Lifeboat Foundation: Safeguarding Humanity
Toggle light / dark theme

Blog

Category: neuroscience

‘Mob breaker’ TRIM37 prevents abnormal cell division by eliminating extra spindle poles

In 2000, researchers discovered that mutations that inactivate a gene known as TRIM37 cause a developmental disease called Mulibrey nanism. The extremely rare inherited disorder leads to growth delays and abnormalities in several organs, causing afflictions of the heart, muscles, liver, brain and eyes. In addition, Mulibrey nanism patients exhibit high rates of cancer and are infertile.

In 2016, UC San Diego School of Biological Sciences researchers in the labs of Professors Karen Oegema and Arshad Desai began understanding how TRIM37, when operating normally, plays a key role in preventing conditions that lead to Mulibrey nanism. They linked TRIM37 to spindles, which separate chromosomes during , and centrosomes, the spherical organizing structures at each end of spindles.

The image above shows a normal mitotic cell (left) compared to a cell lacking TRIM37 (right), with spindle microtubules (green), centrosomal protein centrobin (magenta) and DNA (white). Normal cells have two spindle poles that ensure proper cell division. Cells lacking TRIM37 frequently have extra spindle poles, containing a cluster of centrobin molecules that disrupt proper cell division. Patients with Mulibrey nanism lack TRIM37 and their cells show similar extra spindle poles.

Too Little and Too Much: Balanced Hippocampal, But Not Medial Prefrontal, Neural Activity Is Required for Intact Novel Object Recognition in Rats

Impaired GABAergic inhibition, so-called neural disinhibition, in the prefrontal cortex and hippocampus has been linked to cognitive deficits. The novel object recognition (NOR) task has been used widely to study cognitive deficits in rodents. However, the contribution of prefrontal cortical and hippocampal GABAergic inhibition to NOR task performance has not been established. Here, we investigated NOR task performance in male Lister hooded rats following regional neural disinhibition or functional inhibition, using intracerebral microinfusion of the GABAA receptor antagonist picrotoxin or agonist muscimol, respectively. Our infusion targets were the medial prefrontal cortex (mPFC), dorsal hippocampus (DH), and ventral hippocampus (VH).

Is bioluminescence the key to safe, effective brain imaging?

A decade ago, a group of scientists had the literally brilliant idea to use bioluminescent light to visualize brain activity.

“We started thinking: ‘What if we could light up the brain from the inside?’” said Christopher Moore, a professor of brain science at Brown University. “Shining light on the brain is used to measure activity — usually through a process called fluorescence — or to drive activity in cells to test what role they play. But shooting lasers at the brain has down sides when it comes to experiments, often requiring fancy hardware and a lower rate of success. We figured we could use bioluminescence instead.”

With a major grant from the National Science Foundation, the Bioluminescence Hub at Brown’s Carney Institute for Brain Science launched in 2017 based on collaborations between Moore (associate director of the Carney Institute), Diane Lipscombe (the institute’s director), Ute Hochgeschwender (at Central Michigan University) and Nathan Shaner (at the University of California San Diego).

The scientists’ goal was to develop and disseminate neuroscience tools based on giving nervous system cells the ability to make and respond to light.

In a study published in Nature Methods, the team described a bioluminescence tool it recently developed. Called the Ca2+ BioLuminescence Activity Monitor — or “CaBLAM,” for short — the tool captures single-cell and subcellular activity at high speeds and works well in mice and zebrafish, allowing multi-hour recordings and removing the need for external light.

More said that Shaner, an associate professor in neuroscience and in pharmacology at U.C. San Diego, led the development of the molecular device that became CaBLAM: “CaBLAM is a really amazing molecule that Nathan created,” Moore said. “It lives up to its name.”

Measuring ongoing activity of living brain cells is essential to understanding the functions of biological organisms, Moore said. The most common current approach uses imaging with fluorescence-based genetically encoded calcium-ion indicators.

Continue reading “Is bioluminescence the key to safe, effective brain imaging?” | >

Zap-and-freeze’ technique used to watch human brain cell communication

For the new study, the researchers used samples from the brains of normal mice as well as living cortical brain tissue sampled with permission from six individuals undergoing surgical treatment for epilepsy. The surgical procedures were medically necessary to remove lesions from the brain’s hippocampus.

The researchers first validated the zap-and-freeze approach by observing calcium signaling, a process that triggers neurons to release neurotransmitters in living mouse brain tissues.

Next, the scientists stimulated neurons in mouse brain tissue with the zap-and-freeze approach and observed where synaptic vesicles fuse with brain cell membranes and then release chemicals called neurotransmitters that reach other brain cells. The scientists then observed how mouse brain cells recycle synaptic vesicles after they are used for neuronal communication, a process known as endocytosis that allows material to be taken up by neurons.

The researchers then applied the zap-and-freeze technique to brain tissue samples from people with epilepsy, and observed the same synaptic vesicle recycling pathway operating in human neurons.

In both mouse and human brain samples, the protein Dynamin1xA, which is essential for ultrafast synaptic membrane recycling, was present where endocytosis is thought to occur on the membrane of the synapse.

“Our findings indicate that the molecular mechanism of ultrafast endocytosis is conserved between mice and human brain tissues,” the author says, suggesting that the investigations in these models are valuable for understanding human biology.

Continue reading “Zap-and-freeze’ technique used to watch human brain cell communication” | >

Platelet-inspired nanoparticles can boost brain-computer interface electrode performance

Scientists working to enhance brain-computer interface (BCI) technology—which allows people to control devices with their thoughts—have found they can improve the performance of electrodes implanted in the brain by targeted delivery of anti-inflammatory drugs.

/* */