuroanatomical approaches to arrive at a better characterization of interneurons and their discharge pattern. The authors discuss novel ways to manipulate interneuronal activity to explore how genes, neurons and networks give rise to complex behaviors.
20. O. Kiehn, and K. Kullander Central pattern generators deciphered by molecular genetics Neuron 41 2004 317 321 The authors review modern molecular and genetic approaches for dissecting the organization and development of rhythm-generating neuronal networks in invertebrate and vertebrate motor systems. These powerful approaches enable a very specific manipulation of neurons that are united by a common genetic or molecular marker, such as the presence of a promoter for a given transcription factor. It is easy to imagine that in the near future many genetic markers will prove useful for differentially manipulating different subpopulations of interneurons, thereby increasing our understanding of how these neurons contribute to the generation of complex network activity.
21. M. Steriade Neocortical cell classes are flexible entities Nat Rev Neurosci 5 2004 121 134 Neocortical neuron types are not fixed but dependent on state. This conclusion is obtained through impressive intracellular recordings from awake and sleeping cats, which indicate that state transitions are associated with a change in the incidence of neuron types and a transformation in discharge patterns: for example, intrinsically bursting neurons can be transformed into regular spiking neurons. This study emphasizes the importance of recording from neurons in a functional and/or behavioral context and shows that a given discharge pattern is not a fixed entity.
22. + conductances.
23. W. Zhang, and D.J. Linden The other side of the engram: experience-driven changes in neuronal intrinsic excitability Nat Rev Neurosci 4 2003 885 900 This important review raises the awareness that neuronal plasticity is restricted not only to changes in synaptic mechanisms, but also to changes in the function of voltage-gated ion channels. Changes in intrinsic excitability might be a powerful mechanism for the consolidation and adaptive generalization of memories.
24. J.N. MacLean, Y. Zhang, B.R. Johnson, and R.M. Harris-Warrick Activity-independent homeostasis in rhythmically active neurons Neuron 37 2003 109 120 With all the known plasticity that can alter the discharge pattern of a neuron, how can neurons maintain a preferred activity range that is functionally meaningful? An elegant series of experiments reveals a novel form of activity-independent regulation of ion channels that could have an essential role in promoting stability in the activity of individual neurons and networks.
25. 2+ interactions are state-dependently regulated and differentially distributed in somatic and dendritic compartments.
26. 2+-regulating mechanisms in form of organelles such as mitochondria.
27. F. Peña, and J.M. Ramirez Endogenous activation of serotonin 2A receptors is required for normal respiratory rhythm generation in vitro J Neurosci 22 2002 11055 11064
28. h current is modulated by distinct pathways of cAMP synthesis that are recruited by synaptic and modulatory mechanisms.
29. B.R. Johnson, P. Kloppenburg, and R.M. Harris-Warrick Dopamine modulation of calcium currents in pyloric neurons of the lobster stomatogastric ganglion J Neurophysiol 90 2003 631 643
30. F.P. Peña, and J.M. Ramirez Substance P mediated modulation of pacemaker properties in the mammalian respiratory network J Neurosci 24 2004 7549 7556
31. A. Ayali, and R.M. Harris-Warrick Monoamine control of the pacemaker kernel and cycle frequency in the lobster pyloric network J Neurosci 19 1999 6712 6722
32. M. van den Top, K. Lee, A.D. Whyment, A.M. Blanks, and D. Spanswick Orexigen-sensitive NPY/AgRP pacemaker neurons in the hypothalamic arcuate nucleus Nat Neurosci 7 2004 493 494 The authors describe a novel class of conditional pacemaker neurons that could play a crucial role in generating the central neuronal response to perturbations in energy balance. The pacemaker properties of these neurons are modulated by substances that are released in response to satiety and hunger.
33. A. Szücs, R.D. Pinto, M.I. Rabinovich, H.D. Abarbanel, and A.I. Selverston Synaptic modulation of the interspike interval signatures of bursting pyloric neurons J Neurophysiol 89 2003 1363 1377 Whether pacemaker bursts are units of neuronal information or whether their internal structure plays an important part in the function of neuronal networks is largely unresolved. In this study, the authors show how synaptic inhibition shapes burst discharges in pacemaker activity. As a result, these neurons express remarkable flexibility, rich dynamical behavior and a plastic input sensitivity in the burst that could be important in regulating network activity.
34. J.C. Smith, R.J. Butera, N. Koshiya, C. Del Negro, C.G. Wilson, and S.M. Johnson Respiratory rhythm generation in neonatal and adult mammals: the hybrid pacemaker-network model Respir Physiol 122 2000 131 147
35. O. Kiehn, O. Kjaerulff, M.C. Tresch, and R.M. Harris-Warrick Contributions of intrinsic motor neuron properties to the production of rhythmic motor output in the mammalian spinal cord Brain Res Bull 53 2000 649 659
36. + channels reduces bursting in FRB neurons and gamma oscillations in the neocortex but not in the hippocampus, suggesting that FRB neurons have a crucial role in the generation of neocortical gamma oscillations.
37. R.J. Butera Jr., J. Rinzel, and J.C. Smith Models of respiratory rhythm generation in the pre-Bötzinger complex. II. Populations of coupled pacemaker neurons J Neurophysiol 82 1999 398 415
38. J.M. Ramirez, P. Telgkamp, F.P. Elsen, U.J. Quellmalz, and D.W. Richter Respiratory rhythm generation in mammals: synaptic and membrane properties Respir Physiol 110 1997 71 85
39. + and imposed changes in the membrane potential. Such a background inward current might be essential for stabilizing rhythm generation not only in the respiratory network but also in other rhythm-generating neuronal networks.
40. N.S. Bamford, H. Zhang, Y. Schmitz, N.P. Wu, C. Cepeda, M.S. Levine, C. Schmauss, S.S. Zakharenko, L. Zablow, and D. Sulzer Heterosynaptic dopamine neurotransmission selects sets of corticostriatal terminals Neuron 42 2004 653 663
41. K.H. Lee, C. Broberger, U. Kim, and D.A. McCormick Histamine modulates thalamocortical activity by activating a chloride conductance in ferret perigeniculate neurons Proc Natl Acad Sci USA 101 2004 6716 6721
42. A. Sakurai, and P.S. Katz Spike timing-dependent serotonergic neuromodulation of synaptic strength intrinsic to a central pattern generator circuit J Neurosci 23 2003 10745 10755
43. W. Van Drongelen, H. Koch, C. Marcuccilli, F. Pena, and J.M. Ramirez Synchrony levels during evoked seizure-like bursts in mouse neocortical slices J Neurophysiol 90 2003 1571 1580
44. H. Onimaru, and I. Homma A novel functional neuron group for respiratory rhythm generation in the ventral medulla J Neurosci 23 2003 1478 1486 Optical recordings show that the respiratory rhythm-generating network extends to a location more rostral than the pre-Bötzinger complex. The authors suggest that pacemaker neurons (the so-called Pre-I neurons) located in the parafacial respiratory group interact with pre-Bötzinger complex neurons in the form of a coupled oscillatory system to regulate respiratory rhythmic activity.
45. N.M. Mellen, W.A. Janczewski, C.M. Bocchiaro, and J.L. Feldman Opioid-induced quantal slowing reveals dual networks for respiratory rhythm generation Neuron 37 2003 821 826 The prevailing concept that a single medullary network generates respiratory rhythmic activity is proved to be wrong in this important study. In a very convincing series of experiments, the authors show that two rhythmically active networks interact to generate respiratory rhythmic activity, and that under different conditions each is sufficient to generate a respiratory rhythm. Both networks have different modulatory sensitivities. The authors discuss the possibility that the differential sensitivities might enhance the robustness of the respiratory rhythm.
46. H. Onimaru, A. Arata, and I. Homma Intrinsic burst generation of preinspiratory neurons in the medulla of brainstem-spinal cord preparations isolated from newborn rats Exp Brain Res 106 1995 57 68
47. C.F. Poets Apparent life-threatening events and sudden infant death on a monitor Paediatr Respir Rev 5 Suppl A 2004 S383 S386
48. R. Sridhar, B.T. Thach, D.H. Kelly, and J.A. Henslee Characterization of successful and failed autoresuscitation in human infants, including those dying of SIDS Pediatr Pulmonol 36 2003 113 122
49. H.C. Kinney, L.L. Randall, L.A. Sleeper, M. Willinger, R.A. Belliveau, N. Zec, L.A. Rava, L. Dominici, S. Iyasu, and B. Randall Serotonergic brainstem abnormalities in Northern Plains Indians with the sudden infant death syndrome J Neuropathol Exp Neurol 62 2003 1178 1191
50. N.C. Dembrow, J. Jing, V. Brezina, and K.R. Weiss A specific synaptic pathway activates a conditional plateau potential underlying protraction phase in the Aplysia feeding central pattern generator J Neurosci 24 2004 5230 5238
51. M. Brecht, M. Schneider, B. Sakmann, and T.W. Margrie Whisker movements evoked by stimulation of single pyramidal cells in rat motor cortex Nature 427 2004 704 710 Those readers who think that single neurons do not matter in the mammalian nervous system are proved wrong in this exciting study. Stimulation of a single pyramidal neuron is able to reset and to initiate rhythmic whisker movements. The authors propose that sparse cortical activity in the vibrissae motor cortex is sufficient to generate motor output by disynaptically activating a central pattern generator in the facial nucleus.
52. G. Buzsaki Large-scale recording of neuronal ensembles Nat Neurosci 7 2004 446 451
53. P. Bartho, H. Hirase, L. Monconduit, M. Zugaro, K.D. Harris, and G. Buzsaki Characterization of neocortical principal cells and interneurons by network interactions and extracellular features J Neurophysiol 92 2004 600 608
54. A.M. Thomson Presynaptic frequency- and pattern-dependent filtering J Comput Neurosci 15 2003 159 202
55. Y. Shu, A. Hasenstaub, and D.A. McCormick Turning on and off recurrent balanced cortical activity Nature 423 2003 288 293 By using isolated neocortical slices that spontaneously generate up-and-down states, this study demonstrates that local cortical circuits operate through a balance of synaptic excitation and inhibition generated through local recurrent connections. The authors' finding is consistent with the hypothesis that recurrent activity is a basic operational principle of the cerebral cortex.
56. K.T. Blackwell, U. Czubayko, and D. Plenz Quantitative estimate of synaptic inputs to striatal neurons during up and down states in vitro J Neurosci 23 2003 9123 9132
57. T. Klausberger, P.J. Magill, L.F. Marton, J.D. Roberts, P.M. Cobden, G. Buzsaki, and P. Somogyi Brain-state- and cell-type-specific firing of hippocampal interneurons in vivo Nature 421 2003 844 848 Hippocampal network oscillations occurring at distinct frequencies have been implicated in the encoding, consolidation and retrieval of information. This study shows that three types of interneuron contribute differentially to different aspects of theta and ripple oscillations. The authors propose that the large diversity of GABAergic interneurons evolved to control pyramidal cells in a temporally distinct and brain-state dependent manner.
58. S.J. Butt, and O. Kiehn Functional identification of interneurons responsible for left-right coordination of hindlimbs in mammals Neuron 38 2003 953 963 The authors identify a class of interneurons that are crucial for the generation of locomotor activity. Interestingly, some of the connections described in this study are reconfigured on switching from rest to locomotion via a mechanism that might be associated with synaptic plasticity in the spinal cord.
59. A.L. Weaver, and S.L. Hooper Relating network synaptic connectivity and network activity in the lobster (Panulirus interruptus) pyloric network J Neurophysiol 90 2003 2378 2386 How do the activity of single pacemaker neurons and their synaptic interactions contribute to the generation of a network output? This important issue is addressed in the stomatogastric ganglion of crustacean, perhaps the best-understood motor network. Surprisingly, the authors find that despite producing very similar rhythmic output, networks from different individuals have varied cellular and synaptic properties. Removal of single neurons often has little effect on the activity of its postsynaptic partners and is inconsistent across preparations.
60. C.C. Horn, Y. Zhurov, I.V. Orekhova, A. Proekt, I. Kupfermann, K.R. Weiss, and V. Brezina Cycle-to-cycle variability of neuromuscular activity in Aplysia feeding behavior J Neurophysiol 92 2004 157 180 This intriguing paper investigates cycle-to-cycle variability in the feeding behavior of the sea slug Aplysia recorded in reduced preparations and intact animals. The study demonstrates that variability has real existence at all levels of this rhythmic behavior. The authors propose that variability is a part of an optimal strategy of trial, error and stabilization that the CNS adopts in an uncertain environment. This built-in variability is often overlooked because most studies focus on the average value; however, cycle-to-cycle variability might have important functional significance for the operation of central pattern generators in general.