Why is neuronal repolarization during #ActionPotentials so uniform despite ~10x range in axonal diameter? Study shows that higher K+ currents in smaller #axons compensate for biophys constraints, resulting in size-independent trigger signals #PLOSBiology https://plos.io/3ZzJvzE
#axons
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A major criticism is that the technique of high-pressure freezing only handles very small volumes at most 200 micrometers thick, and therefore, the tissue being from a mouse brain, a significant amount of injury to neuronal arbours was caused to generate such small samples.
Three kinds of samples were used:
(1) Cell culture neurons, which have their own problems and can't be considered authoritative on neuronal morphology.
(2) Hippocampal slices, which do recover from sectioning when in the right culture medium but only to some extent. Most neurons exist as fragments in the slice. Artifacts in morphologies are expected.
(3) Acutely extracted brain bits can't be immediately frozen; even a second is enough for neurons to fire and osmolarity to shape neuronal morphologies away from the natural state.
In summary: while surely neurons in their natural state don't look like those in textbooks, since all sample preparations suffer from artifacts, I am not convinced that this study resolves the issue. Try to freeze a small animal – like it's been done for C. elegans. Do these peculiar axon morphologies exist in the HFP'ed worm?
The authors themselves admit that:
"treatments that disrupt these parameters like hyper- or hypo-tonic solutions, cholesterol removal, and non-muscle myosin II inhibition all alter the degree of axon pearling" – and all of these come into play during sample preparation.
Preprint: https://www.biorxiv.org/content/10.1101/2023.07.20.549958v1.full
As published: https://www.nature.com/articles/s41593-024-01813-1
I wish the reviews were published. Andreas Prokop, a neuroscientist working on microtubules in neurons, was involved, which is reassuring.
bioRxiv · Membrane mechanics dictate axonal morphology and functionAxons are thought to be ultrathin membrane cables of a relatively uniform diameter, designed to conduct electrical signals, or action potentials. Here, we demonstrate that unmyelinated axons are not simple cylindrical tubes. Rather, axons have nanoscopic boutons repeatedly along their length interspersed with a thin cable with a diameter of ∼60 nm like pearls-on-a-string. These boutons are only ∼200 nm in diameter and do not have synaptic contacts or a cluster of synaptic vesicles, hence non-synaptic. Our in silico modeling suggests that axon pearling can be explained by the mechanical properties of the membrane including the bending modulus and tension. Consistent with modeling predictions, treatments that disrupt these parameters like hyper- or hypo-tonic solutions, cholesterol removal, and non-muscle myosin II inhibition all alter the degree of axon pearling, suggesting that axon morphology is indeed determined by the membrane mechanics. Intriguingly, neuronal activity modulates the cholesterol level of plasma membrane, leading to shrinkage of axon pearls. Consequently, the conduction velocity of action potentials becomes slower. These data reveal that biophysical forces dictate axon morphology and function and that modulation of membrane mechanics likely underlies plasticity of unmyelinated axons.
### Competing Interest Statement
The authors have declared no competing interest.
#Nerve #cells (#neurons ) are amongst the most complex cell types in our body. They achieve this complexity during development by extending ramified branches called #dendrites and #axons and establishing thousands of synapses to form intricate networks.
#Neuroscience #sflorg
https://www.sflorg.com/2024/04/ns04082401.html
www.sflorg.comFueling nerve cell function and plasticityHow mitochondria control tissue rejuvenation and synaptic plasticity in the adult mouse brain
"We show that migrating #neurons in mice possess a growth cone at the tip of their leading process, similar to that of #axons, in terms of the #cytoskeletal dynamics and functional responsivity through protein tyrosine #phosphatase receptor type sigma (PTPσ). Migrating-neuron growth cones respond to chondroitin sulfate (CS) through PTPσ and collapse, which leads to inhibition of #neuronal migration."
NatureIdentification of the growth cone as a probe and driver of neuronal migration in the injured brain - Nature CommunicationsStructure and functions of the tip of migratory neurons remain elusive. Here, the authors show that the PTPσ-expressing growth cone senses extracellular matrix changes and drives neuronal migration in the injured brain, leading to the functional recovery.
Hacker News Short-term Hebbian learning can implement transformer-like attention
https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1011843
#ycombinator #Action_potentials #Neuronal_dendrites #Axons #Neurons #Synapses #Machine_learning #Calcium_channels #Ion_channels
journals.plos.orgShort-term Hebbian learning can implement transformer-like attentionAuthor summary Many of the most impressive recent advances in machine learning, from generating images from text to human-like chatbots, are based on a neural network architecture known as the transformer. Transformers are built from so-called attention layers which perform large numbers of comparisons between the vector outputs of the previous layers, allowing information to flow through the network in a more dynamic way than previous designs. This large number of comparisons is computationally expensive and has no known analogue in the brain. Here, we show that a variation on a learning mechanism familiar in neuroscience, Hebbian learning, can implement a transformer-like attention computation if the synaptic weight changes are large and rapidly induced. We call our method the match-and-control principle and it proposes that when presynaptic and postsynaptic spike trains match up, small groups of synapses can be transiently potentiated allowing a few presynaptic axons to control the activity of a neuron. To demonstrate the principle, we build a model of a pyramidal neuron and use it to illustrate the power and limitations of the idea.
`#Oligodendrocytes (from Greek 'cells with a few branches'), also known as oligodendroglia, are a type of #neuroglia whose main functions are to provide support and insulation to #axons within the central nervous system (CNS) of jawed vertebrates. Their function is similar to that of Schwann cells, which perform the same task in the peripheral nervous system`
en.wikipedia.orgOligodendrocyte - Wikipedia
#introduction. I am a neuro/cell/dev biologist investigating how the delicate meter-long slender processes of neurons, i.e. the #axons that form the cables wiring our nervous system, can be maintained for a century (or fail in neurodegeneration). As an efficient strategy, I use genetics and neurons of the fruitfly #Drosophila able to deal with the enormous complexity at play (image). For many years I have engaged in #scicomm promoting the importance of fly research (https://poppi62.wordpress.com/publications/)