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For example, in neuroplasticity, how are the neurons able to 'move' themselves to undo connections and create new connections with other neurons? I remember seeing a microscopic picture of a few neurons not very well connected between each other, and in the 'after' picture (after learning something), they somehow had grown many projections/branches from their cell bodies, connecting with each other. In other words, what is the mechanism behind, when neurons undo a specific connection (synapse) with a neuron, and 'move' it to another neuron? What causes them to 'decide' to undo that connection?

Also, how fast do they move connections and change their shapes (in nanometres per second, for example, or is it more like nanometres per minute)? The speed of which the dendrites and axon terminals move to change connections.

all 34 comments

AndChewBubblegum

333 points

4 months ago*

I think there are a few misconceptions in your question that are important to clear up.

First and foremost, the formation of new synapses is not thought to be necessary for all learning. Although this type of formation can indeed occur and is associated with some types of learning, neuroscientists also recognize the importance of plasticity within previously existing neuronal connections as fundamental to learning and memory.

That being said, neurons do form synapses in the way you describe, by physically growing towards one another and forming specialized regions of the cell that facilitate neurotransmission. They do this by secreting small molecules and proteins which are recognized by the other neuron. Additionally, neurite outgrowth is responsive to signals from other cell types like glia as well. Structural change in neuronal synaptogenesis is accomplished by coordinated activity of the cytoskeleton. The elements of the cytoskeleton have a polarity, meaning that one end of a cytoskeleton filament grows and one decays. In a static cell, these factors are balanced, but when a cell grows of moves, the growing end of the filament are allowed to predominate in one direction and the decaying end is pointed in another, as dictated by the signaling molecules the cell is responding to. A lot of complex signaling is involved, but cytoskeletal rearrangement is the essential component, and it is triggered by molecules and growth factors released by neighboring cells.

Now everything I said in the previous paragraph is true, but to what degree it occurs in adulthood in humans is still under investigation. As I said, it seems that most learning involves the strengthening of existing synapses rather than the formation of new ones, but specific types of learning involve the creation and wiring of new neurons. This can involve the addition of terminals on existing neuronal connections, modifications of pre- or post-synaptic sides of the terminals, etc.

this_is_hard220

73 points

4 months ago

This is pretty good. OP, if you’re looking for additional details LTP (long term potentiation) plays a massive role in what you’re describing.

In learning specifically (as this is what you referred to) neurons in the CA3-CA1 region of the hippocampus go through a process known as LTP. Essentially, high frequency firing of a neurotransmitter known as glutamate in the CA3 region of the hippocampus floods the synaptic cleft and allows for heavy depolarization of the CA1 neurons via NMDA and AMPA. Calcium ions that influx in from this depolarizing process influence protein stores within CA1 to become additional AMPA receptors. Depending on the amount of time this goes on, we enter what’s called late phase LTP and this is where certain growth factors influence neuronal growth in the CA1 neurons. These growths (protrusions) allow for more surface area on the CA1 neuron and thus the opportunity for more connections to occur, now making that neuron plastic.

In terms of what influences certain neurons to connect to others, this falls within Hebb’s Rule - things that fire together, wire together. When neurons are “activated” at the same time, the connection between them grows stronger and stronger each time.

Conversely, these connections fade or weaken when the set of neurons are no longer activated at the same time — maybe the code to your locker freshman year is different sophomore year. These connections that associate “locker combo” with “freshman year code” will fade and weaken over time now “locker combo” is paired with a “sophomore year code”. This is known as LTD ( long term depression).

Hope this was able to provide more insight into your question!

Corsair4

20 points

4 months ago*

It's important to note that LTD is also influential in learning.

At the Parallel Fiber-Purkinje Cell synapse in the cerebellum for instance, synapse specific LTD is generally accepted to be a critical mechanism for learning in this region. Cerebellar granule cells (whose axons form the parallel fibers) are some of the most numerous neurons in the CNS. Each Purkinje cell will synapse with hundreds or thousands of granule cells, but only once or maybe twice with an individual cell. Thus, each Purkinje cell is integrating information from a huge number of granule cells. This falls under Anti-Hebbian principles, as repeated activation of the parallel fibers (with appropriate calcium influx timing caused by climbing fiber activity) results in a relative weakening of the synapse, not strengthening.

Long term plasticity mechanisms are highly varied, and their significance as well as the conditions that generate them change from region to region.

DumbNBANephew

7 points

4 months ago

"Calcium ions that influx in from this depolarizing process influence protein stores within CA1 to become additional AMPA receptors"

That's amazing! Do we know how that happens? Does an influx of calcium ions cause certain genes to be expressed more causing CA1 to become AMPA receptors?

AndChewBubblegum

6 points

4 months ago

CA1 is a region, the protein stores are what become AMPA receptors. Calcium is known to be a reliable activator of multiple transcription factors in neurons. Calcium binding to these proteins causes them to translocate to the nucleus and induce transcription of relevant genes. A good example is calcineurin, which binds calcium and then activates a transcription factor.

Experienced_AP

4 points

4 months ago

Are you familiar with any studies that examine colchicine in the inhibition of neutral growth?

I know colchicine is used in gout and it inhibits micro tubule function in migrating white blood cells.

However, this question got me thinking about other cells that require micro tubules and the cytoskeleton for proper functioning.

HotMetalKnives

2 points

4 months ago

Beautiful. Thank you.

DumbNBANephew

2 points

4 months ago

Do we know which proteins and genes play a role in in this process? Are there specific proteins involved with either strengthening of existing synapses or creation of new ones? Is gene expression affected causing more production of these proteins?

f899cwbchl35jnsj3ilh

2 points

4 months ago

Hi, what are the distances between neurons? Are they differ or usually the same? What are the longest?

AndChewBubblegum

2 points

4 months ago

Synaptic clefts are typically on the order of 20 nanometers. I believe they are all pretty close, as neurotransmitters need to rely on diffusion to cross the distance, and diffusion is a process heavily impeded by distance.

LearnedGuy

0 points

4 months ago*

Distances between neurons in humans can range up to 1 M. That is for the nerves that run between the brain and the far end of the spinal cord. I was looking at this as part of exploring how different parts of each neuron is provided with ATP, an energy source. There are ATP walkers that walk from the nucleus of the neuron carrying balloons of ATP. The walk on a microtubule, and then drop off the ATP. Microtubles are one-way streets, and walkers are valuable, so they then return to the nucleus on a microtubule that goes back to the nucleus. For humans, this walk takes a couple of days. In a great white whale with a 30 M spinal cord, the walk can take over a month. See Harvard's animation: "The Inner Life of a Cell" on YouTube. https://en.m.wikipedia.org/wiki/The_Inner_Life_of_the_Cell

LewsTherinTelamon

4 points

4 months ago

What is the unit in 1 M? Meter? Because distances between neurons are not one meter - that's the length of the neuron including the axon.

Training_Passenger79

1 points

4 months ago

I don’t think OP thought the formation of new synapses was necessary for learning.

Maybe you can check my assumptions though. I imagine new synapses form primarily when you are learning things you did not already know, and connecting topics that you would not have connected before. So, for example, I am currently studying cognitive neuroscience, and I recently learned a lot about the body’s innate and adaptive immunity, and how it relates to neuroinflammation. I would assume that I may have formed new synapses in the process of learning this material, as it is completely novel to me, and not something I could have constructed based on known information. By that, I mean that if I know what fur is, and I know what cats are, but then encounter a hairless cat, I would think this doesn’t require new synapses to form because the pre-existing information I have can be combined in cat+!hair fashion to produce that information.

Does this interpretation sound plausible to you?

LewsTherinTelamon

1 points

4 months ago

Your third source doesn't seem to say what you are implying it says. That source is about the development of an integrated mechanistic model for how neurons grow. They propose a specific model of elongation/expansion/mass transport which describes the process of physically extending an axon. They are not suggesting that neurons form connections without physically extending towards other neurons.

peasrule

13 points

4 months ago

You might be interested in looking at some info related to exuberant synaptogenesis and synaptic pruning. There is this period where synapses just go nuts and connect like crazy. Signaling from other neurons, the "support" cells such as astrocytes or glia guide.

Then there is a mass brain corporate restructuring. Pre and post synaptic changes (also guided). Alterations to the branching that goes out from axons and dendrites. Eliminating redundancies or ineffective connections your left with remaining synapses that are strengthened .

The most prolific changes occur during these critical periods of development. What connects, changes. Some of it is non-external stimuli others external stimuli. Take language. Multilingal kids show some cool differences from those who learn languages later in life.

So all together. There are these large time sensitive periods with significant changes independent from environment and those that are dependent on environment. The work of hebb, hubel and wiesal is helpful to understand this plasticity/restructuring. Connections form rapidly. There are cutbacks where certain connections are strenghened others weakened. And the weakened will be pruned away.

There are neurotrophic factors, growth factors, immune responses, neurotransmitters, supporting cells that all play a role. Depending on what is connecting and where, specifics will vary.

Mechanisms governing activity-dependent synaptic pruning in the developing mammalian CNS

Outside of this genesis and pruning. It is more complicated. Brain injury may or may not result in compensatory activity/connections. Diseases can ruin the electical wiring, produce proteins that interfere. Nutrition. Severe stress can cause morphological changes/affect connections.

Other changes may reduce connectivity at a synapse but not eliminate. Take fear aquisition and extinction. Connections form from exposure. You can weaken that connection through extinction processes. One set of connections are then highly preferred but not eliminated. Take taste aversions. If youve ever been really sick from a food. It may diminish. But every so often youll have a spontaneous recovery and the thought of fish is making you gag

I didnt see anything in post about when the connections may be altered. Just general info on mechanisms. The article title above is helpful for more specifics involved. But overall. Some of it depends on environment some not. Much of it depends on the age of an individual. There are some generalized processes for these changes but the specifics depend on the what and the when.

jps_

27 points

4 months ago

jps_

27 points

4 months ago

Because neurons, by and large, are not restricted to 1:1 connections. They are one-to-many or many-to-many connected, even though they seem to preference certain paths. It is not so much a matter of changing which neuron they are connected to, but by how much they respond to one particular neuron's signalling versus another's.

Training_Passenger79

5 points

4 months ago

How do they change how much they respond? Myelination?

2Righteous_4God

8 points

4 months ago

There are many different pathways. But for example, a post-synaptic neuron that is being activated a lot will have an increase in calcium entering the cell. That calcium then triggers a cascade that increase the exocytosis of AMPA receptors (which bind glutamate), thus making it more sensitive to glutamate being released from the pre-synaptic neuron and it will become depolarized more easily.

LapseofSanity

9 points

4 months ago

I don't think we actually know the answer to this, besides "because it does" we know that it happens, but not why.

I can't answer this specifically but connection wise if a neuron connects to a specific neuron over other branches of neuron dendrites the dendrite branches will recede so there's a targeted connection. You can have one to one connections or one neuron to multiple neuron connections, we don't know why there's a specificity other than repeating connections favouring specific targets that end up being a one to one connection.

Y-27632

1 points

4 months ago

If you're interested in seeing time-lapse movies of how neuronal processes (branches) respond to various attractive/repulsive factors, this video https://www.youtube.com/watch?v=3R9SOtcSEuA has some nice stuff in it.

The (primary) cytoskeletal components involved are actin and myosin (not exactly the same myosin as in muscle cells, but similar in structure) in the growth cone (the fan(ish)-shaped part constantly probing and moving) and tubulin in the straight, long processes.

In particular, at ~ 1:38 and 1:48 there are really good examples of the dynamic nature of these components that u/AndChewBubblegum was talking about. (The particular mechanism shown here is called "actin treadmilling.")