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Genomics, Memory and Neuronal Evolution
The human brain is the most complex molecular machine known. It is composed of a hundred billion nerve cells, each of which is unique and makes innumerable connections with other nerve cells. Together these cells and all their connections allow us to move, think, dream, imagine and learn.
What if . . . we could understand how the brain does that and how this complexity has evolved? What if we could understand what has gone wrong with the brain when someone with Alzheimer’s or another dementia has lost the ability to learn and remember? It would seem that the best and the most efficient way to treat any disease is to understand the normal biology of a physiological process, cell or organ at the level of the genes that make it work. Understanding brain complexity starts with the most fundamental questions: What makes a neuron? What is the molecular “toolkit” needed to make a neuron in the first place? Is there only one or are there many “toolkits” to support the origin and maintenance of neural organization?
Comparative neurobiology suggests that there are many ways to make a neuron. Astonishingly, our analysis reveals that simplex brains might have independently evolved at least five to seven times during the 550 million years of animal evolution. The hypothesis we are testing is that the complex brains we find in representatives of existing animal phyla are the result of parallel evolution of different ancestral cell lineages. We want to reconstruct how the descendents of these cell lineages “come together” to form a brain in the octopus, or honey bee, or human. We are working on a broad spectrum of animals representing different levels of neural organization and tissue complexity: from the simplest sponges to molluscs (slugs, nautilus and octopus) and arthropods.
Another research goal is to understand the molecular mechanism of the formation and long-term maintenance of memories. Here, the sea slug Aplysia and related marine molluscs lead the way. Their giant nerve cells allow us to probe the critical molecular events of learning and memory in real time, all the way from genes to behaviors. In fact, we can follow the activity of all the genes in a single neuron as it learns and remembers!
In doing so we are asking questions which are difficult or impossible to address elsewhere. How does the activity of more than 20,000 genes within a single cell grow synapses and form memories that last a lifetime? Is there only one way, or are there multiple ways to do this and why? Since the genes and the way they are regulated in our brain cells are so similar to those in Aplysia, this understanding has tremendous potential application for diseases of the human brain and nervous system.
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