Variability, compensation and homeostasis in neuron and network function (original) (raw)

• Hanwell, D., Ishikawa, T., Saleki, R. & Rotin, D. Trafficking and cell surface stability of the epithelial Na+ channel expressed in epithelial Madin–Darby canine kidney cells. J. Biol. Chem. 277, 9772–9779 (2002).
  Article CAS PubMed Google Scholar
• Monjaraz, E. et al. L-type calcium channel activity regulates sodium channel levels in rat pituitary GH3 cells. J. Physiol. (Lond.) 523, 45–55 (2000).
  Article CAS Google Scholar
• Jugloff, D. G., Khanna, R., Schlichter, L. C. & Jones, O. T. Internalization of the Kv1.4 potassium channel is suppressed by clustering interactions with PSD-95. J. Biol. Chem. 275, 1357–1364 (2000).
  Article CAS PubMed Google Scholar
• Staub, O. et al. Regulation of stability and function of the epithelial Na+ channel (ENaC) by ubiquitination. EMBO J. 16, 6325–6336 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Bruneau, E. G., Macpherson, P. C., Goldman, D., Hume, R. I. & Akaaboune, M. The effect of agrin and laminin on acetylcholine receptor dynamics in vitro. Dev. Biol. 288, 248–258 (2005).
  Article CAS PubMed Google Scholar
• LeMasson, G., Marder, E. & Abbott, L. F. Activity-dependent regulation of conductances in model neurons. Science 259, 1915–1917 (1993). This theoretical paper was the first attempt to suggest that neuronal excitability might be controlled by a negative feedback, homeostatic mechanism in which the neuron's target activity is maintained despite channel turnover.
  Article CAS PubMed Google Scholar
• Liu, Z., Golowasch, J., Marder, E. & Abbott, L. F. A model neuron with activity-dependent conductances regulated by multiple calcium sensors. J. Neurosci. 18, 2309–2320 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Marder, E. & Prinz, A. A. Modeling stability in neuron and network function: the role of activity in homeostasis. Bioessays 24, 1145–1154 (2002).
  Article CAS PubMed Google Scholar
• Turrigiano, G. G. & Nelson, S. B. Homeostatic plasticity in the developing nervous system. Nature Rev. Neurosci. 5, 97–107 (2004). An outstanding review article that discusses homeostatic regulation of synaptic strength and intrinsic excitability.
  Article CAS Google Scholar
• Davis, G. W. Homeostatic control of neural activity: from phenomenology to molecular design. Annu. Rev. Neurosci. 20 Mar 2006 (doi:10.1146/annurev.neuro.28.061604.135751). This review article provides a discussion of the outstanding questions relevant to homeostatic regulation. In particular, it addresses what is known about how targets for homeostatic regulation might be set.
• Turrigiano, G. G., Leslie, K. R., Desai, N. S., Rutherford, L. C. & Nelson, S. B. Activity-dependent scaling of quantal amplitude in neocortical neurons. Nature 391, 892–896 (1998). This now classic paper provided the first direct demonstration that a neuron slowly regulates the strength of all of its synapses in a multiplicative fashion.
  Article CAS PubMed Google Scholar
• Turrigiano, G. G. & Nelson, S. B. Hebb and homeostasis in neuronal plasticity. Curr. Opin. Neurobiol. 10, 358–364 (2000).
  Article CAS PubMed Google Scholar
• Desai, N. S., Rutherford, L. C. & Turrigiano, G. G. Plasticity in the intrinsic excitability of cortical pyramidal neurons. Nature Neurosci. 2, 515–520 (1999). Provides a direct demonstration of changes in current densities as a response to activity deprivation. Working with cultured cortical neurons, the authors show upregulation of Na+ currents and downregulation of K+ currents in response to 48 h of TTX treatment.
  Article CAS PubMed Google Scholar
• Zhang, W. & Linden, D. J. The other side of the engram: experience-driven changes in neuronal intrinsic excitability. Nature Rev. Neurosci. 4, 885–900 (2003).
  Article CAS Google Scholar
• Aizenman, C. D., Akerman, C. J., Jensen, K. R. & Cline, H. T. Visually driven regulation of intrinsic neuronal excitability improves stimulus detection in vivo. Neuron 39, 831–842 (2003).
  Article CAS PubMed Google Scholar
• Hille, B. Ion Channels of Excitable Membranes (Sinauer, Sunderland, Massachusetts, 2001).
  Google Scholar
• Connor, J. A. & Stevens, C. F. Prediction of repetitive firing behaviour from voltage clamp data on an isolated neurone soma. J. Physiol. (Lond.) 213, 31–53 (1971).
  Article CAS Google Scholar
• Connor, J. A. & Stevens, C. F. Voltage clamp studies of a transient outward membrane current in gastropod neural somata. J. Physiol. (Lond.) 213, 21–30 (1971).
  Article CAS Google Scholar
• Meech, R. W. Calcium-dependent potassium activation in nervous tissues. Annu. Rev. Biophys. Bioeng. 7, 1–18 (1978).
  Article CAS PubMed Google Scholar
• Connor, J. A., Walter, D. & McKown, R. Neural repetitive firing: modifications of the Hodgkin–Huxley axon suggested by experimental results from crustacean axons. Biophys. J. 18, 81–102 (1977).
  Article CAS PubMed PubMed Central Google Scholar
• Sah, P. & Faber, E. S. Channels underlying neuronal calcium-activated potassium currents. Prog. Neurobiol. 66, 345–353 (2002).
  Article CAS PubMed Google Scholar
• Pennefather, P., Lancaster, B., Adams, P. R. & Nicoll, R. A. Two distinct Ca-dependent K currents in bullfrog sympathetic ganglion cells. Proc. Natl Acad. Sci. USA 82, 3040–3044 (1985).
  Article CAS PubMed PubMed Central Google Scholar
• Day, M. et al. Dendritic excitability of mouse frontal cortex pyramidal neurons is shaped by the interaction among HCN, Kir2, and Kleak channels. J. Neurosci. 25, 8776–8787 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Ma, M. & Koester, J. The role of potassium currents in frequency-dependent spike broadening in Aplysia R20 neurons: a dynamic clamp analysis. J. Neurosci. 16, 4089–4101 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Swensen, A. M. & Bean, B. P. Ionic mechanisms of burst firing in dissociated Purkinje neurons. J. Neurosci. 23, 9650–63 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Chen, K. et al. Persistently modified h-channels after complex febrile seizures convert the seizure-induced enhancement of inhibition to hyperexcitability. Nature Med. 7, 331–337 (2001). In contrast to most studies that depend on pharmacological manipulations to demonstrate homeostatic regulation, here the authors exploit a disease paradigm, febrile seizures, to study the interaction between synaptic and intrinsic excitability.
  Article CAS PubMed Google Scholar
• French, C. R., Sah, P., Buckett, K. J. & Gage, P. W. A voltage-dependent persistent sodium current in mammalian hippocampal neurons. J. Gen. Physiol. 95, 1139–1157 (1990).
  Article CAS PubMed Google Scholar
• Hoffman, D. A., Magee, J. C., Colbert, C. M. & Johnston, D. K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons. Nature 387, 869–875 (1997).
  Article CAS PubMed Google Scholar
• Fraser, D. D. & MacVicar, B. A. Low-threshold transient calcium current in rat hippocampal lacunosum-moleculare interneurons: kinetics and modulation by neurotransmitters. J. Neurosci. 11, 2812–2820 (1991).
  Article CAS PubMed PubMed Central Google Scholar
• Ngo-Anh, T. J. et al. SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines. Nature Neurosci. 8, 642–649 (2005).
  Article CAS PubMed Google Scholar
• Vervaeke, K., Hu, H., Graham, L. J. & Storm, J. F. Contrasting effects of the persistent Na+ current on neuronal excitability and spike timing. Neuron 49, 257–270 (2006).
  Article CAS PubMed Google Scholar
• Magee, J. C. Dendritic hyperpolarization-activated currents modify the integrative properties of hippocampal CA1 pyramidal neurons. J. Neurosci. 18, 7613–7624 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Ramakers, G. M. & Storm, J. F. A postsynaptic transient K+ current modulated by arachidonic acid regulates synaptic integration and threshold for LTP induction in hippocampal pyramidal cells. Proc. Natl Acad. Sci. USA 99, 10144–10149 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Gillessen, T. & Alzheimer, C. Amplification of EPSPs by low Ni2+- and amiloride-sensitive Ca2+ channels in apical dendrites of rat CA1 pyramidal neurons. J. Neurophysiol. 77, 1639–1643 (1997).
  Article CAS PubMed Google Scholar
• Wolfart, J., Debay, D., Le Masson, G., Destexhe, A. & Bal, T. Synaptic background activity controls spike transfer from thalamus to cortex. Nature Neurosci. 8, 1760–1767 (2005).
  Article CAS PubMed Google Scholar
• Pape, H. C. & McCormick, D. A. Noradrenaline and serotonin selectively modulate thalamic burst firing by enhancing a hyperpolarization-activated cation current. Nature 340, 715–718 (1989).
  Article CAS PubMed Google Scholar
• Luthi, A. & McCormick, D. A. H-current: properties of a neuronal and network pacemaker. Neuron 21, 9–12 (1998).
  Article CAS PubMed Google Scholar
• Golowasch, J., Goldman, M. S., Abbott, L. F. & Marder, E. Failure of averaging in the construction of a conductance-based neuron model. J. Neurophysiol. 87, 1129–1131 (2002).
  Article PubMed Google Scholar
• Foster, W. R., Ungar, L. H. & Schwaber, J. S. Significance of conductances in Hodgkin–Huxley models. J. Neurophysiol. 70, 2502–2518 (1993).
  Article CAS PubMed Google Scholar
• Taylor, A. L., Hickey, T. J., Prinz, A. A. & Marder, E. Structure and visualization of high-dimensional conductance spaces. J. Neurophysiol. (in the press).
• Goldman, M. S., Golowasch, J., Marder, E. & Abbott, L. F. Global structure, robustness, and modulation of neuronal models. J. Neurosci. 21, 5229–5238 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Schulz, D. J., Goaillard, J. M. & Marder, E. Variable channel expression in identified single and electrically coupled neurons in different animals. Nature Neurosci. 9, 356–362 (2006). Combines voltage clamp analyses and real-time PCR measurements of mRNA copy number in single neurons, and finds that both measures vary considerably in the single LP neuron from different animals. Although pyloric dilator neurons also show considerable animal-to-animal variability, the two electrically coupled neurons from the same animal show very similar levels of channel mRNA expression.
  Article CAS PubMed Google Scholar
• Swensen, A. M. & Bean, B. P. Robustness of burst firing in dissociated purkinje neurons with acute or long-term reductions in sodium conductance. J. Neurosci. 25, 3509–3520 (2005). A fascinating study that raises many important issues. Among them is the observation that individual cerebellar Purkinje neurons that show almost identical patterns of electrical activity have quite different ratios of inward Na+ and Ca 2+ currents.
  Article CAS PubMed PubMed Central Google Scholar
• Baro, D. J. et al. Quantitative single-cell-reverse transcription-PCR demonstrates that A- current magnitude varies as a linear function of shal gene expression in identified stomatogastric neurons. J. Neurosci. 17, 6597–6610 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Golowasch, J., Abbott, L. F. & Marder, E. Activity-dependent regulation of potassium currents in an identified neuron of the stomatogastric ganglion of the crab Cancer borealis. J. Neurosci. 19, RC33 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Liss, B. et al. Tuning pacemaker frequency of individual dopaminergic neurons by Kv4.3L and KChip3.1 transcription. EMBO J. 20, 5715–24 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Harris-Warrick, R. M. & Flamm, R. E. Multiple mechanisms of bursting in a conditional bursting neuron. J. Neurosci. 7, 2113–2128 (1987).
  Article CAS PubMed PubMed Central Google Scholar
• Harris-Warrick, R. M., Coniglio, L. M., Barazangi, N., Guckenheimer, J. & Gueron, S. Dopamine modulation of transient potassium current evokes phase shifts in a central pattern generator network. J. Neurosci. 15, 342–358 (1995).
  Article CAS PubMed PubMed Central Google Scholar
• Guckenheimer, J., Gueron, S. & Harris-Warrick, R. M. Mapping the dynamics of a bursting neuron. Phil. Trans. R. Soc. Lond. B 341, 345–359 (1993).
  Article CAS Google Scholar
• Guckenheimer, J., Harris-Warrick, R., Peck, J. & Willms, A. Bifurcation, bursting, and spike frequency adaptation. J. Comput. Neurosci. 4, 257–277 (1997).
  Article CAS PubMed Google Scholar
• Prinz, A. A., Thirumalai, V. & Marder, E. The functional consequences of changes in the strength and duration of synaptic inputs to oscillatory neurons. J. Neurosci. 23, 943–954 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Piedras-Renteria, E. S. et al. Presynaptic homeostasis at CNS nerve terminals compensates for lack of a key Ca2+ entry pathway. Proc. Natl Acad. Sci. USA 101, 3609–3614 (2004). Remarkably, genetic knockouts of the P/Q type Ca 2+ channel have relatively little effect on synaptic transmission, because of compensation by other mechanisms.
  Article CAS PubMed PubMed Central Google Scholar
• Thiagarajan, T. C., Lindskog, M. & Tsien, R. W. Adaptation to synaptic inactivity in hippocampal neurons. Neuron 47, 725–737 (2005).
  Article CAS PubMed Google Scholar
• Vahasoyrinki, M., Niven, J., Hardie, R., Weckstrom, M. & Juusola, M. Robustness of neural coding in Drosophila photoreceptors in the absence of slow delayed rectifier K+ channels. J. Neurosci. 26, 2652–2660 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• MacLean, J. N., Zhang, Y., Johnson, B. R. & Harris-Warrick, R. M. Activity-independent homeostasis in rhythmically active neurons. Neuron 37, 109–120 (2003). In this paper, the authors inject mRNA for shal, resulting in large (three- to fourfold) increases in I A without changes in firing, because the upregulation in I A is accompanied by compensatory changes in I H . Because short-term manipulations of I A result in changes in activity, this paper directly illustrates the difference between short-term pharmacological manipulation of a current and long-term changes that are accompanied by compensation.
  Article CAS PubMed Google Scholar
• MacLean, J. N. et al. Activity-independent coregulation of _I_A and _I_h in rhythmically active neurons. J. Neurophysiol. 94, 3601–3617 (2005).
  Article PubMed Google Scholar
• Tierney, A. J. & Harris-Warrick, R. M. Physiological role of the transient potassium current in the pyloric circuit of the lobster stomatogastric ganglion. J. Neurophysiol. 67, 599–609 (1992).
  Article CAS PubMed Google Scholar
• Zhang, Y. et al. Overexpression of a hyperpolarization-activated cation current (_I_h) channel gene modifies the firing activity of identified motor neurons in a small neural network. J. Neurosci. 23, 9059–9067 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Nusbaum, M. P. & Marder, E. A modulatory proctolin-containing neuron (MPN). II. State-dependent modulation of rhythmic motor activity. J. Neurosci. 9, 1600–1607 (1989).
  Article CAS PubMed PubMed Central Google Scholar
• Kiehn, O. & Harris-Warrick, R. M. 5-HT modulation of hyperpolarization-activated inward current and calcium-dependent outward current in a crustacean motor neuron. J. Neurophysiol. 68, 496–508 (1992).
  Article CAS PubMed Google Scholar
• Harris-Warrick, R. M. et al. Distributed effects of dopamine modulation in the crustacean pyloric network. Ann. NY Acad. Sci. 860, 155–167 (1998).
  Article CAS PubMed Google Scholar
• Elson, R. C. & Selverston, A. I. Mechanisms of gastric rhythm generation in isolated stomatogastric ganglion of spiny lobsters: bursting pacemaker potentials, synaptic interactions and muscarinic modulation. J. Neurophysiol. 68, 890–907 (1992).
  Article CAS PubMed Google Scholar
• Szucs, A., Abarbanel, H. D., Rabinovich, M. I. & Selverston, A. I. Dopamine modulation of spike dynamics in bursting neurons. Eur. J. Neurosci. 21, 763–772 (2005).
  Article PubMed Google Scholar
• Turrigiano, G., Abbott, L. F. & Marder, E. Activity-dependent changes in the intrinsic properties of cultured neurons. Science 264, 974–977 (1994).
  Article CAS PubMed Google Scholar
• Siegel, M., Marder, E. & Abbott, L. F. Activity-dependent current distributions in model neurons. Proc. Natl Acad. Sci. USA 91, 11308–11312 (1994).
  Article CAS PubMed PubMed Central Google Scholar
• Stemmler, M. & Koch, C. How voltage-dependent conductances can adapt to maximize the information encoded by neuronal firing rate. Nature Neurosci. 2, 521–527 (1999).
  Article CAS PubMed Google Scholar
• Bito, H., Deisseroth, K. & Tsien, R. W. CREB phosphorylation and dephosphorylation: a Ca2+-and stimulus duration-dependent switch for hippocampal gene expression. Cell 87, 1203–1214 (1996).
  Article CAS PubMed Google Scholar
• Deisseroth, K., Mermelstein, P. G., Xia, H. & Tsien, R. W. Signaling from synapse to nucleus: the logic behind the mechanisms. Curr. Opin. Neurobiol. 13, 354–365 (2003).
  Article CAS PubMed Google Scholar
• Deisseroth, K. & Tsien, R. W. Dynamic multiphosphorylation passwords for activity-dependent gene expression. Neuron 34, 179–182 (2002).
  Article CAS PubMed Google Scholar
• Morozov, A. et al. Rap1 couples cAMP signaling to a distinct pool of p42/44MAPK regulating excitability, synaptic plasticity, learning, and memory. Neuron 39, 309–325 (2003).
  Article CAS PubMed Google Scholar
• Pittenger, C. & Kandel, E. R. In search of general mechanisms for long-lasting plasticity: Aplysia and the hippocampus. Phil. Trans. R. Soc. Lond. B 358, 757–763 (2003).
  Article Google Scholar
• Schorge, S., Gupta, S., Lin, Z., McEnery, M. W. & Lipscombe, D. Calcium channel activation stabilizes a neuronal calcium channel mRNA. Nature Neurosci. 2, 785–790 (1999).
  Article CAS PubMed Google Scholar
• Sugino, K. et al. Molecular taxonomy of major neuronal classes in the adult mouse forebrain. Nature Neurosci. 9, 99–107 (2006). The authors use microarrays to classify populations of neurons in the mouse forebrain as part of an attempt to determine how many different types of neuronal class exist in major brain neurons.
  Article CAS PubMed Google Scholar
• Kamme, F. et al. Single-cell microarray analysis in hippocampus CA1: demonstration and validation of cellular heterogeneity. J. Neurosci. 23, 3607–3615 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Tietjen, I., Rihel, J. & Dulac, C. G. Single-cell transcriptional profiles and spatial patterning of the mammalian olfactory epithelium. Int. J. Dev. Biol. 49, 201–207 (2005).
  Article CAS PubMed Google Scholar
• Tanaka, H. et al. Proteasomal degradation of Kir6.2 channel protein and its inhibition by a Na+ channel blocker aprindine. Biochem. Biophys. Res. Commun. 331, 1001–1006 (2005).
  Article CAS PubMed Google Scholar
• Prinz, A. A., Billimoria, C. P. & Marder, E. Alternative to hand-tuning conductance-based models: construction and analysis of databases of model neurons. J. Neurophysiol. 90, 3998–4015 (2003).
  Article PubMed Google Scholar
• Prinz, A. A., Bucher, D. & Marder, E. Similar network activity from disparate circuit parameters. Nature Neurosci. 7, 1345–1352 (2004). The authors constructed >20 million model networks, then characterized their behaviour. The salient result of this study is that very similar output patterns can result from dramatically different sets of underlying parameters.
  Article CAS PubMed Google Scholar
• Davis, G. W. & Bezprozvanny, I. Maintaining the stability of neural function: a homeostatic hypothesis. Annu. Rev. Physiol. 63, 847–869 (2001).
  Article CAS PubMed Google Scholar
• Turrigiano, G. G. & Nelson, S. B. Thinking globally, acting locally: AMPA receptor turnover and synaptic strength. Neuron 21, 933–935 (1998).
  Article CAS PubMed Google Scholar
• Soto-Trevino, C., Thoroughman, K. A., Marder, E. & Abbott, L. F. Activity-dependent modification of inhibitory synapses in models of rhythmic neural networks. Nature Neurosci. 4, 297–303 (2001).
  Article CAS PubMed Google Scholar
• Paradis, S., Sweeney, S. T. & Davis, G. W. Homeostatic control of presynaptic release is triggered by postsynaptic membrane depolarization. Neuron 30, 737–749 (2001).
  Article CAS PubMed Google Scholar
• Mody, I. Aspects of the homeostaic plasticity of GABAA receptor-mediated inhibition. J. Physiol. (Lond.) 562, 37–46 (2005).
  Article CAS Google Scholar
• Rutherford, L. C., DeWan, A., Lauer, H. M. & Turrigiano, G. G. Brain-derived neurotrophic factor mediates the activity-dependent regulation of inhibition in neocortical cultures. J. Neurosci. 17, 4527–4535 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Kilman, V., van Rossum, M. C. & Turrigiano, G. G. Activity deprivation reduces miniature IPSC amplitude by decreasing the number of postsynaptic GABAA receptors clustered at neocortical synapses. J. Neurosci. 22, 1328–1337 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Erickson, J. D., De Gois, S., Varoqui, H., Schafer, M. K. & Weihe, E. Activity-dependent regulation of vesicular glutamate and GABA transporters: a means to scale quantal size. Neurochem. Int. 48, 643–649 (2006).
  Article CAS PubMed Google Scholar
• Swanwick, C. C., Murthy, N. R. & Kapur, J. Activity-dependent scaling of GABAergic synapse strength is regulated by brain-derived neurotrophic factor. Mol. Cell. Neurosci. 31, 481–492 (2006).
  Article CAS PubMed Google Scholar
• De Gois, S. et al. Homeostatic scaling of vesicular glutamate and GABA transporter expression in rat neocortical circuits. J. Neurosci. 25, 7121–7133 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Bucher, D., Prinz, A. A. & Marder, E. Animal-to-animal variability in motor pattern production in adults and during growth. J. Neurosci. 25, 1611–1619 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Manor, Y., Nadim, F., Abbott, L. F. & Marder, E. Temporal dynamics of graded synaptic transmission in the lobster stomatogastric ganglion. J. Neurosci. 17, 5610–5621 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Thirumalai, V., Prinz, A. A., Johnson, C. D. & Marder, E. Red pigment concentrating hormone strongly enhances the strength of the feedback to the pyloric rhythm oscillator but has little effect on pyloric rhythm period. J. Neurophysiol. 95, 1762–1770 (2006).
  Article CAS PubMed Google Scholar
• Tobin, A. E. & Calabrese, R. L. Myomodulin increases _I_h and inhibits the NA/K pump to modulate bursting in leech heart interneurons. J. Neurophysiol. 94, 3938–3950 (2005).
  Article CAS PubMed Google Scholar
• Rabbah, P. & Nadim, F. Synaptic dynamics do not determine proper phase of activity in a central pattern generator. J. Neurosci. 25, 11269–11278 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Eisen, J. S. & Marder, E. A mechanism for production of phase shifts in a pattern generator. J. Neurophysiol. 51, 1375–1393 (1984).
  Article CAS PubMed Google Scholar
• Olsen, Ø. H. & Calabrese, R. L. Activation of intrinsic and synaptic currents in leech heart interneurons by realistic waveforms. J. Neurosci. 16, 4958–4970 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Sorensen, M., DeWeerth, S., Cymbalyuk, G. & Calabrese, R. L. Using a hybrid neural system to reveal regulation of neuronal network activity by an intrinsic current. J. Neurosci. 24, 5427–5438 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Hartline, D. K., Russell, D. F., Raper, J. A. & Graubard, K. Special cellular and synaptic mechanisms in motor pattern generation. Comp. Biochem. Physiol. 91C, 115–131 (1988).
  Google Scholar
• Goulding, M. & Pfaff, S. L. Development of circuits that generate simple rhythmic behaviors in vertebrates. Curr. Opin. Neurobiol. 15, 14–20 (2005).
  Article CAS PubMed Google Scholar
• Turrigiano, G. G., Marder, E. & Abbott, L. F. Cellular short-term memory from a slow potassium conductance. J. Neurophysiol. 75, 963–966 (1996).
  Article CAS PubMed Google Scholar
• Santhakumar, V. & Soltesz, I. Plasticity of interneuronal species diversity and parameter variance in neurological diseases. Trends Neurosci. 27, 504–510 (2004).
  Article CAS PubMed Google Scholar
• Aradi, I. & Soltesz, I. Modulation of network behaviour by changes in variance in interneuronal properties. J. Physiol. (Lond.) 538, 227–251 (2002).
  Article CAS Google Scholar
• Aradi, I., Santhakumar, V., Chen, K. & Soltesz, I. Postsynaptic effects of GABAergic synaptic diversity: regulation of neuronal excitability by changes in IPSC variance. Neuropharmacology 43, 511–522 (2002).
  Article CAS PubMed Google Scholar
• Aradi, I., Santhakumar, V. & Soltesz, I. Impact of heterogeneous perisomatic IPSC populations on pyramidal cell firing rates. J. Neurophysiol. 91, 2849–2858 (2004).
  Article PubMed Google Scholar
• Foldy, C., Aradi, I., Howard, A. & Soltesz, I. Diversity beyond variance: modulation of firing rates and network coherence by GABAergic subpopulations. Eur. J. Neurosci. 19, 119–130 (2004).
  Article PubMed Google Scholar
• Monier, C., Chavane, F., Baudot, P., Graham, L. J. & Fregnac, Y. Orientation and direction selectivity of synaptic inputs in visual cortical neurons: a diversity of combinations produces spike tuning. Neuron 37, 663–680 (2003).
  Article CAS PubMed Google Scholar
• Marino, J. et al. Invariant computations in local cortical networks with balanced excitation and inhibition. Nature Neurosci. 8, 194–201 (2005).
  Article CAS PubMed Google Scholar
• Schummers, J., Marino, J. & Sur, M. Synaptic integration by V1 neurons depends on location within the orientation map. Neuron 36, 969–978 (2002).
  Article CAS PubMed Google Scholar
• Chiba, A., Kamper, G. & Murphey, R. K. Response properties of interneurons of the cricket cercal sensory system are conserved in spite of changes in peripheral receptors during maturation. J. Exp. Biol. 164, 205–226 (1992).
  Article Google Scholar
• Pulver, S. R., Bucher, D., Simon, D. J. & Marder, E. Constant amplitude of postsynaptic responses for single presynaptic action potentials but not bursting input during growth of an identified neuromuscular junction in the lobster, Homarus americanus. J. Neurobiol. 62, 47–61 (2005).
  Article PubMed Google Scholar
• Hill, A. A., Edwards, D. H. & Murphey, R. K. The effect of neuronal growth on synaptic integration. J. Comput. Neurosci. 1, 239–254 (1994).
  Article CAS PubMed Google Scholar
• Olsen, O., Nadim, F., Hill, A. A. & Edwards, D. H. Uniform growth and neuronal integration. J. Neurophysiol. 76, 1850–1857 (1996).
  Article CAS PubMed Google Scholar
• Hochner, B. & Spira, M. E. Preservation of motoneuron electrotonic characteristics during postembryonic growth. J. Neurosci. 7, 261–270 (1987).
  Article CAS PubMed PubMed Central Google Scholar
• Golowasch, J., Casey, M., Abbott, L. F. & Marder, E. Network stability from activity-dependent regulation of neuronal conductances. Neural Comput. 11, 1079–1096 (1999).
  Article CAS PubMed Google Scholar
• Luther, J. A. et al. Episodic bouts of activity accompany recovery of rhythmic output by a neuromodulator- and activity-deprived adult neural network. J. Neurophysiol. 90, 2720–2730 (2003).
  Article PubMed Google Scholar
• Mizrahi, A. et al. Long-term maintenance of channel distribution in a central pattern generator neuron by neuromodulatory inputs revealed by decentralization in organ culture. J. Neurosci. 21, 7331–7339 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Thoby-Brisson, M. & Simmers, J. Neuromodulatory inputs maintain expression of a lobster motor pattern-generating network in a modulation-dependent state: evidence from long-term decentralization in vitro. J. Neurosci. 18, 2212–2225 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Thoby-Brisson, M. & Simmers, J. Transition to endogenous bursting after long-term decentralization requires de novo transcription in a critical time window. J. Neurophysiol. 84, 596–599 (2000).
  Article CAS PubMed Google Scholar
• Thoby-Brisson, M. & Simmers, J. Long-term neuromodulatory regulation of a motor pattern-generating network: maintenance of synaptic efficacy and oscillatory properties. J. Neurophysiol. 88, 2942–2953 (2002).
  Article PubMed Google Scholar
• Bekoff, A. Spontaneous embryonic motility: an enduring legacy. Int. J. Dev. Neurosci. 19, 155–160 (2001).
  Article CAS PubMed Google Scholar
• Ben-Ari, Y. Developing networks play a similar melody. Trends Neurosci. 24, 353–360 (2001).
  Article CAS PubMed Google Scholar
• Feller, M. B. Spontaneous correlated activity in developing neural circuits. Neuron 22, 653–656 (1999).
  Article CAS PubMed Google Scholar
• O'Donovan, M. J. The origin of spontaneous activity in developing networks of the vertebrate nervous system. Curr. Opin. Neurobiol. 9, 94–104 (1999).
  Article CAS PubMed Google Scholar
• Marder, E. & Rehm, K. J. Development of central pattern generating circuits. Curr. Opin. Neurobiol. 15, 86–93 (2005).
  Article CAS PubMed Google Scholar
• Fénelon, V. S., Casasnovas, B., Simmers, J. & Meyrand, P. Development of rhythmic pattern generators. Curr. Opin. Neurobiol. 8, 705–709 (1998).
  Article PubMed Google Scholar
• O'Donovan, M. J., Bonnot, A., Wenner, P. & Mentis, G. Z. Calcium imaging of network function in the developing spinal cord. Cell Calcium 37, 443–450 (2005).
  Article CAS PubMed Google Scholar
• Wenner, P. & O'Donovan, M. J. Mechanisms that initiate spontaneous network activity in the developing chick spinal cord. J. Neurophysiol. 86, 1481–1498 (2001).
  Article CAS PubMed Google Scholar
• Gonzalez-Islas, C. & Wenner, P. Spontaneous network activity in the embryonic spinal cord regulates AMPAergic and GABAergic synaptic strength. Neuron 49, 563–575 (2006).
  Article CAS PubMed Google Scholar
• Greenspan, R. J. The flexible genome. Nature Rev. Genet. 2, 383–387 (2001). An important philosophical discussion of what we can expect from attempting a genetic analysis of behaviour, given the complex interrelationships of biochemical and molecular signalling networks.
  Article CAS PubMed Google Scholar
• Greenspan, R. J. E pluribus unum, ex uno plura: quantitative and single-gene perspectives on the study of behavior. Annu. Rev. Neurosci. 27, 79–105 (2004).
  Article CAS PubMed Google Scholar
• Alon, U., Surette, M. G., Barkai, N. & Leibler, S. Robustness in bacterial chemotaxis. Nature 397, 168–171 (1999).
  Article CAS PubMed Google Scholar
• Barkai, N. & Leibler, S. Robustness in simple biochemical networks. Nature 387, 913–917 (1997).
  Article CAS PubMed Google Scholar
• Ma'ayan, A., Blitzer, R. D. & Iyengar, R. Toward predictive models of mammalian cells. Annu. Rev. Biophys. Biomol. Struct. 34, 319–349 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Meir, E., von Dassow, G., Munro, E. & Odell, G. M. Robustness, flexibility, and the role of lateral inhibition in the neurogenic network. Curr. Biol. 12, 778–786 (2002).
  Article CAS PubMed Google Scholar
• Miesenbock, G. & Kevrekidis, I. G. Optical imaging and control of genetically designated neurons in functioning circuits. Annu. Rev. Neurosci. 28, 533–563 (2005).
  Article CAS PubMed Google Scholar
• Miesenbock, G. & Morris, R. G. New technologies. Curr. Opin. Neurobiol. 15, 557–559 (2005).
  Article CAS PubMed Google Scholar