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Karolinska Research Lectures – Eve Marder

Research Lecture at NOBEL FORUM
17 March, kl. 16.30
Free admission

Eve Marder, PhD, Professor of Biology

Volen Center for Complex Systems, Brandeis University , Waltham, MA 02454-9110, USA

https://blogs.brandeis.edu/marderlab/

Title: “Robustness, Variability, Modulation, and Homeostasis in 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?  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 (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 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) 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.

 

Host:  Christian Broberger

Dept. of Neuroscience, Karolinska Institutet

Tel. 08- 524 87038; christian.broberger@ki.se

http://www.neuro.ki.se/broberger/html


Contact:
Tatiana Goriatcheva

Nobelkansliet, Nobel Forum,

Tel. 08-524 87805, tatiana.goriatcheva@nobel.se

For press already registered to attend the Nobel Lectures, December 7, Aula Medica

For press already registered to attend the Nobel Lectures in Physiology or Medicine, December 7, Aula Medica, Nobels väg 6, Karolinska Institutet.

Individual accreditations are mandatory for media representatives due to limited space in the media section (registration now closed).

Press badge needed for entrance to the Aula Medica Lecture hall on the 7th of December. The Press badge must be picked up at the Reception Desk, Nobel Forum, Nobels väg 1, between 10:00 and 12:00, December 7th, or on December 6th from 13.00-15.30.

Press are asked to arrive at Aula Medica at the latest 12:00 to have time to set up equipment and be seated in time for the lectures.

Information regarding the Press Conference on December 6th and the Nobel Lectures on December 7th

Press Conference on December 6th, at 14:00, Nobel Forum, Nobels väg 1

On December 6th, a Press Conference with this year’s Nobel Laureates will be held for media and press representatives only.

Space is limited and individual registration and press accreditions are mandatory.

Register below.

Nobel Lectures on December 7th, at 13:00, Aula Medica, Nobels väg 6

The official Nobel Lectures held by this year’s Nobel Laureates in Physiology or Medicine are held on December 7th.

For the general public: For the general public there is no registration required and the limited seating are accomodated according to the first come, first served basis. No large bags or camera equipment are allowed in Aula Medica except in the media section. Live bradcasting available at http://www.nobelprize.org and  live streaming to a nearby lecture hall.

For press: To get access and seating to the press section you need to register and get press accreditation. Please use the link below to register.

  • Large bags or camera equipment not allowed in Aula Medica (except in media section, follow instructions on registration page to be approved permission).
  • Individual accreditations are mandatory for media representatives due to limited space in the media section.
  • Press are asked to arrive at Aula Medica at the latest 12:00 to  have time to set up equipment and be seated in time for the lectures.
  • Press badge needed for entrance to the Aula Medica Lecture hall on the 7th of December must be picked up at the Reception Desk, Nobel Forum, Nobels väg 1, between 10:00 and 12:00, December 7th.

Register below.

Karolinska Research Lecture – Huda Zoghbi

Karolinska Research Lectures at NOBEL FORUM

November 5, 16.30, Free admission

Speaker: Huda Y. Zoghbi

Jan and Dan Duncan Neurological Research Institute, at Texas Children’s Hospital, Houston, USA

Lab webpage:  https://www.bcm.edu/research/labs/huda-zoghbi

Titel: Lessons in neuronal function from Rett syndrome and related disorders

Rett Syndrome is a fascinating disease for scientists and an unmitigated tragedy for parents: children are apparently healthy for the first year or two after birth, then abruptly—over a matter of weeks—lose acquired motor and cognitive skills, stop speaking, and gradually develop a host of unsettling features such as respiratory dysrhythmias, stereotypic hand-wringing or hand-flapping, constant crying, and seizures. Although the presentation varies widely, the disease seems to affect virtually all brain regions. The genetic basis of this strange disease is loss of function mutations in the X-linked gene MECP2, which encodes Methyl-CpG-binding protein 2 (MeCP2). We have used genetic, behavioral, physiological, anatomical, and molecular approaches to interrogate the pathogenesis of Rett and other disorders involving either loss of MeCP2 function or duplication of the MECP2 region. Although many questions remain unanswered about the precise activities of this protein, one thing is absolutely clear: the brain is exquisitely sensitive to MeCP2 levels. Even modest decreases or modest increases in the protein levels cause neuropsychiatric phenotypes. I will discuss recent work that sheds light on the roles MeCP2 serves in neurons, how it orchestrates an epigenetic program that alters chromatin architecture to influence neuronal network activity and excitatory/inhibitory balance, and the effects of manipulating either MeCP2 levels or the network in animal models.

 Host: Sandra Ceccatelli och Tomas Hökfelt, Karolinska Institutet

Contact: tomas.hokfelt@ki.se

Contact:Tatiana Goriatcheva, Nobel Office, Nobel Forum,

tel. 524 87805, tatiana.goriatcheva@nobel.se