Studying the brains of fruit flies may offer insights into how human brain diseases develop, writes ANTHONY KING
I T MIGHT seem improbable that the fruit fly, Drosophila, with its brain the size of a pinhead could tell us anything about the human brain. Yet the fly has been a mainstay of laboratory research for decades and is helping a team at Trinity College Dublin to learn how the human brain works. Their stud may also deliver new insights into autism.
Inside the fly room at the college, Prof Mani Ramaswami holds up racks of vials containing fruit flies. The laboratory is home to half a million fruit flies in 500 different variants of the bug. These flies have been maintained as laboratory stock for decades and wouldn’t survive in the wild.
They are of use because their brains are similar to ours in how they work, though not in size.
Our brains contain billions of neurons, and each is linked to between 1,000 and 10,000 other neurons. These connections, or synapses, change when memories form. The same processes work in the fruit fly, though it has only 200,000 brain cells.
“[The fruit fly] is simple enough to understand, but complex enough to have many of the physiological, cognitive and developmental mechanisms of humans in recognisable form,” says Ramaswami. An olfactory neuron in the fruit fly has an equivalent in mammals, so we can predict the same processes will occur in humans, he adds.
The neuroscientists have gained insights into what happens in the brains of fruit flies as they form memories. This has relevance to our own memories and conditions, they say.
It is possible to ask how various genes that underlie neuropsychiatric diseases, such as autism, function in the memory circuits, says Ramaswami. “The work we are doing has relevance to autism, schizophrenia and other forms of psychiatric disease and the mechanisms for memory,” he says.
Ramaswami’s group at the college is focusing on a simple form of memory called habituation. “The first time you see something, you respond strongly to it, but if it’s repeated without anything interesting added, then you stop responding,” says Ramaswami.
A simple example is how our skin responds to clothing. Generally, we are not conscious of the feel of the clothing but we can become aware of it by thinking about it. This shows that sensory neurons are still sensing it, but a filtering mechanism in the brain blocks out such a constant stimulus. This filtering can go awry in some neuropsychiatric conditions, Ramaswami explains.
The fruit flies in the Trinity experiments are habituated to odours. How long they remember depends on the training procedure, says Ramaswami.
“If a fly smells an odour for 20 minutes or so you get habituation and it stops responding to the odour for an hour or so,” he says. If it smells it for days, long-term habituation sets in and the odour won’t be registered for three to five days.
The brain circuits in flies are the same for short-term and long-term habituation, says Ramaswami. “In one case the existing synapses become stronger or weaker and in the other case the synapses change physically, with more forming or some being removed,” he says. If a smell is exciting, an additional neuron joins in to modulate the experience and mark it as memorable. If a smell becomes overpowering, an inhibitory neuron dampens the response.
Dr Adrian Dervan routinely opens the brains of fruit flies in the Trinity lab and watches how neurons react when puffs of odour are blown over the antennae before and after they are habituated. Other researchers probe individual cells in the brain. DNA technology and gene manipulation are also used. The hope is that their work will contribute to therapy, though there is no certainty of that.
Ramaswami was a professor in the US before moving to Ireland five years ago. Science Foundation Ireland funds his work and he collaborates with Prof Veronica Rodrigues, a Trinity alumnus in the National Centre for Biological Sciences in Bangalore, India.