What factors influence the differentiation of neurons?

[daniel350]

Of late, I have been self-learning about the underlying biology behind neurons; saltatory conduction; electrotonic and action potentials. I have (at least for the most part) surmised a basic understanding of how most of this works.

What I don't understand, is how do the neurons differentiate? How is any information 'stored'?

From what I have learned up to this point, the only differentiation in a network of neurons is the:

• Number of synapses (connections) between the neurons
• and therefore the differences in attenuation for the electrotonic potential as it moves to the Axon hillock.
• The neurotransmitters released in synapses.

If not for the connections changes (dendritic spines), there does not appear to be an inherent value that changes in the neuron?

Also, how are the neurotransmitters in each synapse different.
What decides that synapse A will have x amount of GABA, and synapse B have y amount of Glutamate.

How does a dendritic spine form if it does not exist in the first place? Is it like a chance bonding between a dendrite and axon terminal based on distance? Obviously (?) its growth or demise is based on the frequency of firing.

 

[Ryan_m_b]

I'm not entirely sure what you mean by "differentiate" as this has to do with cells changing their phenotype into other cells. Do you mean how they differ?

To answer your other questions;

- Neurotransmitters differ because they are different chemicals
- Dendritic spines form from filopodia (outgrowths) during synaptogenesis. If I remember correctly some of these filopodia will create synapses and then form dendritic spines.

 

[daniel350]

I was referring to the English definition of the word: "a discrimination between things as different and distinct;", so "differ" would be fine too.

I extended my question a bit, I meant in terms of each synapse, why do the neurotransmitters stored for release change between synapses, ie synapse A will have x amount of GABA, but synapse B will only have y amount. What determines this?

Thanks for pointing me towards synaptogenesis, that helped a lot in terms of initial dendritic spine formation. Although how they reform is still a bit of a mystery.

Also, the size/strength of a dendritic spines is relational to the firing frequency of its synapse'. What effect does this have on the electrotonic potential?

 

[Pythagorean]

A bigger dendrite generally has a shorter electronic length (that is, signals attenuates less).

Both the environment and genetic dispositions can shape synaptic strength in a variety of ways.

 

[daniel350]

So am I to assume due to the relatively speculative nature of most of these answers, and most out there on the net. Theres still a lot of research to be done?

 

[Pythagorean]

Fair enough:

Comparative Electrotonic Analysis of Three Classes of
Rat Hippocampal Neurons
Nicholas T. Carnevale, Kenneth Y. Tsai, Brenda J. Claiborne and Thomas H. Brown
J Neurophysiol 78:703-720, 1997.

The Morphoelectrotonic Transform: A Graphical Approach to Dendritic Function
Anthony M. Zador,’ Hagai Agmon-Snir,2 and ldan Segev2
‘Salk Institute, San Diego, California 92037, and 2Department of Neurobiology and Center for Neural Computation, Institute of Life Sciences, Hebrew University, Jerusalem, Israel

If you want a deeper answer for:

I extended my question a bit, I meant in terms of each synapse, why do the neurotransmitters stored for release change between synapses, ie synapse A will have x amount of GABA, but synapse B will only have y amount. What determines this?

You have to realize that there's a lot of factors (both environmental and genetic). It's not particularly speculative that they are factors, but you might argue that it's speculative how the factors combine and which ones dominate in particular situations.

The presynaptic membrane has it's own receptors on it that detect neurotransmitter and can initiate a reaction to inhibit release, so there is one mechanism for how much neurotransmitter is released. Each neuron's receptor amount and sensitivity is set by a series of chain reactions between proteins and the genome and the stimulus. For instance, one neuron may send continuous strong signals to another neuron, so the receiving neuron will adjust by reducing the receptor count or sensitivity. This is an example of "desensitization" or "habituation".

 

[Ygggdrasil]

You may want to read up on the topic of synaptic plasticity: the ways in which the strength of a synapse between two neurons can change over time (over both short and long periods of time). I don't know a lot about this area, but in response to frequent/infrequent firing at a specific synapse, different cellular signaling pathways can get activated that do thing like modify the proteins at the synapse to alter their activities, and change the genes being expressed by the cell. These event can lead to changes in both the presynaptic and postsynaptic cells that can lead to weakening/strengthening the connection between the two neurons.

But I would agree that the basic question of how synaptic connections change over time is still a very active area of research that we don't understand very well yet.

 

[daniel350]

Thanks for the answers guys, any further answers will also be appreciated, but I think I'll have to start digging into some research papers, as Pythagorean has listed.

Been very helpful so far :).

edit: For others that are interested, there's some good papers on http://jn.physiology.org/

 

[atyy]

Many factors are involved.

Molecules:
http://www.jneurosci.org/content/30/15/5334.abstract

Electrical activity:
http://www.jneurosci.org/content/27/6/1271.abstract

Sensory experience:
http://www.jneurosci.org/content/26/16/4155.abstract