Welcome to the Featherstone lab web site. We in the Featherstone Lab are working to understand how the brain forms functional connections and processes information.

The brain was not always recognized as an information-processing organ. Originally, the brain was assumed to be nothing more than 'head filler' -- perhaps a type of bone marrow. The ancient Egyptians, who so meticulously preserved most organs during mummification, threw away the brain. Eventually, about 500BC, Greek anatomists realized that the brain is the seat of thought and conscious experience. However, they generally viewed the brain as some sort of ‘hydraulic calculator’ – a bunch of tiny interconnected tubes and cavities that would trap sensory information and eventually push behavior out.

We now understand that the brain is composed of individual cells, and that information flow within the brain takes the form of electrical and chemical signals. Nonetheless, most people still generally think of the brain as a series of tiny information pathways. They call these tiny pathways ‘neural networks', or 'neural circuits’, because the majority of historical studies have focused on electrical transfer of information, which is generally (but not exclusively) propagated by neurons. Unfortunately, this focus on neural circuits ignores many types of brain chemical signaling, and minimizes the importance of glia (a cell type that makes up 90% of the brain but about which relatively little is known). So it’s a bit narrow minded. But it’s useful nonetheless, and has driven research in neuroscience for several decades (except during the late 20th century, when you weren't cool unless you were cloning something).

How do neural circuits work? When electrical information is passed from one neuron to another, it does so via specialized cell-cell junctions called ‘synapses’. Synapses are key information transfer and processing points. Instinct and memory are thought to reside within synapses. Almost all psychoactive drugs work by altering the function of synapses.

There are several types of synapse. The most common type of synapse in your brain is 'glutamatergic'. In this type of synapse, messages from one cell to another take the form of glutamate -- a small amino acid that is secreted by one cell (the 'presynaptic cell') and received via 'glutamate receptors' on another cell (the 'postsynaptic cell'). Glutamate is the voice by which brain cells speak to each other. Glutamate receptors are the ears by which they hear.

Most neurons form synapses with many other cells – thousands, in some cases. But information does not flow uncontrolled through this vast network of connections. Information flow depends on the relative strength of individual synapses. Some types of memory, for example, are formed because glutamatergic synapses get stronger. If those synapses weaken, the memory is lost. If a neuron synapses onto two different postsynaptic cells, information flow will be biased toward the cell with the stronger synapse. If this strong synapse gets weaker such that information flow to the two postsynaptic cells becomes balanced or even biased toward the other cell, it is like ‘flipping a switch’. Depending on the connections that the two different postsynaptic cells make, this simple change in synapse strength could lead to changes in perception, thought, and behavior.

Glutamatergic synapse strength is controlled, to a large extent, by the number of postsynaptic glutamate receptors. If there are more receptors, the synapse is stronger. If there are fewer receptors, the synapse is weaker. And if there are no receptors, it isn’t a functional synapse at all. In effect, the number of glutamate receptors at synapses controls the ‘wiring’ of your neural circuits.

So what controls the abundance of postsynaptic glutamate receptors at synapses? That’s what we’re trying to figure out here in the Featherstone lab. For our experiments, we use Drosophila mealogaster (fruit flies). Why do we use fruit flies? There are several reasons…

First, we think the best way to figure out the mechanisms controlling glutamate receptor abundance is to use genetics. By identifying genes, knocking out genes, and modifying gene expression, we can learn -– at a molecular level – how things work. Drosophila have been a premier ‘genetic model organism’ for a century. It is arguably faster and easier to identify and manipulate genes in Drosophila than it is in any other animal. In addition, the functions of many Drosophila genes have been highly conserved through evolution. Thus, the things we learn about genes in flies typically apply to other animals, including humans. For example: 75% of human disease genes, and 87% of human genes associated with mental retardation in particular, have equivalents in flies. Many human genes were named after fly genes, because the genes were first discovered in flies.

Drosophila also have glutamatergic synapses, and use glutamate receptors in their brains essentially the same way we do. Drosophila learning depends on the same particular type of glutamate receptor found to be critical for human learning. In addition, flies (and other insects) do something quite convenient with some of their glutamatergic synapses: They use them as neuromuscular junctions (synapses between motor neurons and muscles on the periphery of the animal, outside the dense tangle of brain tissue). This makes glutamatergic synapses in Drosophila particularly accessible for a variety of powerful experimental techniques, including electrophysiology, immunocytochemistry, laser-scanning confocal fluorescent microscopy, and electron microscopy (all of which we use).

Finally, Drosophila are amenable to sophisticated behavioral analyses. Flies interact extensively with their environment and other animals, relying on several different types of sensory modalities and motor mechanisms that are surprisingly similar to those used by mammals (like us). Flies explore, learn, fight, and make love. They even sleep. Do they dream? If so, what about?

In short, we: 1) tinker with the function or expression of individual genes, 2) watch the development of glutamatergic synapses in the intact organism throughout development, 3) monitor synaptic function with extremely high resolution (even down to the level of seeing the behavior of individual synaptic glutamate receptor proteins in real time), and 4) see how these molecular changes affect behavior.

To see what specific things we’re working on now and what we’ve figured out so far, see our Projects and Publications pages.