OPTO-FUSI: EMBRACING THE COMPLEXITY OF THE BRAIN

30 April 2021 - Research

When you spot danger, you better act—fast! A team of researchers led by Karl Farrow and Alan Urban from NERF sheds new light on how the brain processes visual information to guide behavior. By combining optogenetics with functional ultrasound imaging in a so called opto-fUSI method, they were able to reveal the networks in the brain that are active when animals try to avoid danger. The results have been published in this week’s edition of Neuron.

Processing visual cues

How do different cells in the brain collaborate to guide behavior? This question drives neuroscientist Karl Farrow from Neuro-Electronics Research Flanders (NERF) in Leuven, Belgium. Farrow’s team studies the communication lines that connect what our eyes perceive with how we behave in response. They are particularly interested in the neurons of the superior colliculus.

The superior colliculus—Latin for "upper hill"— is a brain structure named based on its anatomical location: at the top of the mammalian midbrain. Neurons in the superficial layers of this brain area receive direct input from the retina and distribute this information about the visual world throughout the brain to guide attention and generate behavior.

Farrow

Fight or flight

Farrow: “Any of the computations performed by the nervous system can be interpreted as answers to particular challenges that we – or any animal for that matter – are faced with. What my lab wants to understand is how neural circuits are organized to link specific sensory inputs with the activation of appropriate behaviors.”

In a biological context, appropriate behaviors entail for example the arrest or flight behavior of small rodents when spotting an avian predator. Scientists have uncovered that activation of distinct types of neurons in the superior colliculus leads to such specific behaviors, but our view of the downstream information processing remains limited.

Opto-fUSI

To address this, Karl Farrow teamed up with NERF colleague Alan Urban, who co-developed the opto-fUSI technique. Urban: “The new technology that we developed here is a significant advance when it comes to analyzing the brain in action. For the first time, we can combine high-resolution imaging of brain activity at large scale with targeted manipulations of specific brain circuits in small mammals.”

Using opto-fUSI, the researchers mapped the network of brain regions that are activated by four different cell types of the superior colliculus. “We analyzed the activity of 264 areas across the mouse brain,” says Anna Chrzanowska, PhD student in the Farrow lab. “Our results indicate that the neural pathways involved in mediating defensive behaviors are far more widely distributed than previously reported.”

Anna And Arnau

Brain-wide networks

“We found that each of the neuronal groups in the superior colliculus triggered different behaviors and activated dozens of brain areas across the brain. These large networks were distinct, but partially overlapping,” adds Arnau Sans-Dublanc, a PhD student in the labs of Farrow and Urban. “This included regions not previously thought to mediate defensive behaviors.”

“By combining fUSI with optogenetics, we provide one of the first brain-wide views of how cell-types of the superior colliculus disseminate information across the brain to guide behavior,” says Arnau Sans-Dublanc.

“Our results show the potential of this technique to observe the functional downstream networks of any cell-type in the brain of small mammals in an unbiased manner. We believe this will allow us to understand how different brain regions act in concert to guide behavior under a variety of conditions and where it goes wrong in disease.”

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Optogenetic fUSI for brain-wide mapping of neural activity mediating collicular-dependent behaviors
Sans-Dublanc, Chrzanowska et al. 2021 Neuron
Opto Fusi Singleimage
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