User:Skcirdnehat/sandbox

http://research.mssm.edu/cnic/pdfs/golding01_spruston_APdichotomy.pdf

http://www.jneurosci.org/content/20/4/1307.full.pdf

http://www.ncbi.nlm.nih.gov/pubmed/11160533

http://www.sciencemag.org/content/305/5683/482.full?sid=e09c14f9-4131-42c2-a345-2410c39ff75a

Multiple modes of a-type potassium current regulation. Cai SQ1, Li W, Sesti F.

Diversity and Dynamics of Dendritic Signaling Michael Hausser,^* Nelson Spruston,^ Creg J. Stuart^

K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons Dax A. Hoffman, Jeffrey C. Magee*, Costa M. Colbert & Daniel Johnston

Epileptic Neurons Go Wireless (Staley)

On the biophysics group I signed up to give feedback for your review paper, but I'm pretty swamped this week so I look next week and if you have some of the body of the review paper posted then I'll be happy to give some comments and see if I can help. Jhenstro (talk) 05:07, 5 November 2015 (UTC)

I'm signed up to review your paper, it would be great if you could upload it! Rincrate (talk) 03:10, 11 November 2015 (UTC)

Hey guys, sorry, I've been quite backed up the past few weeks... I will get my stuff up later tonight. Thanks for your patience. 71.61.210.145 (talk) 09:29, 12 November 2015 (UTC)

So I added a new section to my page that talks about the regulation and inhibition and I greatly updated the mechanism section. Here is what I have (see below). Any suggestions are appreciated and once again I apologize for taking so long to get it here. Skcirdnehat (talk) 12:26, 16 November 2015 (UTC)

Mechanism[edit]

When a neuron fires an action potential, it is initiated at the axon initial segment. An action potential spreads down the axon because of the gating properties of voltage-gated sodium channels and voltage-gated potassium channels. Initially, it was thought that an action potential could only travel down the axon in one direction towards the axon terminal where it ultimately signaled the release of neurotransmitters. However, recent research has provided evidence for the existence of backwards propagating action potentials.

Neural backpropagation can occur in one of two ways. First, during the initiation of an axonal action potential, the cell body, or soma, can become depolarized as well. This depolarization can spread through the cell body towards the dendritic tree where there are voltage-gated calcium channels. The depolarization of these voltage-gated calcium channels can then result in the propagation of a dendritic action potential. Such backpropagation is sometimes referred to as an echo of the forward propagating action potential (staley). Additionally, it has also been shown that an action potential initiated in the axon can create a retrograde signal that travels in the opposite direction (Hausser). This impulse travels up the axon eventually causing the cell body to become depolarized, thus triggering the dendritic voltage-gated calcium channels. As described in the first process, the triggering of dendritic voltage-gated calcium channels leads to the propagation of a dendritic action potential.

Generally, EPSPs from synaptic activation are not large enough to activate the dendritic voltage-gated calcium channels (usually on the order of a couple milliamperes each) so backpropagation is typically believed to happen only when the cell is activated to fire an action potential. It is important to note that the strength of backpropagating action potentials varies greatly between different neuronal types (hausser). Some types of neuronal cells show little to no decrease in the amplitude of action potentials as they invade and travel through the dendritic tree while other neuronal cell types, such as cerebellar Purkinje neurons, exhibit very little action potential backpropagation. Additionally, there are other neuronal cell types that manifest varying degrees of amplitude decrement during backpropagation. It is thought that this is due to the fact that each neuronal cell type contains varying numbers of the voltage-gated channels required to propagate a dendritic action potential.

Regulation and Inhibition[edit]

Generally, synaptic signals that are received by the dendrite are combined in the soma in order to generate an action potential that is then transmitted down the axon toward the next synaptic contact. Thus, the backpropagation of action potentials poses a threat to initiate an uncontrolled positive-feedback loop between the soma and the dendrites. For example, as an action potential was triggered, its dendritic echo could enter the dendrite and potentially trigger a second action potential. If left unchecked, an endless cycle of action potentials triggered by their own echo would be created. In order to prevent such a cycle, most neurons have a relatively high density of A-type K+ channels.

A-type K+ channels belong to the superfamily of voltage-gated potassium channels and are transmembrane channels that help maintain the cell’s membrane potential (Cai). Typically, they play a crucial role in returning the cell to its resting membrane following an action potential by allowing an inhibitory current of K+ ions to quickly flow into the neuron. The presence of these channels in such high density in the dendrites explains their inability to initiate an action potential, even during synaptic input. Additionally, the presence of these channels provides a mechanism by which the neuron can suppress and regulate the backpropagation of action potentials through the dendrite. Results have indicated a linear increase in the density of A-type channels with increasing distance into the dendrite away from the soma. The increase in the density of A-type channels results in a dampening of the backpropagating action potential as it travels into the dendrite (hoffman). Essentially, inhibition occurs because the A-type channels facilitate the influx of K+ ions in order to the help main the membrane potential below threshold levels (cai). Such inhibition limits EPSP and protects the neuron from entering a never-ending positive-positive feedback loop between the soma and the dendrites.

what you added looks really good. I know dr. woodbury just said that the whole paper has to be 4-6 pages and I feel like this is more in the 3 page range, so aside from a few minor grammatical edits I also think that you could expand the article in the direction of discussing some of the bad effects of neuronal back propagation (besides the positive feedback loop) and giving specific examples of the exceptions (such as examples of extreme amplitude decrements or examples of what happens if you have too many K+ A-Type channels). Jhenstro (talk) 16:46, 17 November 2015 (UTC)

I thought the introduction is great. There was enough background to help me follow along. It would be great if you could provide examples in the body where back propagation happens or even drugs that could initiate it. Just as Jhenstro suggested, it would also be great if you could include examples of what happens with too many or not eough K+ A-type channels. Other than that, it looks great!!!! Rincrate (talk) 03:10, 19 November 2015 (UTC)