How Neurons Extend Their Tentacles: A Balance Between Length and Strength

Xiang Yu
Department of Psychiatry and Behavior Sciences
Stanford University
June 2002

Human brains contain billions of nerve cells, or neurons, in an intricate and precise network of connections. How does a neuron know which of its many neighbors to connect with? And how do these connections combine to form the greater entity of the thinking brain? My research in neuroscience tackles this problem by examining the molecules that regulate the growth and development of neurons. This research is important on two levels: first, it is fundamental for understanding how we process information, learn new things and store them in our memory. Second, many neurological disorders, such as autism and Down's and fragile-X syndromes, result from abnormalities in the development of neurons and neuronal connections. Understanding the basic mechanisms of neuronal development will help us understand how our brain works and shed light on the causes of some neurological disorders, providing clues to possible treatments.

A neuron is a nerve cell that extends long processes or branches. To use an analogy, if each neuron were an octopus, then the processes which extend from the center of the neuron would be the tentacles of the octopus: they are long and thin and are the means by which neurons contact other neurons. We can imagine the brain as a huge and three-dimensional field of octopi, all on top of each other and extending their tentacles to contact as many other octopi as possible. In the same way that octopi have suckers on their tentacle for grabbing objects, neuronal processes contact each other through specialized sites known as synapses. The precise pattern by which neurons contact each other through the synapses on their processes, forms the basis of information storage in the brain. How can such a large, complex and ever-changing network be built in a relatively simple manner? One approach would be for the many factors that influence the growth and development of neurons to act in different combinations, over different time scales, and at different locations. This way a finite number of factors can produce a virtually infinite number of unique combinations, just like ten digits can generate millions of potential lottery numbers.

My project focuses on understanding how one factor influences the way neurons develop and form connections with each other. This factor is a protein called beta-catenin, which is present at high levels in all neurons and is an important component of the synapse, the sucker through which neurons contact each other. My experiments are performed in an easy-to-manipulate system, namely rat neurons in a tissue culture dish. I observe changes in the appearance of the neurons and in the amount of protein present in the neurons using a microscope. To understand the normal function of beta-catenin, I alternately increase and decrease its levels above and below normal to observe the effects of these changes on the structural and functional properties of the cell. In terms of the octopus analogy, my results suggest that neurons with more tentacles have a decreased number of suckers per tentacle, as if the "octopus" has some mechanism for regulating the total number of contact sites it has. The reverse is also true for neurons with less tentacles, again maintaining the total number of suckers. This finding is very interesting because it suggests that neurons have some mechanism for balancing the length of their processes and the total number of synapses they make with other cells. In other words, the octopus strives to have long tentacles to reach objects further away from itself. However, since it has a finite amount of building material, it needs to optimize the length of its tentacles with the strength of the suckers on each tentacle such that a balance of strength and length is maintained: there is no point in have long floppy tentacles which cannot grab objects, or having strong suckers close to the head where they cannot reach out to the surroundings. I believe that the answers to these basic questions in neuroscience will help us understand how our brain works and what goes wrong in neurological disorders where the normal patterns of synapses and neuronal connections go awry.