eSagan 🇮🇳 @crackurbones@qoto.org
Joined Nov 2019
🔸 The enteric nervous system is one that's shared throughout the vertebrates. And it lines the digestive track — from the esophagus through the stomach, through the small intestine, And then through the large intestine and down to the anus.
🔸 And throughout that length, there are intrinsic neurons that sit in the lining in the gastrointestinal tract. And these neurons form the enteric nervous system. And there are about 100 million.
🔸 These intrinsic neurons form two different plexuses.
🔸 One of the plexuses, called 'peristalsis', is responsible for pushing the contents of the digestive tract through the pathway from mouth to anus. The other plexuses are responsible for secreting stuff, such as making our feces either more or less watery.
🔸 The way that this enteric nervous system works is that it's very automatic. This is the most automatic of the autonomic nervous system. We're not doing anything conscious to push the food through, from esophagus to anus. That's all taken care of by the enteric nervous system (ENS).
🔸 As you may imagine, if you don't have an enteric nervous system, then food doesn't get pushed through. And that actually happens in a disease called Hirschsprung's disease.
🔸 #HirschsprungsDisease is identified at birth. So the newborn babies have Hirschsprung's because a section of the GI tract is aganglionic — it has no neurons.
And therefore, it's just contracted. And everything can push down, but it can't push through that contraction. This has to be fixed surgically. Another name for Hirschprung's is #megacolon. They got in this enlarged colon, because nothing's going through.
🔸 While the ENS is completely able to do all of this peristalsis stuff on its own, it does interact with the central nervous system. There is information going to the central nervous system — a lot of information. And there's some information coming from the CNS to the ENS. This is all coming to it through the parasympathetics and the sympathetics.
🔸 The information coming out of the enteric nervous system is about ten times more than the information that's going to the enteric nervous system. The information that comes from the digestive tract is telling us about whether we feel full, whether we just ate a large meal and our abdomen is distended, whether we feel gassy, whether we feel hungry, whether we feel good. It, it is telling us about the state of our GI tract.
🔸 The information going to the to the enteric nervous system is a way by which our mood can now influence our GI functioning.
And this is the way that if you get very nervous or excited, you may notice a difference in your bowel movements. [ so relatable for me! ]
🔸 There's an interaction between the way our digestive tract feels and the way we feel emotionally. Not surprisingly many psychiatric diseases are associated with certain GI issues as well.
Varkala Beach, Are you a mountain person or beach person? (In pic: Chamera Dam Lake, #Dalhousie, Himachal Pradesh)
https://www.reddit.com/r/IncredibleIndia/comments/fhvwau/are_you_a_mountain_person_or_beach_person_in_pic/
🔸 There's a huge class of receptors that don't form a pore and these are called metabotropic receptors.
🔸 So, metabotropic receptors, like ionotropic receptors, will bind neurotransmitters. But they do not directly lead to an electrical change because this molecule cannot form a pore. Instead, this complex is attached to a G-protein.
🔸 Once the receptor is bound to neurotransmitters, the G-proteins are activated. And they are going to go off and do things like simulating enzymatic reactions, or they're going to bind to other molecules that are in-turn going to simulate enzymatic reactions. So these G-proteins are going to go and do things, but that means it takes time.
🔸 The second thing is that what's the effect of this? Well the effect could be to open a channel, an ion channel somewhere; it could be to close an ion channel. Or it could have no effect on the ion channels. It could just go off and actually elicit a change in the genetic transcription. So it could have an electrically silent effect on the cell. So there is a huge variation in effect.
🔸 Another thing that is different about these metabotropic receptors is that they're incredibly numerous and varied. There are more than 1000 types, while there are less than 10 types of ionotropic receptors.
🔸 Not only do metabotropic receptors take time to activate for the effect to be seen, but the metabotropic receptor amplifies — it goes through many rounds of activating these G-proteins, and so it can have a lasting effect that is pretty difficult to turn off.
🔸 Many of the drugs that we use to treat Glaucoma, motion sickness, arrhythmias, hypertension, asthma, Irritable Bowel Syndrome and so on are acting on G-protein coupled receptors. So this is a very common target for drug development.
The benefits of walking away
🔴 Receptors
🔸 The next hurdle is to make sure that the postsynaptic cell receives that message. And it receives the message through a type of multi-protein complexes called receptors.
🔸 The trans-membrane protein-complexes in the cell membrane form a pore, and through this pore, the ions can travel. So, the Potassium ions can go out, the Sodium ions can come in, and Chloride ions can come in.
Normally these receptors are closed and the ions can't come in. But, when a neurotransmitter binds to the receptor, or a couple of neurotransmitter molecules bind to the receptor, the receptors open and the pore becomes available for the ions to travel along.
🔸 And which way they travel? Depends on the type of receptor. And so, as it turns out, we have two basic classes of receptors.
🔸 There are receptors that have an excitatory effect. Any receptor that takes the membrane potential closer to 0 (from -65mV) is an excitatory receptor.
🔸 On the other hand, if there is a receptor that actually takes the membrane potential away from zero, making it even more negative — thus taking it away from the threshold for the action potential — is an inhibitory receptor.
🔸 The most ubiquitous excitatory receptor is a a glutamate receptor. And the most ubiquitous inhibitory receptor is a GABA receptor.
🔸 The neurotransmitter involved that binds to the inhibitory GABA receptor is a GABA molecule. And the neurotransmitter that binds to the excitatory glutamate receptor is glutamate.
🔸 In Myasthenia Gravis, there are antibodies that the body makes by mistake against these acetylcholine receptors. And so, the antibodies destroy acetylcholine receptors. And therefore, the signal is sent from the motor neuron terminal, but it is not received by the muscle.
🔸 We know that the motor neuron terminal can release acetylcholine and we need to stop degradation of acetylcholine. We're going to give acetylcholinesterase inhibitor to try and keep the acetylcholine around longer, so that it can find it's way to the few remaining acetylcholine receptors.
🖼️ Image source: https://www.khanacademy.org/science/biology/human-biology/neuron-nervous-system/a/neurotransmitters-their-receptors
Major #Greenland glacier collapse 90 years ago linked to #climatechange https://t.co/uLTMS6foPk
https://twitter.com/physorg_com/status/1237744019012300801?s=09
#Microbes could influence your desire to get outside
https://t.co/wnIZEYUCmW
https://twitter.com/medical_xpress/status/1237744128731090944?s=09
🌱 AMAZING Small Farm in France Under TREES! // Aromath Farm
https://www.youtube.com/watch?v=HAZwj23DxVE
We May Have Finally Found a Chunk of Theia Buried Deep Inside The Moon
https://www.sciencealert.com/we-may-have-finally-found-a-chunk-of-theia-buried-deep-inside-the-moon
The Fastest Supercomputer on Earth Is Being Deployed Against Coronavirus - ExtremeTech
https://www.extremetech.com/computing/307381-the-fastest-supercomputer-on-earth-is-being-deployed-against-coronavirus
The US Department of Energy has announced that the Summit supercomputer will be used to attempt to find a treatment or cure for Covid-19.
🔸 Between two neurons lie the pre-synaptic cell and the post-synaptic cell (cells with the synaptic terminal). They are separated by a short distance called the 'synaptic cleft'.
And the molecules of nerve transmitter are going to make their way from pre-synaptic cell to post-synaptic cell through the synaptic cleft.
🔸 Neurotransmitters need to have a termination, if they are not received by the post-synaptic cell. We use three different mechanisms to terminate the message of a neurotransmitter.
1️⃣ Diffusion: The molecules are simply going to diffuse out if they don't make it to the "ears" of post-synaptic terminal of the receiving neuron. So diffusion is a very effective way to terminate a message.
2️⃣ The second way is through something called re-uptake. And re-uptake is typically in the pre-synaptic terminal. There are channels, or transporters, which take neurotransmitters back up. The neurotransmitters get re-packaged and put back into a new vesicles (which are actually recycled as well).
🔸 And this is really important for drugs like #serotonin and #dopamine. And there are drugs that act on the serotonin and dopamine re-uptake transporters that can be used both therapeutically, for instance, to treat depression.
3️⃣ The third way that we terminate a message is through degradation. And in the case of degradation, what we have is enzymes that sit in the synaptic cleft that are just chewing up neurotransmitters. [GIF]
🔸 The molecule that the neurotransmitter where degradation is really important is #acetylcholine.
So, in case of acetylcholine, there is an enzyme that sits between the pre-synaptic and the post-synaptic cells, eating up acetylcholine, called acetylcholinesterase (AChE).
🔸 Acetylcholine is the neurotransmitter that is used by motor neurons. And so, in fact, blocking #acetylcholinesterase can be used for therapeutics — in the case of people that are not releasing enough acetylcholine, or don't have enough receptors for the acetylcholine.
🔸 We can boost the amount of acetylcholine in the cleft by inhibiting the acetylcholinesterase. And that's useful for people with diseases such as myasthenia gravis.
Clostridial Toxins: #Botox
🔸 Botox is one of several clostridial toxins made by clostridial bacteria. And the full name of Botox is actually botulinum toxin.
🔸 The vesicles are held very close to the cell membrane. What holds them? A group of three proteins, two of them anchored in the cell membrane, one of them anchored in the vesicle membrane. This complex is called the snare complex.
🔸 And what happens when calcium comes in is that it changes snare complex's shape. Ca²⁺ changes snare's configuration to being in a straight line. [see GIF]
🔸 So that pushes the vesicle into the plasma membrane and fusion Is inevitable. It takes a lot of energy for them not to fuse, and when they're that close, it's inevitable.
🔸 It's the snare pin's sensitivity to calcium that is the final event that allows the vesicle to fuse with the cell membrane.
🔸 Botox comes in and cuts a particular protein of these proteins of the snare pin. But the clostridial toxins cut a variety of places in these three proteins that make up the snare pin.
🔸 If the snare pin is broken for whatever reason, if that is cut, then release doesn't happen.
🔸 Nowadays, we use clostridial toxins all the time — and we use them for very serious problems, such as focal dystonia, where there is an inappropriate continual contraction of a muscle, and that is a basal ganglia disorder.
💉 So, the Botox is injected at a very low dose, very locally.
And Botox is used for a large variety of treatments of various disorders. It's also used cosmetically.
🔸 And the interesting thing about it's use in cosmetics is that, before the widespread use of Botox, we made our own wrinkles. And what Botox is doing is preventing the motor neuron from releasing the neurotransmitter on to the muscle, and thereby preventing us from actively making our own wrinkles.
Babies who persistently struggle with sleep in their first year are more likely to have childhood anxiety https://t.co/ViVdRLX0Fc
https://twitter.com/MailOnline/status/1237593795010543618?s=09
New Intelligence on How the Female Brain Works - WSJ
https://www.wsj.com/articles/what-makes-the-female-brain-different-11583528929
The brain regions affected by declines in #estrogen during #menopause include the hypothalamus, which regulates body temperature; the brain stem, which regulates sleep and stress; the hippocampus, or memory center; and the amygdala, which is the emotional center of the brain.
🔸 How do we get the neurotransmitter out of the vesicle and out of the cell and make it able to go and affect another cell?
🔸 There is a cell membrane, but the cell also has a lot of other membranes that are inside. Inside in these things called organelles.
🔸 The fusion between two different membranes happens constitutively. And the challenge for a neuron is to stop that.
We can't have these vesicles fusing with the plasma membrane, with the cell membrane all the time. That would not work.
🔸 What we want to do is we want to make the vesicle fuse to the membrane **only when the action potential arrives** .
🔸 So the key to neurotransmitter release is two things:
1. We're going to suppress constitutive or ongoing release.
2. We are going to link the release that we want in the synaptic terminal to the action potential.
🔸 There is a molecule that suppresses constitutive release within the synaptic terminal.
🔸 When the action potential comes in, the membrane potential increases and it opens a particular type of ion channel that lets in calcium ions.
🔸 These are positively charged ions with two positive charges. And, these calcium ions are going to flood in to the synaptic terminal, and that is going to trigger release.
🔸 The release that happens of vesicles that contain neurotransmitters is only when the calcium concentration increases.
🔸 All that happens when the calcium concentration increases is that the vesicular membrane and the the cell membrane fuse.
And the calcium concentration only increases when the action potential arrives.
🖼️ Image source: screen-grab from https://www.coursera.org/learn/neurobiology/lecture/o4ZMY/neurotransmitter-release
The WALKING WATER Mystery (in SPACE and SLOW MOTION!) - Smarter Every Day 160
https://www.youtube.com/watch?v=KJDEsAy9RyM
🌱 ECO HOME: No Power, Water & Sewer connection in this house.
https://www.youtube.com/watch?v=LB5gzj0bmq0
New model is very good at predicting the charging time of a supercapacitor while also incorporating physics on the micro and nano scales. https://t.co/N7xGGWI81a
https://twitter.com/PhysicsWorld/status/1237389694918250496?s=09
Joined Nov 2019
