eWEAR: To understand human brain imaging, Stanford scientists look to flies
Meeting Reports
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Nov 13, 2022
Functional magnetic resonance imaging (fMRI) is their most essential tool, and they use it to observe how activity in brain regions ebbs and flows. But fMRI can’t actually measure the electrical firing of individual neurons—instead, it watches for increases and decreases in the flow of blood across the brain.
Neurons consume energy when they fire; and to produce usable energy in the form of ATP, cells need oxygen; and blood is what carries oxygen throughout the body. It isn’t difficult to imagine, therefore, that the brain regions with the most blood flow might also be the most active, and results from across neuroscience have supported the validity of this approach. fMRI measurements are closely correlated with the local field potential, an electrical signal that reflects the activity of small populations of neurons. And by studying slices of the brain under a microscope, researchers have been able to observe a tight relationship between cell firing and the production of ATP. But the link between energy metabolism and neuronal activity had not been directly observed at fast timescales in a living animal. To bridge that gap, a group of neurobiologists at Stanford University - Kevin Mann, Stephane Deny, Prof. Surya Ganguli, and Prof. Tom Clandinin - decided to look at flies.
Flies may seem a bizarre place to search for clues about the workings of a technology used to study humans. But Clandinin says that metabolism is such an evolutionarily ancient process that information about fly brain metabolism—on the cellular level, at least—is relevant to the human brain. “How neural activity might be correlated with glucose metabolism and energy production—that’s all stuff that’s evolutionarily common between flies and humans,” he says
And flies have some enormous advantages as experimental animals. They are tiny, reproduce quickly, and have relatively well-understood brains—and they are easy to genetically manipulate. To examine metabolism and neuronal activity at the same time, the researchers engineered their flies to produce two proteins that, by emitting different amounts of light, indicated changes in neuronal firing or ATP levels. So just looking at the fly brains was enough to determine how neuronal activity affected ATP levels. Using this technique, the researchers found that neuron firing and ATP levels were indeed correlated, and the results of their experiments were published in Nature last year.
Functional magnetic resonance imaging (fMRI) is their most essential tool, and they use it to observe how activity in brain regions ebbs and flows. But fMRI can’t actually measure the electrical firing of individual neurons—instead, it watches for increases and decreases in the flow of blood across the brain.
Neurons consume energy when they fire; and to produce usable energy in the form of ATP, cells need oxygen; and blood is what carries oxygen throughout the body. It isn’t difficult to imagine, therefore, that the brain regions with the most blood flow might also be the most active, and results from across neuroscience have supported the validity of this approach. fMRI measurements are closely correlated with the local field potential, an electrical signal that reflects the activity of small populations of neurons. And by studying slices of the brain under a microscope, researchers have been able to observe a tight relationship between cell firing and the production of ATP. But the link between energy metabolism and neuronal activity had not been directly observed at fast timescales in a living animal. To bridge that gap, a group of neurobiologists at Stanford University - Kevin Mann, Stephane Deny, Prof. Surya Ganguli, and Prof. Tom Clandinin - decided to look at flies.
Flies may seem a bizarre place to search for clues about the workings of a technology used to study humans. But Clandinin says that metabolism is such an evolutionarily ancient process that information about fly brain metabolism—on the cellular level, at least—is relevant to the human brain. “How neural activity might be correlated with glucose metabolism and energy production—that’s all stuff that’s evolutionarily common between flies and humans,” he says
And flies have some enormous advantages as experimental animals. They are tiny, reproduce quickly, and have relatively well-understood brains—and they are easy to genetically manipulate. To examine metabolism and neuronal activity at the same time, the researchers engineered their flies to produce two proteins that, by emitting different amounts of light, indicated changes in neuronal firing or ATP levels. So just looking at the fly brains was enough to determine how neuronal activity affected ATP levels. Using this technique, the researchers found that neuron firing and ATP levels were indeed correlated, and the results of their experiments were published in Nature last year.
