|Wulfram Gerstner (Ecole Polytechnique de Lausanne, Switzerland)
Title : Modeling synaptic plasticity – from synapses to function
Modeling synaptic plasticity has two major challenges: First, numerous electrophysiological experiments have shown that changes of synaptic connections depend on voltage, spike timing, firing rate as well as other factors and evolve on the time scale of milliseconds to hours. It would be desirable to have a model that covers all these aspects and accounts for synaptic plasticity as measured in slices. Second, the field of experimental and theoretical neuroscience is interested in synaptic plasticity because it has been linked to learning and memory formation. Therefore, a synapse model should also be functionally useful in large circuits, for example as a working memory. Typically, the two challenges are addressed separately: For example there are numerous models of induction of plasticity or models of working memory with fixed connectivity, but only few models that try to combine the plasticity with functional memory. In this talk, I will sketch how the two lines of research can be brought together.
|John Rinzel (New York University, USA)
Title : A neuromechanistic model for auditory streaming
I will describe results of our neuromechanistic modeling and psychoacoustic experiments on the perceptual dynamics of auditory streaming for a popular paradigm that relates to the phenomenon of sound source segregation, the cocktail party problem. The stimulus, a sequence of two interleaved tones, A and B, is ambiguous. Over minutes-long presentations, perception alternates between an integrated pattern and a segregated pattern of the two streams A_A_A_ and _B___B___ so called, perceptual bistability. Our dynamical model involves a competition network based on mutual inhibition, slow adaptation, and noise. It accounts for the statistics of the alternations and their dependence on the difference in tone frequencies. Our model also describes the effect of attention when subjects are instructed to hold one percept or the other. The prolongation of the attended percept durations is an emergent property of the network.
Title : The synapse, as a statistical nano-device: toward chemistry in cellulo
The efficiency and accuracy of neurotransmission strongly depends on two apparently antagonist properties of synaptic membrane: the stability of its organization and its ability to adapt to plasticity events. In addition, the structural stability of synapses has to be reconciled with the notion that cell membranes are fluid. Membrane molecules are compelled to move within the membrane surface due to thermal Brownian agitation, which favors the homogeneous distribution of the molecules. As a result, neurons spend energy to stop or reduce these movements, and maintain molecules in certain locations via mechanisms that decrease this fluidity. We investigate the regulation of synaptic receptors dynamics by the different (structural and functional) elements that make the synapse. We have approached these conceptual paradoxes by developing new technological and analytical tools that allow the monitoring of the behavior of synaptic components at the molecular level and change of the scale of analysis. We demonstrated rapid exchanges between synaptic and extra-synaptic receptors and we showed that transient stabilization of receptors at synapses occurs by interaction with partners, such as scaffold proteins. Novel super-resolution imaging methods (PALM, STORM) gave us a precise insight on the organization of these postsynaptic structures. Thus combination of single particle tracking and super-resolution methods, open access to molecular counting and energy involved in receptor-scaffold interactions as well as on and off rate of molecular interactions. Thus beyond super-resolution methods is chemistry “in cellulo” accounting for the regulation of receptor number and consecutively that of synaptic strength. Ultimately, the dynamic regulations of receptor-scaffold and scaffold–scaffold interactions appear as a central tenet for the maintenance and plasticity-related changes of receptor numbers at synapses. These processes are likely to be deregulated in pathological situations such as in neurodegenerative diseases.