2024-09-21

The Variabilities of Dopamine (₯) - PART III: CL:0000700 & SIO:000823

Fig 1: dopaminergic neurons (DAN) & curiosity
In the complex drama of the brain, there are many characters, but dopaminergic neurons (DAN) take the lead role. These neurons are always on the lookout for new things and solving puzzles, like a brainy Sherlock Holmes. Dopamine, the neurotransmitter, is their trusty sidekick, helping them stay curious and active.

But, like in any good story, there's a twist. Over time, these once-energetic neurons start to lose their zest for new experiences. This decline in curiosity mirrors our own aging. It raises an important question: what happens in the brain to cause this loss? What makes our inner Sherlock Holmes lose interest in the unknown?

Fig 2: underlying neural mechanisms of curiosity
Did you know? Inside your brain, there's a cell that looks like a thin ginseng root with branches that resemble ginseng whiskers. This fascinating cell is the dopaminergic neuron (DAN). When we see something new, it lights up the brain's circuits, making us want to explore, learn, and discover. DAN is like a detective in the brain, always drawn to new and unknown things, eager for excitement and new knowledge.

However, as we get older, this curiosity fades. Like a firework losing its spark, older people gradually lose interest in new things, both social and inanimate. Why is DAN so fascinated by new experiences? And as we age, what changes in DAN make it lose its curiosity?

It turns out that dopamine, a very versatile neurotransmitter, is not only linked to our happiness, desires, and goals but also closely connected to our "epistemic curiosity" and "empathic curiosity". As you read this, your brain is reacting, just like it would if you were really thirsty or hungry. The dopamine-sensitive areas in your midbrain light up—a phenomenon we call "epistemic curiosity." This curiosity drives us to explore and understand the world around us.

Fig 3: The knowledge tree of curiosity: SIO:000823

Another type of curiosity happens when we interact with other people. When we feel comfortable in social settings and try to understand what others are thinking and feeling, our brains release a lot of dopamine. This is called "empathic curiosity." Today, we are exploring how our curious detective, DAN, and dopamine play a role in triggering these two kinds of curiosity.

The Chinese version of Curiosity’s Knowledge Tree was added after the article was published on 2024/09/06. At the time of writing, popular science articles PART I and II based on the ontology hadn’t been published yet, so A.H. wasn’t sure if readers would like them. That’s why she wrote the articles on dopamine and curiosity using a traditional style. After Parts I and II were published, and readers loved them, she added information about curiosity by the Semanticscience Integrated Ontology (SIO) as shown in Figure 3. Curiosity is described as a positive emotion, related to desire.

To understand the connection, we need to look at dopamine, a chemical released by special neurons (called DAN) in the brain areas known as the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Studies using brain scans have shown that high levels of curiosity and new experiences increase activity in these areas. A 2023 study published in “Communications Biology” (a sub-journal of “Nature”) titled “Reduction in the activity of VTA/SNc dopaminergic neurons underlies aging-related decline in novelty seeking. ” looked at the brain mechanisms behind curiosity. It explained why our interest in new things decreases as we age. Through experiments with mice, the study showed that the reduction in activity of VTA and SNc neurons is a key factor in the decline of curiosity due to aging.

This
Fig 4: experiment on social and inanimate curiosity
study used mice to explore the relationship between brain neurons and curiosity, showing how these neurons affect curiosity. Figure 4 shows the results of testing curiosity about social interactions (making new mouse friends) and inanimate objects (like shiny toys) in young mice and older rats. Scientists observed that young mice are more curious and explore these new experiences more frequently than older rats. Over time, young mice's interest in new friends increases, while older rats show stable but lower curiosity levels.

In general, older rats are less curious compared to young mice. Researchers measured and analyzed the activity of dopamine neurons in the brain, finding that older rats have less spontaneous neuron activity.

They also used specific drugs to control dopamine release in the brain. When they reduced dopamine activity in older rats, the rats became less curious. When they increased dopamine activity in young mice, the mice became more curious. The study concluded that the number of dopamine neurons decreases with age, leading to less dopamine and lower curiosity in older individuals. In humans, we lose about 6% of certain neurons every decade, which reduces dopamine availability.


In simple terms, young and healthy dopaminergic neurons (DAN) can send signals on their own, without needing extra input. This means they can regularly fire up spontaneously. As we get older, these neurons become less active and send fewer signals, which is linked to a decrease in curiosity. It's like the aging brain dims the lights of curiosity. However, by boosting the activity of these neurons and increasing dopamine release, we might be able to prevent or improve the decline in curiosity and thinking skills caused by aging or Alzheimer's disease.

In the 1950s, when Einstein was 63, he wrote to a friend saying, “People like you and I, though mortal of course like everyone else, do not grow old no matter how long we live...[We] never cease to stand like curious children before the great mystery into which we were born.” While few can keep Einstein's level of curiosity, which drives exploration and learning, we now know that curiosity is closely linked to the chemical dopamine and the curious DAN neurons.

With this new knowledge, maybe the detective in our brains won't retire early. Instead, we might grow old gracefully, keeping our curiosity alive. This understanding gives us hope that our inner detective will keep looking for new and interesting things, allowing us to age with wisdom and wonder.

Fig 5: Different representative signals of dopamine, in addition to happiness, desire, motivational goals, etc., there is also curiosity

 

 

 

 

 

 

 

 

 




 

 

 

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2024-08-01

The Variabilities of Dopamine (₯) - PART II: CL: 0000700

CellsAtWork:dopaminergic neuron (DAN, CL: 0000700)
 
Hi everyone, I’m Dopamine Girl. As an organic compound, I am what chemist ChEBI calls 18243. My relationship with you humans can start from the Cell Ontology ID number 0000700 defined by biologists. The working cell is a dopaminergic neuron (DAN, CL: 0000700), a neuron (cell) that uses dopamine as the neurotransmitter. Without further ado, let’s look at Figure 1 to understand DAN’s work characteristics and knowledge genealogy.

Learn about cells and dopamine from the Cell Ontology (CL), mainly because the cell knowledge described by CL is pretty mature and complete (20 years ago from 2004), covering cell types from prokaryotes to mammals, though not including plants cell. The rich diversity of CL can be seen from that it has imported 17 external ontologies and been reused by 86 external ontologies. CL is also widely used, such as the Human Cell Atlas (the Human Cell Atlas) established in 2016 by an international research alliance composed of more than 3,000 biologists, informatics scientists, and clinicians from 99 countries, and the Human Cell Atlas of the National Institutes of Health in the United States. The HuBMAP project uses CL as its core resource as well.

Fig 1: DAN in the Cell Ontology.

In the Variabilities of Dopamine (₯) - PART I:ChEBI:18243, we introduced the father-child relationship in ontology, which is the up-and-down relationship of the knowledge structure or the "depth" of the ontology. In fact, the expression of depth in CL can be as deep as 31 levels, which is the 31 generations of the family tree in vernacular. Figure 1 shows the direct upper layer of DAN is the neuron that releases catecholamines as neurotransmitters - catecholaminergic neurons, namely the father of DAN. They inherit some characteristics of the three major cell families of neural, secretory and electrically activities, and therefore help us to easily grasp the characteristics of DAN as a working cell that releases and secretes dopamine.

Second, we are generally familiar with DAN, which resides in the midbrain, so DAN here is the target tissue for the major neurodegenerative pathologies when it comes to Parkinson's disease. DAN has two lower subcategories in the CL description, among which the midbrain dopaminergic neurons are the children of DAN. Since DAN will degenerate or decrease with age or disease, etc., if the brain cannot produce enough dopamine, the work responsible for transmitting messages cannot be performed normally, which may easily lead to the deterioration of body movements, cognitive sensory emotions, or hormones, as well as mediation and other related diseases.

Another neuron that lives in the inner nuclear layer of the retina, the so-called dopamanergic interplexiform cell, is also a child of DAN. It is not common in the general introduction of dopamine, and related research is relatively little. His specialty is the use of dopamine to regulate nerves in the retina to adapt to light. If he cannot use enough dopamine, it may also cause visual impairment in Parkinson's patients.

Nevertheless, compared to DAN's father-son relationship, siblings of DAN (left-right relationship) are more complicated. The CL ontology describes more than 2,700 cell types, including 660 types of nerve cells and more than 540 types of neurons. Fortunately, we have another body gang to rescue. The U.S. National Library of Medicine's Medical Subject Headings (MeSH) is 70 years old (published since 1954). From the Figure 2, you can learn about the working cell DAN in the nervous and cellular system from the MeSH knowledge tree, and the overview of its neuron cell siblings.

Fig 2: DAN in the MeSH tree

In the ontology, the relationship between father, son, brother and sister is the basic "blood relationship", and another relationship including the description of external knowledge is also the solid power of the ontology. Just like writing a biography, after the three generations of ancestors and grandchildren have been explained, the highlight is to narrate the protagonist's experience and meaningful events. For example, the chemical entity ChEBI:18243 introduced before has simple inclusion, similarity and application relationships. In the second part, our protagonist is a living cellular entity - dopaminergic neuron (DAN), so "biological process" becomes an indispensable element for interpreting knowledge. Through the external gene knowledge ontology (GO) imported into CL ontology, we can further understand the daily working status of biological processes of cellular DAN (Figure 3)

Working cells DAN are neurons that release dopamine through synapses. According to the definition of synapse by the GO ontology: the connection between the axon of one neuron and the dendrite, muscle fiber or glial cell of another neuron.

    Fig 3: DAN, dopamine & synapse base on GO ontology
  • The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell.
  •  As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane.
  • In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane.

The biological process of DAN (CL: 0000700) described by the cooperation of CL and GO ontology is shown in Figure 4. Its "relationship" or a grammatical metaphor for the relationship in the knowledge ontology is a verb:

  • has participant
  • has end location
  • results in acquisition of features of

The entities (metaphorically represented as nouns) involved in biological processes are:

  • Fig 4: DAN involved in biological processes, based on CL& GO ontologies　
    synaptic transmission, dopaminergic: The vesicular release of dopamine. from a presynapse, across a chemical synapse, the subsequent activation of dopamine receptors at the postsynapse of a target cell (neuron, muscle, or secretory cell) and the effects of this activation on the postsynaptic membrane potential and ionic composition of the postsynaptic cytosol. This process encompasses both spontaneous and evoked release of neurotransmitter and all parts of synaptic vesicle exocytosis. Evoked transmission starts with the arrival of an action potential at the presynapse.
  • dopaminergic neuron differentiation: The process in which a neuroblast acquires the specialized structural and functional features of a dopaminergic neuron, a neuron that secretes dopamine.
  • astrocyte-dopaminergic neuron signaling: Cell-cell signaling that mediates the transfer of information from an astrocyte to a dopaminergic neuron.

After learning some basic knowledge structure of dopamine as a chemical and working cells DAN, think about it again. If dopamine is multi-variable, then when DAN living in the midbrain releases dopamine, its impact on biology should undoubtedly be the same. Variable, and so on, what unexpected scientific commotion will dopaminergic neurons bring us then? (to be continued)

 

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2024-07-31

The must-reads of Psalms 1~23

 

Psalm 23: LORD is my shepherd: The Lord takes care of me as his sheep; I will not be without any good thing. He makes a resting-place for me in the green fields: he is my guide by the quiet waters. He gives new life to my soul: he is my guide in the ways of righteousness because of his name... https://vocus.cc/article/66a59f62fd89780001e8fa6e

Psalm 22: Lord, you give me faith: My God, my God, why are you turned away from me? why are you so far from helping me, and from the words of my crying? O my God, I make my cry in the day, and you give no answer; and in the night, and have no rest. But you are holy, O you who are seated among the praises of Israel... https://vocus.cc/article/667fbc98fd8978000177f707
 
Psalm21: Our delight in Your salvation!: The king will be glad in your strength, O Lord; how great will be his delight in your salvation! You have given him his heart's desire, and have not kept back the request of his lips. (Selah.) For you go before him with the blessings of good things: you put a crown of fair gold on his head... https://vocus.cc/article/6677c2affd8978000165d59b
Psalm 20: Lord give you all your requests: May the Lord give ear to you in the day of trouble; may you be placed on high by the name of the God of Jacob; May he send you help from the holy place, and give you strength from Zion; May he keep all your offerings in mind, and be pleased with the fat of your burned offerings; (Selah.)
https://vocus.cc/article/666d5beafd89780001847ddd
Psalm 19: night after night Lord gives Knowledge: The heavens are sounding the glory of God; the arch of the sky makes clear the work of his hands. Day after day it sends out its word, and night after night it gives knowledge. There are no words or language; their voice makes no sound... https://vocus.cc/article/6664fc9efd8978000128c5f8
Psalm 18: I will give you my love: Of the servant of the Lord, of David, who said the words of this song to the Lord on the day when the Lord made him free from the hand of all his haters, and from the hand of Saul; and he said,> I will give you my love, O Lord, my strength.The Lord is my Rock, my walled town, and my saviour; my God, my Rock, in him will I put my faith; ...

Psalm 17:Keep me as the light of your eyes: Let my cause come to your ears, O Lord, give attention to my cry; give ear to my prayer which goes not out from false lips. Be my judge; for your eyes see what is right. You have put my heart to the test, searching me in the night; you have put me to the test and seen no evil purpose in me; I will keep my mouth from sin. https://vocus.cc/article/6652c93afd89780001655bb0
Psalm 16: You will make clear to me the way: Keep me safe, O God: for in you I have put my faith. O my soul, you have said to the Lord, You are my Lord: I have no good but you. As for the saints who are in the earth, they are the noble in whom is all my delight. Their sorrows will be increased who go after another god: I will not take drink offerings from their hands, ... 
https://vocus.cc/article/664945e3fd89780001068b49
Psalm 15: Who may have a resting-place?: Lord, who may have a resting-place in your tent, a living-place on your holy hill? He who goes on his way uprightly, doing righteousness, and saying what is true in his heart; Whose tongue is not false, who does no evil to his friend, and does not take away the good name of his neighbour;
https://vocus.cc/article/663ebb6bfd89780001e3396a
Psalm 14: Lord is our support: The foolish man has said in his heart, God will not do anything. They are unclean, they have done evil works; there is not one who does good. The Lord was looking down from heaven on the children of men, to see if there were any who had wisdom, searching after God... https://vocus.cc/article/6636f2a7fd897800013de8b6

Psalm 13: Glad in YOUR salvation: Will you for ever put me out of your memory, O Lord? will your face for ever be turned away from me? How long is my soul to be in doubt, with sorrow in my heart all the day? how long will he who is against me be given power over me? Let my voice come before you, and give me an answer, O Lord my God; let your light be shining on me, so that the sleep of death may not overtake me
https://vocus.cc/article/662cbdfffd8978000123d831

Psalm 12：YOUR words are true words: Send help, Lord, for mercy has come to an end; there is no more faith among the children of men. Everyone says false words to his neighbour: their tongues are smooth in their talk, and their hearts are full of deceit. The smooth lips and the tongue of pride will be cut off by the Lord... https://vocus.cc/article/66231ceafd8978000134d0f9






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