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Eve Marder

 

 

Wednesday 29th June 2016

Time: 4.00pm

 

Ground Floor Seminar Room

25 Howland Street, London, W1T 4JG

 

Robustness, Degeneracy and Neuromodulation of Neurons and Networks.

 

All individual humans and animals are different. How well-tuned do brains need to be to produce behavior that we consider healthy and normal? 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 (Goaillard et al., Nat Neuroscience. 2009). At the same time, a body of theoretical work shows that the similar network performance can arise from diverse underlying parameter sets (Prinz et al., Nat Neuroscience 2004; Gutierrez and Marder, 2013). 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, pH, 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 (Tang et al PLos Biol 2010), but more extreme temperature perturbations “crash” the network, resulting in a loss of rhythmic activity (Tang et al, 2012; Rinberg et al., 2013). 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 (O’Leary et al., PNAS 2013; Neuron et al, 2014; in preparation) 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. These models lead to a method to understand how animals can arise at solutions that are robust to temperature and modulation.

Bio:
Eve Marder is the Victor and Gwendolyn Beinfield Professor of Neuroscience in the Biology Department of Brandeis University. Marder was President of the Society for Neuroscience in 2008, and served on the NINDS Council, numerous Study Sections, and a variety of Advisory Boards for institutions in the USA and abroad. Marder is a member of the National Academy of Sciences, the National Academy of Medicine, the American Academy of Arts and Sciences, a Fellow of the Biophysical Society, a Fellow of the American Physiological Society, and a Fellow of the American Association for the Advancement of Science. She received the Miriam Salpeter Memorial Award for Women in Neuroscience, the W.F. Gerard Prize from the Society for Neuroscience, the George A. Miller Award from the Cognitive Neuroscience Society, the Karl Spencer Lashley Prize from the American Philosophical Society, an Honorary Doctorate from Bowdoin College, the Gruber Award in Neuroscience, and the Education Award from the Society for Neuroscience. Marder served on the NIH working group for the Obama BRAIN Initiative. Most recently, she will share the 2016 Kavli Award in Neuroscience.

Marder studies the dynamics of small neuronal networks, and her work was instrumental in demonstrating that neuronal circuits are not “hard-wired” but can be reconfigured by neuromodulatory neurons and substances to produce a variety of outputs. For the past 25 years Marder’s lab has combined experimental work with insights from modeling and theoretical studies. Together with Larry Abbott, her lab developed the programmable dynamic clamp, now used widely in laboratories around the world. Her lab pioneered studies of homeostatic regulation of intrinsic membrane properties, and stimulated work on the mechanisms by which brains remain stable while allowing for change during development and learning. Marder is now studying the extent to which similar network performance can arise from different sets of underlying network parameters, opening up rigorous studies of the variations in the individual brains of normal healthy animals.