Introducing the brain: neuron comlplexity (Introduction)

by David Turell , Tuesday, September 26, 2023, 22:05 (422 days ago) @ David Turell

With long axons and dendrites there is constant biochemical activity:

read://https_www.the-scientist.com/?url=https%3A%2F%2Fwww.the-scientist.com%2Ffeatures%...

"Unlike most cells, neurons expand beyond their spherical cell bodies into a complex labyrinth of protrusions that evoke visions of naked trees in winter. Axons and dendrites sprout from the cell body, branching out in different directions in search of connections. Dendritic branches are densely populated with even smaller budding protrusions called spines, which make synapses with other neurons to receive important messages. Researchers have demonstrated how, at its most basic level, memory is modulated by strengthening weakening synaptic connections.

"A single neuron can receive messages through several thousand independent synapses spread across the dendritic arbor. “We estimate that around 80% of the volume of a neuron is not in the cell body but rather in the dendrites and the axons,” said Schuman.

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"...She was curious if brain-derived neurotrophic factor (BDNF), a chemical messenger she knew to be important for the growth and survival of developing neurons, also had a functional role in mature neurons. To her surprise, BDNF dramatically increased synaptic activity for hours, similar to what was seen with LTP [long-term potentiation], but activity was completely blocked when she bathed the slices in a protein synthesis inhibitor.7 Unlike LTP, BDNF-induced activity required immediate access to new proteins.

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"When she bathed the disconnected dendrites in BDNF, they still exhibited synaptic plasticity, and therefore immediate protein synthesis, despite being physically separated from the protein factories.8 Rather than making use of premade proteins until reinforcements arrive, as was suggested with LTP, these findings suggested that synapses could produce their own proteins on demand.

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"...The work of Schuman and others highlighted how neurons could synthesize proteins locally, but many questions regarding the specificity and underlying mechanisms remained.

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"...A tsunami of evidence in the late 1990s and early 2000s made it clear that neurons could engage in local translation, but it was still unclear how neurons achieved such speed and precision.

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"compared to other cells, neurons pose a unique challenge to cell biology. With thousands of independently modified synapses, RNA localization and translation must be precise to maintain synaptic specificity while avoiding mislocalization or improper protein production. “In the neuron where you have such huge distances, I think the neuron has evolved a more elaborate model,” said Robert Singer, a cell biologist at Albert Einstein College of Medicine. (my bold)

"Local translation makes sense from a logistics point of view. A single mRNA transcript can produce numerous protein copies, labor that the cell body can outsource too far away regions in the neuron. Furthermore, with protein building materials nearby, far away synapses can rapidly respond to incoming information and infrastructure demands without waiting for the cell body to complete their supplies order.

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"Moving down the assembly line, components needed for translation, including mRNA, ribosomes, and regulatory proteins, get packed and loaded into RNA transport granules.12 These transport granules orchestrate the spatiotemporal transport and translation of mRNA and protect the transcripts from degradation.

"Delivery of the RNA granules is powered by motor proteins that move these packages along the neuron’s vast microtubule and actin cytoskeleton road network to reach far away compartments.

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"...they used a technique called Ribo-seq to capture and sequence mRNA that are actively undergoing translation.19 While most proteins are synthesized in both the cell body and distal compartments, they found around 800 mRNA transcripts that exhibited more translation in axons and dendrites, suggesting that local translation contributes significantly to the local proteome. “This was another surprise for us because the thinking was that most of the mRNA are still primarily translated in the cell body, but actually, for a huge number of mRNA, their primary source of synthesis is local,” said Schuman.

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"Translational control drives many processes, including neuronal development, learning and memory, and axonal repair. To manage local translation across huge distances, the neuron has evolved an elaborate model with specialized packages and sophisticated road networks." (my bold)

Comment: a long historical review. The neuron is like no other cell, but like a city phone system. It had to be designed, not by chance, since brains first appeared de novo in the Cambrian explosion.