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Posted: May 12, 2017
Brain-on-a-chip built on nanowire scaffolds
(Nanowerk Spotlight) Neurons are the basic computational units or cells in the brain and they form connections between other neurons to form neuronal circuits. When these neurons are at work in the brain – during learning, thinking, sensing, etc – they pass off information from one neuron to the other via their synaptic interconnects.
Understanding how the brain works and how circuits are formed remains a grand challenge in neuroscience.
Growing neurons outside the brain but with predictable synaptic connectivity between other neurons could provide for an efficient platform for fundamental research and design of neuroprosthetics.
Providing an environment were scientists could study a less complex neuronal circuit as opposed to a fully functioning circuit in a living mammalian brain will open up a new experimental paradigm of understanding how the neurons are influenced by the mechanical properties of the brain as they grow and form circuits.
"Using this platform, we can engineer the neurons' morphologies and make them connect to each other in a more predictive way," Dr. Vincent Daria, Group Leader (Neurophotonics Group) at the ANU College of Medicine, Biology and Environment, tells Nanowerk. "The geometry of the nanowire scaffolds emulates the mechanical properties of the brain environment so the neurons could function appropriately."
The team's paper is the first demonstration of growing neurons on Indium Phosphide (InP) semiconductor nanowires. InP is special type of semiconductor which responds to light, making it appropriate for opto-electronic interface with neurons.
Though it will not provide the most accurate representation of the brain, this new platform will nonetheless allow to study circuit formation, function (and dysfunction) in a more controlled manner.
The organization of the nanowires could define the morphology of the neurons and its neurites. The neurites (dendrites and axons) of the neurons uses the isotropic arrangement of vertically aligned InP nanowires as scaffolds for their growth.
neuron from cortical culture after 2 days in vitro. The inset on the left show a fluorescence image of the cellular network that formed on the edge of the nanowires. The inset on the lower right depicts a closer view around the axon. (Image: Daria Research Group) (click on image to enlarge)
"Using a particular nanowire geometry, we have shown that the neurons are highly interconnected and predictably form functional circuits," notes Daria.
He points out that using semiconductor nanowires as scaffolds can be a platform for brain-machine interface. Hence, this work will provide new insights into the development of neuroprosthetics – devices that supplant or supplement the input and/or output of the nervous system.
Unlike other prosthetics (e.g. artificial limbs), neurons need to connect synaptically which form the basis of information processing in the brain during sensory input, cognition, learning and memory. It therefore is important to build up the appropriate environment where these neurons can be predictably connected into functional circuits and not merely adjacent cells that donít talk to each other.
"The most exciting part of this work is the fact that we were able to make predictive connections between the neurons and demonstrated them to be functional with neurons firing synchronously," says Daria. "In prior works, people have guided the growth of neurons and even made them visually forming circuits; but none of the prior works have shown that their circuits were functional."
He adds that, from a fundamental perspective, identifying the ideal geometry of the scaffolds could lead to our understanding of how neurons grow and how neuronal circuits are formed.
"We could explore how circuit function is influenced by the physical properties of the environment where neurons grow." "On the other hand, from an applications view, semiconductor nanowires provide for an excellent interface between neurons and electronic circuits for potential use as brain-machine interface or for building neuroprosthetics."
Going forward, the researchers aim to design scaffolds so they could emulate circuit formation and function of certain regions in the brain (e.g. cortex).
They also plan to study the synaptic connections formed naturally. In addition, they will try to induce more connections (or program the neuronal circuit) via optogenetics and patterned optical stimulation.
"The main challenge is to understand how circuits in the brain are formed following the establishment of synaptic connections between neurons," concludes Daria. "By introducing artificial scaffolds that mimic certain brain regions, we aim to correlate our findings with real circuits in the brain."