Lifeboat Foundation

Electrical activity in neurons is highly energy demanding and accompanied by rises in cytosolic Ca²⁺. Cytosolic Ca²⁺, in turn, secures energy supply by pushing mitochondrial metabolism either through augmented NADH transfer into mitochondria via the malate aspartate shuttle (MAS) or via direct activation of dehydrogenases of the TCA cycle after passing into the matrix through the mitochondrial Ca²⁺ uniporter (MCU). Another Ca²⁺-sensitive booster of mitochondrial ATP synthesis is the glycerol-3-phosphate shuttle (G3PS) whose role in neuronal energy supply has remained elusive. Essential components of G3PS are expressed in hippocampal neurons. Single neuron metabolic measurements in primary hippocampal cultures derived from rat pups of either sex reveal only moderate, if any, constitutive activity of G3PS. However, during electrical activity neurons fully rely on G3PS when MAS and MCU are unavailable. Under these conditions, G3PS is required for appropriate action potential firing. Accordingly, G3PS safeguards metabolic flexibility of neurons to cope with energy demands of electrical signaling.

SIGNIFICANCE STATEMENT:

Ca²⁺ ions are known to provide a link between the energy-demanding electrical activity and an adequate ATP supply in neurons. To do so, Ca²⁺ acts both, from outside and inside of the mitochondrial inner membrane. Neuronal function critically depend on this regulation and its defects are often found in various neurological disorders. Although interest in neuronal metabolism increases, many aspects thereof have remained unresolved. In particular, a Ca²⁺-sensitive NADH shuttling system, the glycerol-3-phosphate shuttle, has been largely ignored with respect to its function in neurons. Our results demonstrate that this shuttle is functional in hippocampal neurons and safeguards ATP supply and appropriate action potential firing when malate aspartate shuttle and mitochondrial Ca²⁺ uniporter are unavailable, thereby ensuring neuronal metabolic flexibility.

Lecture from the mini-series “Cosmology & Quantum Foundations” from the “Philosophy of Cosmology” project. A University of Oxford and Cambridge Collaboration.

This session explores the nature of consciousness, including efforts to define and measure it. What systems have subjective experience? What do we mean when we refer to various types of consciousness? How simple, and how sophisticated, can consciousness in principle be? Can we define necessary conditions for a physical system to be conscious? Sufficient conditions?

David Chalmers at FQXi’s 5th International Conference.

Summary: A new language-switching experiment revealed traditional categorization of brain areas may not be sufficient. Researchers set their sights on the caudal inferior parietal cortex to better understand functional categorization in the brain.

Source: Leiden University.

Based on the results of a language-switching experiment, Ph.D. candidate Fatemeh (Simeen) Tabassi Mofrad MA and Professor Niels Schiller have discovered that the traditional categorization of brain areas is not sufficient.

The trial was only on 8 people, but it appears to have worked well across the board.

Published in GeroScience, a groundbreaking study from the renowned Conboy lab has confirmed that plasma dilution leads to systemic rejuvenation against multiple proteomic aspects of aging in human beings.

This paper takes the view that much of aging is driven by systemic molecular excess. Signaling molecules, antibodies, and toxins, which gradually accumulate out of control, cause cells to exhibit the gene expression that characterizes older cells.

Continue reading “Plasma Dilution Appears to Rejuvenate Humans” »

For trained mathematical brains, the infinite is if anything even more bamboozling. Mathematicians have known for well over a century now that infinity isn’t just one thing, it is infinitely many. There is an unending tower of ever greater infinities stretching up all the way to… well, whatever you’d like to call it.

That isn’t even the worst of it. Although the existence of this tower of infinities is a logical consequence of mathematics as we know it, that same mathematics is powerless to describe it completely. Chip away at the plaster to reveal the structure underneath and you see that crucial load-bearing beams are missing in the lower levels, suggesting that the foundations of mathematics itself are unstable.

Mathematicians have long argued about how best to shore the infinite tower up. Some say we should simply leave well alone and hope for the best. Others have proposed fixes, variously deemed too costly, unlikely to work or not in keeping with the original style. No one has yet made anything like a breakthrough. Except, perhaps, until now. After decades of apparent stalemate, serious progress seems to have been made on the baffling question that lies at the heart of it all: a nearly 150-year-old unproven conjecture known as the continuum hypothesis.

In a study published in Cell Reports, we present a novel algorithm for the digital generation of neuronal morphologies, based on the topology of their branching structure. This algorithm generates neurons that are statistically similar to the biological neurons, in terms of morphological properties, electrical responses and the connectivity of the networks they form.

This study represents a major milestone for the Blue Brain Project and for the future of computational neuroscience. The topological neuron synthesis enables the generation of millions of unique neuronal shapes from different cell types. This process will allow us to reconstruct brain regions with detailed and unique neuronal morphologies at each cell position.

The topological representation of neurons facilitates the generation of neurons that approximate morphologies that are structurally altered compared to healthy neuronal morphologies. These structural alterations of neurons are disrupting the brain systems and are contributing factors to brain diseases. The topological synthesis can be used to study the differences between healthy and diseased states of different brain regions and specifically, what structural alterations of neurons are causing important problems to the networks they form.

Scientists have discovered that increasing the production of new neurons in mice with Alzheimer’s.

Alzheimer’s disease is a disease that attacks the brain, causing a decline in mental ability that worsens over time. It is the most common form of dementia and accounts for 60 to 80 percent of dementia cases. There is no current cure for Alzheimer’s disease, but there are medications that can help ease the symptoms.