Visual Stimuli

Brain Blood Flow Syncs with Visual Stimuli

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Summary: Researchers pioneered a new method to monitor blood vessel dynamics in the mouse brain, revealing that visual stimuli can synchronize vasomotion, potentially improving brain function. By exposing mice to a specific pattern of horizontally moving stripes, the team observed that vasomotion matched the stimulus pattern’s speed and spread throughout the brain.

This synchronization suggests a mechanism by which the brain enhances its circulation of nutrients and clears waste, possibly boosting cognitive abilities. The findings could have implications for treating and preventing neurological conditions.

Key Facts:

  1. Innovative Monitoring Technique: The study introduces a novel method to observe blood vessel dynamics through the intact skull or deep within the brain using optical fibers.
  2. Vasomotion Synchronization: Visual stimuli can entrain the brain’s vasomotion, leading to synchronized blood vessel activity that enhances nutrient delivery and waste removal across the entire brain.
  3. Potential Health Benefits: This synchronized vasomotion may improve learning, aid in stroke recovery, and potentially delay neurodegenerative diseases like dementia by improving the brain’s metabolic efficiency.

Source: Tohoku University

Compared with computers, the brain can perform computations with a very low net energy supply. Yet our understanding surrounding how the biological brain manages energy is still incomplete.

What is known, however, is that the dilation and constriction cycles of blood vessels, or vasomotion, spontaneously occur in the brain, a process that likely contributes to enhancing the circulation of energetic nutrients and clearing wasteful materials.

Now, researchers from Tohoku University have developed a method that easily observes and monitors blood vessel dynamics in the mouse brain. This can be done either through the intact skull of a mouse, or deep into the brain using an implanted optical fiber.

Since it has been reported that sensory stimuli can cause dilation of blood vessels or hyperemia, researchers sought to induce vasomotion via presenting mice with visual stimuli.

What they discovered was when a mouse was shown a horizontally moving stripe pattern that changed direction every 2 to 3 seconds, it caused a reaction in the mouse’s blood vessels that matched the pattern’s speed.

Mice were presented with 15-minute visual training sessions interleaved with 1-hour resting periods for 4 times per day. With such spaced training, the amplitude of the synchronized vasomotion gradually increased.

Interestingly, the visually induced vasomotion was not confined to the area of the cerebral cortex responsible for visual information processing. In other words, synchronized vasomotion spread throughout the whole brain.

“Synchronized vascular motion can be entrained with slowly oscillating visual stimuli,” says Professor Ko Matsui of the Super-network Brain Physiology lab at Tohoku University, who led the research.

“Such enhancement of circulation mechanisms may benefit the information processing capacity of the brain.”

While it’s long been known that changes in neuron connections support learning and memory, the plasticity of vasomotion hasn’t been described before.

Matsui and his colleagues found that a specific visual pattern makes the eyes move more, and this eye movement improvement depends on changes in the brain’s cerebellum. The researchers also observed that blood vessel activity in the cerebellum synchronized with this optokinetic motor learning.

Lead study investigator, Daichi Sasaki, believes that synchronized vasomotion, which efficiently delivers oxygen and glucose, could improve learning abilities

He states, “Our next step is to explore the advantages of vasomotion synchronization. It might help clear waste like amyloid beta, potentially delaying or preventing dementia.

“Stroke recovery could also benefit from better energy supply and waste removal. Additionally, synchronized vasomotion might even enhance intelligence beyond our natural capabilities.”

Human Brain Organoids Implanted Into Mouse Cortex Respond to Visual Stimuli for First Time

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A team of engineers and neuroscientists has demonstrated for the first time that human brain organoids implanted in mice have established functional connectivity to the animals’ cortex and responded to external sensory stimuli.

The implanted organoids reacted to visual stimuli in the same way as surrounding tissues, an observation that researchers were able to make in real time over several months thanks to an innovative experimental setup that combines transparent graphene microelectrode arrays and two-photon imaging. 

The team, led by Duygu Kuzum, a faculty member in the University of California San Diego Department of Electrical and Computer Engineering, details their findings in the Dec. 26 issue of the journal Nature Communications.

Kuzum’s team collaborated with researchers from Anna Devor’s lab at Boston University; Alysson R. Muotri’s lab at UC San Diego; and Fred H. Gage’s lab at the Salk Institute.

Human cortical organoids are derived from human induced pluripotent stem cells, which are usually derived themselves from skin cells. These brain organoids have recently emerged as promising models to study the development of the human brain, as well as a range of neurological conditions. 

But until now, no research team had been able to demonstrate that human brain organoids  implanted in the mouse cortex were able to share the same functional properties and react to stimuli in the same way. This is because the technologies used to record brain function are limited, and are generally unable to record activity that lasts just a few milliseconds. 

The UC San Diego-led team was able to solve this problem by developing experiments that combine microelectrode arrays made from transparent graphene, and two-photon imaging, a microscopy technique that can image living tissue up to one millimeter in thickness.  

“No other study has been able to record optically and electrically at the same time,” said Madison Wilson, the paper’s first author and a Ph.D. student in Kuzum’s research group at UC San Diego. “Our experiments reveal that visual stimuli evoke electrophysiological responses in the organoids, matching the responses from the surrounding cortex.” 

The researchers hope that this combination of innovative neural recording technologies to study organoids will serve as a unique platform to comprehensively evaluate organoids as models for brain development and disease, and investigate their use as neural prosthetics to restore function to lost, degenerated or damaged brain regions. 

“This experimental setup opens up unprecedented opportunities for investigations of human neural network-level dysfunctions underlying developmental brain diseases,” said Kuzum. 

Kuzum’s lab first developed the transparent graphene electrodes in 2014 and has been advancing the technology since then. The researchers used platinum nanoparticles to lower the impedance of graphene electrodes by 100 times while keeping them transparent. The low-impedance graphene electrodes are able to record and image neuronal activity at both the macroscale and single cell levels. 

By placing an array of these electrodes on top of the transplanted organoids, researchers were able to record neural activity electrically from both the implanted organoid and the surrounding host cortex in real time. Using two-photon imaging, they also observed that mouse blood vessels grew into the organoid providing necessary nutrients and oxygen to the implant. 

Researchers applied a visual stimulus–an optical white light LED–to the mice with implanted organoids, while the mice were under two-photon microscopy. They observed electrical activity in the electrode channels above the organoids showing that the organoids were reacting to the stimulus in the same way as surrounding tissue.

The electrical activity propagated from the area closest to the visual cortex in the implanted organoids area through functional connections. In addition, their low noise transparent graphene electrode technology enabled electrical recording of spiking activity from the organoid and the surrounding mouse cortex. Graphene recordings showed increases in the power of gamma oscillations and phase locking of spikes from organoids to slow oscillations from mouse visual cortex. 

This shows neurons
Researchers were able to detect and image the border between a transplanted human brain organoid and mouse brain. Credit: Madison Wilson/UC San Diego

These findings suggest that the organoids had established synaptic connections with surrounding cortex tissue three weeks after implantation, and received functional input from the mouse brain. Researchers continued these chronic multimodal experiments for eleven weeks and showed functional and morphological integration of implanted human brain organoids with the host mice cortex. 

Next steps include longer experiments involving neurological disease models, as well as incorporating calcium imaging in the experimental set up to visualize spiking activity in organoid neurons. Other methods could also be used to trace axonal projections between organoid and mouse cortex. 

“We envision that, further along the road, this combination of stem cells and neurorecording technologies will be used for modeling disease under physiological conditions; examining candidate treatments on patient-specific organoids; and evaluating organoids’ potential to restore specific lost, degenerated or damaged brain regions,” Kuzum said.