Speaker of Workshop 1
Will talk about: Making the connectome work: Lessons from simple systems
Vladimir Brezina is an Associate Professor at the Mount Sinai School of Medicine. His research focuses on the central pattern generating and neuromuscular circuits that participate in various feeding behavior of the mollusc Aplysia. For example, their output is controlled, both centrally and in the periphery, by complex local networks of interacting neuromodulators. The experimentally advantageous Aplysia system permits the cellular effects of the modulators to be dissected, using such techniques as voltage and patch clamp, optical recordings of contractions of single muscle fibers, and intracellular calcium measurements. The effects can then be functionally reconstructed in the behavioral context in semi-intact and intact preparations, and understood conceptually with the use of realistic as well as more abstract mathematical modeling techniques. The goal is to understand not just the Aplysia system but to derive from it more general principles governing the operation of such control mechanisms in biological systems.
Great progress is being made in mapping the neuronal wiring diagrams—the connectomes—of nervous systems. It is hoped by some researchers that once the full complement of the connections has been mapped, reassembling the connections in a model of the nervous system will allow the “emergent” properties of the nervous system to manifest themselves: the brain will simply work. Yet we already have connectomes mapped at the level of the individual neurons for some simple circuits, such as the crustacean stomatogastric ganglion, and even the complete connectome for one entire nervous system, that of the nematode worm Caenorhabditis elegans, and from none of these connectomes has the function of the brain simply emerged. These simple systems have enabled analysis of this failure. I will discuss in particular one cause of the failure. In these simple systems, it has become clear that the static connectome is dynamically modified and supplemented by multiple actions of neuromodulators—neurotransmitters, neuropeptides, diffusible gaseous messengers—that can be so complex that they can be thought of as constituting a biochemical network that combines with the neuronal network of the connectome to perform the computations of the nervous system. Thus the connectome alone is not sufficient to specify, and permit us to understand, the computations that underlie behavior. In my presentation I will discuss this and other lessons that simple systems offer for making more complex connectomes, including that of the human brain, work.