Robustness, degeneracy and neuromodulation of neurons and networks

6 November 2015

Eve Marder
Volen Center for Complex Systems
Brandeis University


All individual humans and animals are different. How well-tuned do brains need to be to produce behavior that we consider healthy and normal? This question has been difficult to study rigorously in animals with large brains, but small nervous systems with identified neurons and circuits have allowed us to ask this question in the past few years. Experimental work on the crustacean stomatogastric ganglion (STG) has revealed a 2-6 fold variability in many of the parameters that are important for circuit dynamics. These include the strength of the same synapse across animals, as well as the conductance densities of many membrane currents and the copy numbers of the mRNA that encode those currents [1]. At the same time, a body of theoretical work shows that the similar network performance can arise from diverse underlying parameter sets [2, 3]. Together, these lines of evidence suggest that each individual animal has found a different solution to producing "good enough" motor patterns for healthy performance in the world. These findings raise the question of the extent to which animals with different sets of underlying circuit parameters can respond reliably and robustly to perturbations. Consequently, we studied the effects of temperature and neuromodulation on the pyloric rhythm of crabs. Temperature is a global perturbation that influences every membrane current differently. Nonetheless, we find that all animals respond reliably and robustly to changes in temperature that mimic those the animals ordinarily encounter in their environment [4], but more extreme temperature perturbations "crash" the network, resulting in a loss of rhythmic activity [5, 6]. Each individual "crashes" in different ways, consistent with the underlying variability in parameter structure. Moreover, neuromodulation alters the sensitivity of the networks to temperature, suggesting that one function of neuromodulation may be to enhance robustness to some kinds of perturbations.

Neurons and networks must constantly rebuild themselves in response to the continual and ongoing turnover of all of the ion channels and receptors that are necessary for neuronal signaling. A good deal of work argues that stable neuronal and network function arises from homeostatic negative feedback mechanisms. Nonetheless, while these mechanisms can produce a target activity or performance, they are also consistent with a good deal of recent theoretical and experimental work that shows that similar circuit outputs can be produced with highly variable circuit parameters. I will describe new computational models [7, 8] for cellular homeostasis that give insight into a variety of experimental observations, including correlations in the expression of ion channel genes. In response to perturbation these homeostatic models usually compensate for perturbations, but some perturbations elude compensation. Moreover, situations can arise in which the homeostatic mechanisms result in aberrant behavior, such as may occur in disease.


  1. Goaillard, Taylor, Schulz, Marder, "Functional consequences of animal-to-animal variation in circuit parameters", Nat Neurosci 12:1424-30 2009. PubMed
  2. Prinz, Bucher, Marder, "Similar network activity from disparate circuit parameters", Nat Neurosci 7:1345-52 2004. PubMed
  3. Gutierrez, Marder, "Rectifying electrical synapses can affect the influence of synaptic modulation on output pattern robustness", J Neurosci 33:13238-48 2013. PubMed
  4. Tang, Goeritz, Caplan, Taylor, Fisek, Marder, "Precise temperature compensation of phase in a rhythmic motor pattern", PLoS Biol 8:e1000469 2010. PubMed
  5. Tang, Taylor, Rinberg, Marder, "Robustness of a rhythmic circuit to short- and long-term temperature changes", J Neurosci 32:10075-85 2012. PubMed
  6. Rinberg, Taylor, Marder, "The effects of temperature on the stability of a neuronal oscillator", PLoS Comp Biol 9:e1002857 2013. PubMed
  7. O'Leary, Williams, Caplan, Marder, "Correlations in ion channel expression emerge from homeostatic tuning rules", PNAS 110:E2645-54 2013. PubMed
  8. O'Leary, Williams, Franci, Marder, "Cell types, network homeostasis, and pathological compensation from a biologically plausible ion channel expression model", Neuron 82:809-21 2014. PubMed

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