Italian neuroscientist Flavio Donato used to think he had a pretty good idea how our brain worked: as an “orderly mess” of neurons and synapses, with input and stimuli from the outside creating branches and pathways in our brains.
Then he built a brain.
“Basically, we’re studying the part of the brain that controls memory formation and navigation,” Donato said from his lab in Norway. A postdoctoral fellow at the Kavil Institute for Systems Neuroscience, Donato has devoted his work to the brain’s medial temporal lobe, a region that researchers haven’t completely figured out yet. Donato’s work in figuring out the medial temporal lobe not only earned him the 2017 Eppendorf & Science Prize for Neurobiology, it’s got neuroscientists rethinking everything they thought they knew about how our brain works.
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“This part of the brain is not really well known,” Donato explained. “There are a lot of neurons, and they work together to achieve the formation of memory. We wanted to see how this network comes together, and try to understand the logic by which they make synapses or connections with each other.”
Donato invented a startlingly simple new method. He and his team took pregnant rats and injected the brains of the rat fetuses with a virus, using the same infinitesimally small needles as doctors do in IVF procedures.
“We injected inside a specific area of the brain where neurons were born,” Donato clarified, “and we give a small genetic tag to the neurons that were born at the time. We were then able to label and follow their activity once those neurons established their connectivity.” Using sonogram technology, the team was able to see—for the first time—that the neurons in the entorhinal-hippocampal circuit are born in sequential order, from the top (dorsal) part of the brain down to the bottom (ventral) portion.
In other words, Donato was the first neuroscientist to see the birth of the network that gives rise to memory.
“What we found is that one of these neurons acted as sort of an orchestra director, starting the process of making this functional network,” he said. These cells, called stellate cells and embedded deep inside the brain, give a signal to the neurons in the entorhinal-hippocampal circuit to start firing and connecting, forming the basis of our memory. But the signal to start maturation is intrinsic—it comes from the stellate cells themselves, and not from any external trigger. Unlike the brain's sensory system, which needs external sensory stimulation such as light and touch for the neural network in that region to develop, the stellate cells do this “autonomously,” Donato explained.
“That signal is in [the stellate cells] from the date of birth. When humans are born, the clock starts ticking and the process just begins. The fact that we have these cells that don’t need an [external] signal to start maturation—we didn't think that was possible.”
Donato's research is primed to advance the study of memory-loss diseases like dementia and Alzheimer’s. Stellate cells are some of the first cells affected by cell death and plaque buildup when memory-loss diseases strike. Understanding that neurons mature sequentially, starting with the stellate cells in the deeper layers of the brain, allows scientists to potentially fix the problem before it moves on to other neurons.
“We now have the technology to understand how a neural circuit works,” Donato said, admitting that he's “excited” about the implications of his research. “If we understand how the brain works, then we can sooner understand how to fix it.”
