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I'm in the process of reading https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1564381/ and I'm trying to understand how the predicting is done in the neuron.
What I distilled so far: A cell gets an input, it calculates a probability of reward(bliss potential i like to call it), if it could cause a reward it releases dopamine in a quantity of expected reward.
So right now I'm wondering, what is the process that goes on to make that calculation. Which input variables does the neuron use to calculate the probability of a reward and how much dopamined to release?
Does it take account which synapses provided the input signals? Or is it the type of input signals? Or a combination of both? Is it the frequency inputs occur?
II need an explaination how the neuron calculates its "bliss potential" as i like to call it, in normal peoples english instead of academia english.
P.s. I don't have an academic background. I'm just interested in science related things without having a formal education.
Brain Dopamine Transmission in Health and Parkinson's Disease: Modulation of Synaptic Transmission and Plasticity Through Volume Transmission and Dopamine Heteroreceptors
This perspective article provides observations supporting the view that nigro-striatal dopamine neurons and meso-limbic dopamine neurons mainly communicate through short distance volume transmission in the um range with dopamine diffusing into extrasynaptic and synaptic regions of glutamate and GABA synapses. Based on this communication it is discussed how volume transmission modulates synaptic glutamate transmission onto the D1R modulated direct and D2R modulated indirect GABA pathways of the dorsal striatum. Each nigro-striatal dopamine neuron was first calculated to form large numbers of neostriatal DA nerve terminals and then found to give rise to dense axonal arborizations spread over the neostriatum, from which dopamine is released. These neurons can through DA volume transmission directly influence not only the striatal GABA projection neurons but all the striatal cell types in parallel. It includes the GABA nerve cells forming the island-/striosome GABA pathway to the nigral dopamine cells, the striatal cholinergic interneurons and the striatal GABA interneurons. The dopamine modulation of the different striatal nerve cell types involves the five dopamine receptor subtypes, D1R to D5R receptors, and their formation of multiple extrasynaptic and synaptic dopamine homo and heteroreceptor complexes. These features of the nigro-striatal dopamine neuron to modulate in parallel the activity of practically all the striatal nerve cell types in the dorsal striatum, through the dopamine receptor complexes allows us to understand its unique and crucial fine-tuning of movements, which is lost in Parkinson's disease. Integration of striatal dopamine signals with other transmitter systems in the striatum mainly takes place via the receptor-receptor interactions in dopamine heteroreceptor complexes. Such molecular events also participate in the integration of volume transmission and synaptic transmission. Dopamine modulation of the glutamate synapses on the dorsal striato-pallidal GABA pathway involves D2R heteroreceptor complexes such as D2R-NMDAR, A2AR-D2R, and NTSR1-D2R heteroreceptor complexes. The dopamine modulation of glutamate synapses on the striato-entopeduncular/nigral pathway takes place mainly via D1R heteroreceptor complexes such as D1R-NMDAR, A2R-D1R, and D1R-D3R heteroreceptor complexes. Dopamine modulation of the island/striosome compartment of the dorsal striatum projecting to the nigral dopamine cells involve D4R-MOR heteroreceptor complexes. All these receptor-receptor interactions have relevance for Parkinson's disease and its treatment.
Keywords: G protein-coupled receptor Parkinson's diseases dopamine receptor heteroreceptor complexes neural plasticity oligomerization volume transmission.
Illustration of how extrasynaptic dopamine…
Illustration of how extrasynaptic dopamine (DA) volume transmission modulates transmission of the striato-pallidal…
Illustration of how dopamine (DA)…
Illustration of how dopamine (DA) released from one DA varicosity via extrasynaptic volume…
Illustration of how dopamine (DA)…
Illustration of how dopamine (DA) release from DA varicosities can activate via volume…
Size Matters When It Comes to Cells' Vulnerability to Parkinson's
Each year doctors diagnose approximately 60,000 Americans with Parkinson&rsquos disease, an incurable neurodegenerative condition for which the number-one risk factor is age. Worldwide an estimated seven to 10 million people currently live with the malady. As U.S. and global populations grow older, it is becoming increasingly urgent to understand its causes.
So far, researchers know that Parkinson&rsquos involves cell death in a few restricted areas of the brain including the substantia nigra (SNc), one of two big cell clusters in the midbrain that house a large population of dopamine neurons. These cells release dopamine and are involved in a variety of functions including reward processing and voluntary movement. Their death leads to the motor control and balance issues that are core symptoms of the disease.
New research shows that these brain cells, most at risk in Parkinson&rsquos disease, require unusually high amounts of energy to carry out their tasks because of their highly branched structures. Like a massive car with an overheating engine, these neurons are susceptible to burnout and early death. This discovery emerged from a comparison of energy use in nigral dopamine neurons and in similar neurons found in the nearby ventral tegmental area (VTA), also in the midbrain. &ldquoWe were trying to understand why dopamine neurons of the substantia nigra die in Parkinson&rsquos disease patients while there are so many other brain cells that have no problem at all,&rdquo says Louis-Eric Trudeau, a neuroscientist at the University of Montreal and senior author of the study published in the August 27 Current Biology.
Although located nearly side by side, neurons in the SNc expended much larger amounts of energy than those in the VTA, and their mitochondria, the structures that create energy in cells, continuously worked at maximum capacity. On further examination, the researchers found that the huge demand of these energy-guzzling cells stemmed from the fact that they are about twice the size of their neighbors in the VTA. SNc neurons also have many more axonal extensions. Like a tree with many branches, the larger neurons require more energy to survive and carry out their functions.
When the experimenters reduced this branching by adding semaphorin, an axonal guidance protein that inhibits neural growth, it reduced mitochondrial activity, energy expenditure and vulnerability in these neurons. Unfortunately, such an approach would compromise surviving neurons, which need to increase their branching, especially in aging brains, to take over and replenish dopamine stores.
The hypothesis that extensive axonal branching contributes to the vulnerability of dopamine neurons implicated in Parkinson&rsquos has been suggested in the past, but this is the first study that puts these claims to the test&mdashin the lab at least. It remains to be seen if the findings also can be obtained in living animals, says André Parent, a professor at Laval University who studies neurodegenerative diseases and was not involved in the study.
All of us lose dopamine neurons as we age. This is not a problem for most people because as neurons are lost, other surviving ones take over. In some individuals, however, a &ldquocritical threshold&rdquo of neural loss is reached and the remaining cells are no longer able to compensate. &ldquoParkinson&rsquos is a multiple-hit disease,&rdquo Trudeau says. &ldquoTo develop the disease, you need a few things: the aging process and a mutation or exposure to environmental toxins. Perhaps all of us have neurons that are at risk that will eventually die in older age. But we don&rsquot have that second &lsquohit&rsquo that will increase the stress on these cells, leading to the development of the disease.&rdquo The large dopamine cells in the substantia nigra need extra energy to run, and this chronically elevated stress makes them more vulnerable to gene mutations, environmental effects and aging, all of which might be why they are some of the first to die off.
Trudeau and his team are now looking to use the findings from this discovery to improve rodent models of Parkinson&rsquos disease so that they are better able to mimic what happens in the primate brain. Because such brains are bigger, dopamine neurons have more territory to cover, likely requiring them to make more connections and expend more energy. Currently, scientists are not even sure that rats or mice develop Parkinson&rsquos at all, and it might be because their cells are too small. Future studies will hopefully reveal exactly how much size matters in brain.
The Neurochemicals of Happiness
Life in the human body is designed to be a blissful experience. Our evolutionary biology ensures that everything necessary for our survival makes us feel good. All animals seek pleasure and avoid pain. Therefore, our brain has a wellspring of self-produced neurochemicals that turn the pursuits and struggles of life into pleasure and make us feel happy when we achieve them.
This biological design is generous, but lays dormant in many. In this entry, I will look at seven brain molecules linked to happiness and offer simple ways you can trigger their release in your daily life.
The premise of The Athlete’s Way: Sweat and the Biology of Bliss is that through daily physicality and other lifestyle choices, we have the power to make ourselves happier. One of the side effects of living in a digital age is that we are increasingly removed from our physicality and each other.
Our biology is short-circuiting. The balance of neurochemicals that evolved for millennia has been disrupted by our modern lives, making us more prone to depression, anxiety and malcontent. Pharmaceutical companies are eager to readjust this imbalance with a pill. My goal is to prescribe simple lifestyle choices and changes in behavior that can improve your brain chemistry, make you feel better, and motivate you to maximize your human potential.
Our body produces hundreds of neurochemicals. Only a small fraction of these have been identified by scientists. We will not know in our lifetime exactly how all of these molecules work.
Albert Einstein believed that, "Everything should be made as simple as possible, but not simpler." Based on this philosophy, I have applied simple tags to seven brain molecules and general descriptions of how each is linked with a feeling of well-being.
The Neurochemicals of Happiness
1. Endocannabinoids: “The Bliss Molecule”
Endocannabinoids are self-produced cannabis that work on the CB-1 and CB-2 receptors of the cannabinoid system. Anandamide (from the Sanskrit “Ananda” meaning Bliss) is the most well known endocannabinoid. Interestingly, at least 85 different cannabinoids have been isolated from the Cannabis plant. The assumption is that each of these acts like a key that slips into a different lock of the cannabinoid system and alters perceptions and states of consciousness in various ways. It is likely that we self-produce just as many variations of endocannabinoids, but it will take neuroscientists decades to isolate them.
A study at the University of Arizona, published in April 2012, argues that endocannabinoids are, most likely, the cause for runner's high. The study shows that both humans and dogs show significantly increased endocannabinoids following sustained running.
The study does not address the potential contribution of endorphins to runner's high. However, in other research that has focused on the blood–brain barrier (BBB), it has been shown that endorphin molecules are too large to pass freely across the BBB, and are probably not responsible for the blissful state associated with the runner’s high.
2. Dopamine: “The Reward Molecule”
Dopamine is responsible for reward-driven behavior and pleasure seeking. Every type of reward seeking behavior that has been studied increases the level of dopamine transmission in the brain. If you want to get a hit of dopamine, set a goal and achieve it.
Many addictive drugs, such as cocaine and methamphetamine, act directly on the dopamine system. Cocaine blocks the reuptake of dopamine, leaving these neurotransmitters in the synaptic gap longer.
There is evidence that people with extraverted, or uninhibited personality types tend to have higher levels of dopamine than people with introverted personalities. To feel more extroverted and uninhibited, try to increase your levels of dopamine naturally by being a go-getter in your daily life and flooding your brain with dopamine regularly by setting goals and achieving them.
3. Oxytocin: “The Bonding Molecule”
Oxytocin is a hormone directly linked to human bonding and increasing trust and loyalty. In some studies, high levels of oxytocin have been correlated with romantic attachment. Some studies show if a couple is separated for a long period of time, the lack of physical contact reduces oxytocin and drives the feeling of longing to bond with that person again. But there is some debate as to whether oxytocin has the same effect on men as it does on women. In men, vasopressin (a close cousin to oxytocin) may actually be the “bonding molecule.” But again, the bottom line is that skin-to-skin contact, affection, lovemaking, and intimacy are key to feeling happy.
In a cyber world, where we are often "alone together" on our digital devices, it is more important than ever to maintain face-to-face intimate human bonds and "tribal" connections within your community. Working out at a gym, in a group environment, or having a jogging buddy is a great way to sustain these human bonds and release oxytocin.
In a 2003 study, oxytocin levels rose in both the dog and the owner after time spent "cuddling." The strong emotional bonding between humans and dogs may have a biological basis in oxytocin. If you don’t have another human being to offer you affection and increase oxytocin your favorite pet can also do the trick.
4. Endorphin: “The Pain-Killing Molecule”
The name Endorphin translates into “self-produced morphine." Endorphins resemble opiates in their chemical structure and have analgesic properties. Endorphins are produced by the pituitary gland and the hypothalamus during strenuous physical exertion, sexual intercourse, and orgasm. Make these pursuits a part of your regular life to keep the endorphins pumping.
Endorphins are linked less to "runner's high" now than endocannabinoids, but are connected to the "feeling no pain" aspect of aerobic exercise and are produced in larger quantities during high intensity "anaerobic" cardio and strength training.
In 1999, clinical researchers reported that inserting acupuncture needles into specific body points triggers the production of endorphins. In another study, higher levels of endorphins were found in cerebrospinal fluid after patients underwent acupuncture. Acupuncture is a terrific way to stimulate the release of endorphins.
5. GABA: “The Anti-Anxiety Molecule”
GABA is an inhibitory molecule that slows down the firing of neurons and creates a sense of calmness. You can increase GABA naturally by practicing yoga, meditation or “The Relaxation Response.” Benzodiazepines (Such as Valium and Xanax) are sedatives that work as anti-anxiety medication by increasing GABA. These drugs have many side effects and risks of dependency but are still widely prescribed.
A study from the Journal of Alternative and Complementary Medicine found a 27 percent increase in GABA levels among yoga practitioners after a 60-minute yoga session when compared against participants who read a book for 60 minutes. The study suggests yoga might increase GABA levels naturally.
6. Serotonin: “The Confidence Molecule”
Serotonin plays so many different roles in our bodies that it is really tough to tag it. For the sake of practical application I call it “The Confidence Molecule.” Ultimately the link between higher serotonin and a lack of rejection sensitivity allows people to put themselves in situations that will bolster self-esteem, increase feelings of worthiness, and create a sense of belonging.
To increase serotonin, challenge yourself regularly and pursue things that reinforce a sense of purpose, meaning, and accomplishment. Being able to say "I did it!" will produce a feedback loop that will reinforce behaviors that build self-esteem, make you less insecure, and create an upward spiral of more and more serotonin.
A variety of popular anti-depressants are called Serotonin-Specific Reuptake Inhibitors (SSRIs) — these are well known drugs like Prozac, Celexa, Lexapro, Zoloft, etc. The main indication for SSRIs is clinical depression, but SSRIs are frequently prescribed for anxiety, panic disorders, obsessive compulsive disorder (OCD), eating disorders, chronic pain, and post-traumatic stress disorder (PTSD).
SSRIs got their name because it was once thought they worked by keeping serotonin in the synaptic gap for longer and that this would universally make people who took these pills happier. Theoretically, if serotonin were the only neurochemical responsible for depression, these medications would work for everyone. However, some people never respond to SSRIs, but they do respond to medications that act on GABA, dopamine or norepinephrine systems.
Scientists do not fully understand the role of serotonin in mood-disorders which is why it is important that you work closely with a trusted psycho-pharmacologist if you want to find a prescription medication that works best for you. Also, the fact SSRIs take a couple weeks to kick in suggests that their effect may also have to do with neurogenesis, which is the growth of new neurons. These findings illustrate that how anti-depressants work in each person’s brain varies greatly and is not fully understood by scientists or researchers.
7. Adrenaline: “The Energy Molecule”
Adrenaline, technically known as epinephrine, plays a large role in the fight-or-flight mechanism. The release of epinephrine is exhilarating and creates a surge in energy. Adrenaline causes an increase in heart rate, blood pressure, and works by causing less important blood vessels to constrict and increasing blood flow to larger muscles. An “Epi-Pen” is a shot of epinephrine used in the treatment of acute allergic reactions.
An "adrenaline rush" comes in times of distress or facing fearful situations. It can be triggered on demand by doing things that terrify you or being thrust into a situation that feels dangerous. You can also create an adrenaline rush by taking short rapid breathes and contracting muscles. This jolt can be healthy in small doses, especially when you need a pick me up.
A surge of adrenaline makes you feel very alive. It can be an antidote for boredom, malaise, and stagnation. Taking risks, and doing scary things that force you out of your comfort zone is key to maximizing your human potential. However, people often act recklessly to get an adrenaline rush. If you’re an "adrenaline junkie," try to balance potentially harmful novelty-seeking by focusing on behaviors that will make you feel good by releasing other neurochemicals on this list.
There is not a one-size-fits-all prescriptive when it comes to creating a neurochemical balance that correlates to a sense of happiness. Use this list of seven neurochemicals as a rudimentary checklist to take inventory of your daily habits and to keep your life balanced. By focusing on lifestyle choices that secrete each of these neurochemicals, you will increase your odds of happiness across the board.
Brain science is a triad of electrical (brain waves), architectural (brain structures) and chemical (neurochemicals) components working in concert to create a state of mind. This entry focuses only on the chemical elements. I will explore the electrical and architectural components in future blogs.
The Evolving Understanding of Dopamine Neurons in the Substantia Nigra and Ventral Tegmental Area
In recent years, the population of neurons in the ventral tegmental area (VTA) and substantia nigra (SN) has been examined at multiple levels. The results indicate that the projections, neurochemistry, and receptor and ion channel expression in this cell population vary widely. This review centers on the intrinsic properties and synaptic regulation that control the activity of dopamine neurons. Although all dopamine neurons fire action potentials in a pacemaker pattern in the absence of synaptic input, the intrinsic properties that underlie this activity differ considerably. Likewise, the transition into a burst/pause pattern results from combinations of intrinsic ion conductances, inhibitory and excitatory synaptic inputs that differ among this cell population. Finally, synaptic plasticity is a key regulator of the rate and pattern of activity in different groups of dopamine neurons. Through these fundamental properties, the activity of dopamine neurons is regulated and underlies the wide-ranging functions that have been attributed to dopamine.
The Neurons That Appeared from Nowhere
T he scientists crowded around Yuanchao Xue’s petri dish. They couldn’t identify the cells that they were seeing. “We saw a lot of cells with spikes growing out of the cell surface,” said Xiang-Dong Fu, the research team’s leader at the University of California, San Diego. “None of us really knew that much about neuroscience, and we asked around and someone said that these were neurons.” The team, who were made up of basic cellular and molecular scientists, were utterly puzzled. Where had these neurons come from? Xue had left a failed experiment, a dish full of human tumor cells, in the incubator, and when he looked two weeks later, he found a dish full of neurons.
It’s not often an unexpected cell type appears in a petri dish, as if from nowhere. Scientists all over the world have spent a lot of time and money actively trying to generate neurons in the lab—the implications for neurodegenerative disease would be massive. And yet this research team, who were actually studying the RNA-binding protein PTB, had unknowingly generated a whole dish of neurons.
“It puzzled me for quite a long time, and I didn’t know what was wrong with my cells,” said Xue, who is now a researcher at the Institute of Biophysics at the Chinese Academy of Sciences, in Beijing. Xue was attempting to deplete human tumor cells of PTB with small interference RNAs (siRNAs). He expected his cell lines, which are typically very proliferative, to keep growing, but they stopped, and so were cast aside for two weeks. Sure that the dish had become contaminated, Xue and colleagues tried the experiment again … and again … and again.
Not being fully aware of the field, and how they were going against the science, helped them. Their naivety allowed them to push forward.
“We tested every cell we could grab, and every single time we did the same thing—that is removing the protein PTB—and every single cell became a neuron,” said Fu. Fibroblasts, tumor cells, glial cells … The team realized every time they depleted the cell of PTB, the cell would convert into a neuron. The logical next step was to move onto mouse models of Parkinson’s disease—the progressive death of dopamine-producing neurons that causes, among other things, tremor and movement problems. As with other neurodegenerative conditions, treatment is inherently difficult and current options are not curative. 1 Neurogenesis, the generation of new neurons in the brain, typically stops during puberty. So when these cells become damaged or die, the body cannot replace them.
Xue and his colleagues decided to concentrate on the substantia nigra, a region in the midbrain where dopaminergic neurons predominate and typically die during the disease. The researchers decided to try the depleting-PTB technique on astrocytes, star-shaped non-neuronal cells that are abundant in the brain. Usually they produce the RNA-binding protein PTB1, which prevents them from becoming neurons. Banking on the idea that when neurons die, astrocytes typically proliferate and fill up this space in the brain, the team thought it might be useful to convert these excess astrocytes in Parkinson’s disease into neurons in vivo, in animal models.
However, their neuroscientist peers were doubtful. In theory, Fue was told, it is not possible to regenerate a functional neuron or rebuild a neuronal circuit. Experiments in a petri dish, in vitro, can often look very different in vivo, in living organisms. What’s more, from an experimental perspective, the chances of converting astrocytes into functional neurons in vivo were looking slim.
Fu explained that not being fully aware of the field, and how they were going against the science, helped them. Their naivety, he said, allowed them to push forward. So, the team designed an adeno-associated virus to carry an siRNA, to silence the target gene that encodes PTB, Ptbp1. They injected the virus directly into the midbrain of the Parkinson’s mouse model, where the team had depleted most dopaminergic neurons with the chemical, oxidopamine. They also injected a control model with the siRNA without the vector. Fu and colleagues were able to see that 12 weeks after injection, the number of converted neurons had reached 30 to 35 percent there were no neurons in the control model. With a series of experiments thereafter, the researchers were also able to show that not only had the astrocytes converted to functional dopaminergic neurons, these neurons progressively matured and reconstructed neural circuits in the region and restored motor deficits. Neuroscientific theory was wrong.
Noise Is a Drug and New York Is Full of Addicts
As soon as the door slams, I slide to the floor in a cross-legged position and hold my breath. The room in which I have just barricaded myself looks a bit like Matilda’s chokey a single light bulb casts a. READ MORE
The team realized this technique could convert cell types into neurons specific to that region by injecting their virus-plus-vector into the cortical region of the brain, the researchers saw cortical astrocytes convert into cortical neurons. The team showed in a recent Nature paper, published in June of this year, that they had successfully reversed symptoms of Parkinson’s disease in a mouse model. 2
“Yes, these results are very unexpected,” said Xinnan Wang (who was not involved in the study) by email. Wang is a researcher in the department of neurosurgery at Stanford University School of Medicine. “[This is] a true ‘out of box’ innovation. If this mechanism works similarly in humans, it will provide a new paradigm for how we treat neurodegenerative disease including Parkinson’s disease: by simply converting patients’ own astrocytes to neurons.”
Other scientists have tried to do this before. A team from Sweden, for example, reported in a 2017 paper that they were able to convert astrocytes from a mouse with Parkinson’s disease into induced dopamine-releasing (iDA) neurons. 3 The conversion rate was low, however, and the iDA neurons were not able to build a distant neuronal circuit or completely restore motor behavior.
It may be that astrocytes are constantly suppressing their development into a neuron with the expression of PTB1. That’s one explanation for why removing PTB in astrocytes converted them to fully functioning neurons specific to the region.
“My dream is, before my retirement, we can see a clinical trial and a patient benefit from this.”
Despite Xue and colleagues’ series of elegant experiments, the researchers came up against a few hurdles. They originally submitted their study to another publication, back in 2017, but were rejected. “The three peer reviewers who had looked over the paper called us themselves to congratulate us,” said Fu. According to Fu, the reviewers raved, “This is so exciting” and “this is a major breakthrough.” Fu and the team were happy the research was well received. However, the publication’s editor was very hesitant. A fourth reviewer wondered if the team had interpreted their experiments correctly. The paper wasn’t accepted.
So, the disappointed team submitted their paper to Nature, where it was eventually published. But only after a few years and a lot more work. Yet again another set of reviewers immediately called the team to congratulate them on their “revolutionary work.” And a fourth reviewer suggested a set of experiments the researchers could do to cast away any further doubt. “They suggested 28 more experiments,” Fu said. “We did every single one. That’s why the paper is so long!”
“This is very exciting and (to me) an unexpected result from a theoretical point of view,” John Hardy, a researcher in the department of neurodegenerative disease at University College London, told Science Media Center, in London. “As a piece of basic science, it is really exciting. Whether it will help in the development of therapies for Parkisnon’s disease is much less clear … but exciting work.”
What’s next? “Larger animals,” said Fu. “Monkeys and then eventually humans and then specifically the aging human brain.” Fu isn’t under any illusion as to how much work and how many potential problems lie ahead of them. “My dream is, before my retirement, we can see a clinical trial and a patient benefit from this,” he said. “That would be nice.”
How—after their initial discovery, doubtful peers, countless rejected funding applications, and publication rejections—did Fu and his team find the perseverance to continue this research for a decade? Fu is humble, pointing to their naivety. “As basic scientists, we never dreamed we would run into this path of discovery. This was purely accidental.”
Wang added, “There are a lot of ‘accidents’ behind every single scientific discovery, and most of the time our projects do not turn out as originally planned. Then it is really important how the researchers treat these ‘accidents.’ Are these true scientific discoveries or just noises? Being a neuroscientist or not may not matter too much when unexpected results show up. I think what matters most is that the authors were able to pick this ‘accident’ up and push it forward.”
Nayanah Siva is a science writer based in London. Follow her on Twitter @nayanah.
1. Durães, F., Pinto, M., & Sousa, E. Old drugs as new treatments for neurodegenerative diseases. Pharmaceuticals 11, 44 (2018).
2. Qian, H., et al. Reversing a model of Parkinson’s disease with in situ converted nigral neurons. Nature 582, 550-556 (2020).
3. Rivetti di Val Cervo, P. Induction of functional dopamine neurons from human astrocytes in vitro and mouse astrocytes in a Parkinson’s disease model. Nature 35, 444-452 (2017).
Dopamine controls formation of new brain cells, salamander study shows
A study of the salamander brain has led researchers at Karolinska Institutet to discover a hitherto unknown function of the neurotransmitter dopamine. In an article published in the scientific journal Cell Stem Cell they show how in acting as a kind of switch for stem cells, dopamine controls the formation of new neurons in the adult brain. Their findings may one day contribute to new treatments for neurodegenerative diseases, such as Parkinson's.
The study was conducted using salamanders which unlike mammals recover fully from a Parkinson's-like condition within a four-week period. Parkinson's disease is a neurodegenerative disease characterised by the death of dopamine-producing cells in the mid-brain. As the salamander re-builds all lost dopamine-producing neurons, the researchers examined how the salamander brain detects the absence of these cells. This question is a fundamental one since it has not been known what causes the new formation of nerve cells and why the process ceases when the correct number have been made.
What they found out was that the salamander's stem cells are automatically activated when the dopamine concentration drops as a result of the death of dopamine-producing neurons, meaning that the neurotransmitter acts as a constant handbrake on stem cell activity.
"The medicine often given to Parkinson's patients is L-dopa, which is converted into dopamine in the brain," says Dr Andras Simon, who led the study at the Department of Cell and Molecular Biology. "When the salamanders were treated with L-dopa, the production of new dopamine-producing neurons was almost completely inhibited and the animals were unable to recover. However, the converse also applies. If dopamine signalling is blocked, new neurons are born unnecessarily."
As in mammals, the formation of neurons in the salamander mid-brain is virtually non-existent under normal circumstances. Therefore by studying the salamander, scientists can understand how the production of new nerve cells can be resumed once it has stopped, and how it can be stopped when no more neurons are needed. It is precisely in this regulation that dopamine seems to play a vital part. Many observations also suggest that similar mechanisms are active in other animal species too. Further comparative studies can shed light on how neurotransmitters control stem cells in the brain, knowledge that is of potential use in the development of therapies for neurodegenerative diseases.
"One way of trying to repair the brain in the future is to stimulate the stem cells that exist there," says Dr Simon. "This is one of the perspectives from which our study is interesting and further work ought to be done on whether L-dopa, which is currently used in the treatment of Parkinson's, could prevent such a process in other species, including humans. Another perspective is how medicines that block dopamine signalling and that are used for other diseases, such as psychoses, affect stem cell dynamics in the brain."
The salamander is a tailed member of the frog family most known for its ability to regenerate lost body parts, such entire limbs.
Materials provided by Karolinska Institutet. Note: Content may be edited for style and length.
Dopamine neurons have a role in movement, new study finds (Nature Neuroscience)
By Catherine Zandonella, Office of the Dean for Research
Princeton University researchers have found that dopamine – a brain chemical involved in learning, motivation and many other functions – also has a direct role in representing or encoding movement. The finding could help researchers better understand dopamine’s role in movement-related disorders such as Parkinson’s disease.
The researchers used a new, more precise technique to record the activity of dopamine neurons at two regions within a part of the brain known as the striatum, which oversees action planning, motivation and reward perception. The researchers found that while all of the neurons carried signals needed to learn and plan movement, one of the nerve bundles, the one that went to the region called the dorsomedial striatum, also carried a signal that could be used to control movements.
The work was published online in the journal Nature Neuroscience this week.
“What we learned from this study is that dopamine neurons that go to one part of the brain act differently than dopamine neurons that go to another part of the brain,” said Ilana Witten, assistant professor of psychology and the Princeton Neuroscience Institute. “This is contrary to what has been the mainstream view of dopamine neurons.”
The research may shed light on how Parkinson’s disease, which involves the destruction of dopamine neurons in the dorsomedial striatum, deprives patients of the ability to move. Previous studies have failed to find a direct link between dopamine neuron activity and the control of movement or actions. Instead, the mainstream view suggested an indirect role for dopamine: the neurons make it possible for us to learn which actions are likely to lead to a rewarding experience, which in turn enables us to plan to take that action. When dopamine neurons are destroyed, the individual cannot learn to plan actions and thus cannot move.
The new study affirmed the role of dopamine in reward-based learning, but also found that in the dorsomedial striatum, dopamine neurons can play a direct role in movement. The researchers used a method for measuring neuron activity at very precise locations in the brain. They measured the activity at the ends of neurons – the terminals where dopamine is released into the junction, or synapse, between two cells – in two locations in the striatum: the nucleus accumbens, known to be involved in processing reward, and the dorsomedial striatum, known for evaluating and generating actions.
Until recently, it has been difficult to measure dopamine neuron activity in these regions due to the small size of the regions and the fact that there are many other neurons present that are delivering other brain chemicals, or neurotransmitters, to the same areas of the brain.
To restrict their measurements to only dopamine-carrying neurons, the researchers used mice whose brains carry genetically altered cells that glow green when active. The mice also contain a second gene that ensured that the glowing could only occur when dopamine was present.
The researchers then recorded neuron activity from either the nucleus accumbens or the dorsomedial striatum by inserting a very thin optical fiber into each region to record the fluorescing dopamine cells in only the desired regions.
Once the ability to measure neuron activity was in place, the researchers gave the mice a task that involved both reward-based learning as well as movement.
The task involved presenting the mice with two levers, one of which, when pressed, gave a drink of sweetened water. Through trial and error, the mice learned which lever would give the reward. During the task, the researchers recorded their brain activity.
The task is analogous to playing slot machines at a casino. Picture yourself at a casino with two slot machines in front of you. You pull the lever on the machine to your left and it spits out some coins. Your brain learns that the left lever leads to a reward, so you plan and execute an action: you pull the left lever again. After a few more pulls on the left lever without a reward, you switch to the machine on the right.
When an action is rewarding, you are likely to remember it, an important step in learning. The difference between how much reward you expect, and how much you get, is also important, because it tells you whether or not something is new and how much you should pay attention to it. Researchers call this gap between your predicted reward and the reward you actually get the “reward-prediction error” and consider it an important teaching signal.
By matching the mice’s actions to the dopamine activity in their brains during these tasks, the researchers could determine which parts of the brain were active during reward-based learning, and which parts were active when choosing to press a lever. Assistance with computational modeling of the mice’s behaviors was provided by Nathaniel Daw, a professor of the Princeton Neuroscience Institute and Psychology.
The researchers found that the dopamine neurons that innervate the nucleus accumbens and the dorsomedial striatum did indeed encode reward-prediction cues, which is consistent with previous findings. But they also found that in the dorsomedial striatum, the dopamine neurons carried information about what actions the animal is going to take.
“This idea was that dopamine neurons carry this reward-prediction error signal, and that could indirectly affect movement or actions, because if you don’t have this, you won’t correctly learn which actions to perform,” Witten said. “We show that while this is true, it is certainly not the whole story. There is also a layer where dopamine is directly coding movement or actions.”
Nathan Parker, a graduate student in the Witten lab who designed and conducted the experiments and is first author on the paper, added that new findings were made possible both by the improvements in recording of neurons and by the experimental design, which gave researchers a detailed evaluation of neuron activity during a relatively complex task.
Additional research assistance was provided by Princeton postdoctoral research associates Courtney Cameron and Junuk Lee, and graduate student Jung Yoon Choi. Research Specialist Joshua Taliaferro, Class of 2015, begin working on the project as part of his senior thesis. The study also involved contributions from Thomas Davidson, a postdoctoral researcher at Stanford University.
The study also addresses the general question of how dopamine can be involved in so many functions in the brain, Witten said. “We think that some of the way that dopaminergic neurons achieve such diverse functions in the brain is by having specific roles based on their anatomical target.”
Naoshige Uchida, a professor of molecular and cellular biology at Harvard University who was not involved in the study, said the results challenge long-held views and open up new directions of research. “This study by the Witten lab elegantly shows that the activity of some dopamine neurons is modulated by the direction of motion,” Uchida said. “More importantly, they found some of the clearest evidence indicating the heterogeneity of dopamine neurons: A specific population of dopamine neurons projecting to the dorsomedial striatum encodes movement direction more so compared to another population projecting to the ventral striatum.”
Uchida continued, “A similar phenomenon has also been reported in an independent study in non-human primates (Kim, et al., Cell, 2015), suggesting that the Witten lab finding is more universal and not specific to mice. This is particularly important because dopamine has been implicated in Parkinson’s disease but how dopamine regulates movement remains a large mystery.”
Funding for the study was provided by the Pew Charitable Trusts, the McKnight Foundation, the Brain & Behavior Research (NARSAD) Foundation, the Alfred P. Sloan Foundation, the National Institutes of Health, the National Science Foundation, and Princeton’s Stuart M. Essig and Erin S. Enright Fund for Innovation in Engineering and Neuroscience.
186 Nervous System Disorders
By the end of this section, you will be able to do the following:
- Describe the symptoms, potential causes, and treatment of several examples of nervous system disorders
A nervous system that functions correctly is a fantastically complex, well-oiled machine—synapses fire appropriately, muscles move when needed, memories are formed and stored, and emotions are well regulated. Unfortunately, each year millions of people in the United States deal with some sort of nervous system disorder. While scientists have discovered potential causes of many of these diseases, and viable treatments for some, ongoing research seeks to find ways to better prevent and treat all of these disorders.
Neurodegenerative disorders are illnesses characterized by a loss of nervous system functioning that are usually caused by neuronal death. These diseases generally worsen over time as more and more neurons die. The symptoms of a particular neurodegenerative disease are related to where in the nervous system the death of neurons occurs. Spinocerebellar ataxia, for example, leads to neuronal death in the cerebellum. The death of these neurons causes problems in balance and walking. Neurodegenerative disorders include Huntington’s disease, amyotrophic lateral sclerosis, Alzheimer’s disease and other types of dementia disorders, and Parkinson’s disease. Here, Alzheimer’s and Parkinson’s disease will be discussed in more depth.
Alzheimer’s disease is the most common cause of dementia in the elderly. In 2012, an estimated 5.4 million Americans suffered from Alzheimer’s disease, and payments for their care are estimated at $200 billion. Roughly one in every eight people age 65 or older has the disease. Due to the aging of the baby-boomer generation, there are projected to be as many as 13 million Alzheimer’s patients in the United States in the year 2050.
Symptoms of Alzheimer’s disease include disruptive memory loss, confusion about time or place, difficulty planning or executing tasks, poor judgment, and personality changes. Problems smelling certain scents can also be indicative of Alzheimer’s disease and may serve as an early warning sign. Many of these symptoms are also common in people who are aging normally, so it is the severity and longevity of the symptoms that determine whether a person is suffering from Alzheimer’s.
Alzheimer’s disease was named for Alois Alzheimer, a German psychiatrist who published a report in 1911 about a woman who showed severe dementia symptoms. Along with his colleagues, he examined the woman’s brain following her death and reported the presence of abnormal clumps, which are now called amyloid plaques, along with tangled brain fibers called neurofibrillary tangles. Amyloid plaques, neurofibrillary tangles, and an overall shrinking of brain volume are commonly seen in the brains of Alzheimer’s patients. Loss of neurons in the hippocampus is especially severe in advanced Alzheimer’s patients. (Figure) compares a normal brain to the brain of an Alzheimer’s patient. Many research groups are examining the causes of these hallmarks of the disease.
One form of the disease is usually caused by mutations in one of three known genes. This rare form of early onset Alzheimer’s disease affects fewer than five percent of patients with the disease and causes dementia beginning between the ages of 30 and 60. The more prevalent, late-onset form of the disease likely also has a genetic component. One particular gene, apolipoprotein E (APOE) has a variant (E4) that increases a carrier’s likelihood of getting the disease. Many other genes have been identified that might be involved in the pathology.
Visit this website for video links discussing genetics and Alzheimer’s disease.
Unfortunately, there is no cure for Alzheimer’s disease. Current treatments focus on managing the symptoms of the disease. Because decrease in the activity of cholinergic neurons (neurons that use the neurotransmitter acetylcholine) is common in Alzheimer’s disease, several drugs used to treat the disease work by increasing acetylcholine neurotransmission, often by inhibiting the enzyme that breaks down acetylcholine in the synaptic cleft. Other clinical interventions focus on behavioral therapies like psychotherapy, sensory therapy, and cognitive exercises. Since Alzheimer’s disease appears to hijack the normal aging process, research into prevention is prevalent. Smoking, obesity, and cardiovascular problems may be risk factors for the disease, so treatments for those may also help to prevent Alzheimer’s disease. Some studies have shown that people who remain intellectually active by playing games, reading, playing musical instruments, and being socially active in later life have a reduced risk of developing the disease.
Like Alzheimer’s disease, Parkinson’s disease is a neurodegenerative disease. It was first characterized by James Parkinson in 1817. Each year, 50,000-60,000 people in the United States are diagnosed with the disease. Parkinson’s disease causes the loss of dopamine neurons in the substantia nigra, a midbrain structure that regulates movement. Loss of these neurons causes many symptoms including tremor (shaking of fingers or a limb), slowed movement, speech changes, balance and posture problems, and rigid muscles. The combination of these symptoms often causes a characteristic slow hunched shuffling walk, illustrated in (Figure). Patients with Parkinson’s disease can also exhibit psychological symptoms, such as dementia or emotional problems.
Although some patients have a form of the disease known to be caused by a single mutation, for most patients the exact causes of Parkinson’s disease remain unknown: the disease likely results from a combination of genetic and environmental factors (similar to Alzheimer’s disease). Post-mortem analysis of brains from Parkinson’s patients shows the presence of Lewy bodies—abnormal protein clumps—in dopaminergic neurons. The prevalence of these Lewy bodies often correlates with the severity of the disease.
There is no cure for Parkinson’s disease, and treatment is focused on easing symptoms. One of the most commonly prescribed drugs for Parkinson’s is L-DOPA, which is a chemical that is converted into dopamine by neurons in the brain. This conversion increases the overall level of dopamine neurotransmission and can help compensate for the loss of dopaminergic neurons in the substantia nigra. Other drugs work by inhibiting the enzyme that breaks down dopamine.
Neurodevelopmental disorders occur when the development of the nervous system is disturbed. There are several different classes of neurodevelopmental disorders. Some, like Down Syndrome, cause intellectual deficits. Others specifically affect communication, learning, or the motor system. Some disorders like autism spectrum disorder and attention deficit/hyperactivity disorder have complex symptoms.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Its severity differs from person to person. Estimates for the prevalence of the disorder have changed rapidly in the past few decades. Current estimates suggest that one in 88 children will develop the disorder. ASD is four times more prevalent in males than females.
This video discusses possible reasons why there has been a recent increase in the number of people diagnosed with autism.
A characteristic symptom of ASD is impaired social skills. Children with autism may have difficulty making and maintaining eye contact and reading social cues. They also may have problems feeling empathy for others. Other symptoms of ASD include repetitive motor behaviors (such as rocking back and forth), preoccupation with specific subjects, strict adherence to certain rituals, and unusual language use. Up to 30 percent of patients with ASD develop epilepsy, and patients with some forms of the disorder (like Fragile X) also have intellectual disability. Because it is a spectrum disorder, other ASD patients are very functional and have good-to-excellent language skills. Many of these patients do not feel that they suffer from a disorder and instead think that their brains just process information differently.
Except for some well-characterized, clearly genetic forms of autism (like Fragile X and Rett’s Syndrome), the causes of ASD are largely unknown. Variants of several genes correlate with the presence of ASD, but for any given patient, many different mutations in different genes may be required for the disease to develop. At a general level, ASD is thought to be a disease of “incorrect” wiring. Accordingly, brains of some ASD patients lack the same level of synaptic pruning that occurs in non-affected people. In the 1990s, a research paper linked autism to a common vaccine given to children. This paper was retracted when it was discovered that the author falsified data, and follow-up studies showed no connection between vaccines and autism.
Treatment for autism usually combines behavioral therapies and interventions, along with medications to treat other disorders common to people with autism (depression, anxiety, obsessive compulsive disorder). Although early interventions can help mitigate the effects of the disease, there is currently no cure for ASD.
Attention Deficit Hyperactivity Disorder (ADHD)
Approximately three to five percent of children and adults are affected by attention deficit/hyperactivity disorder (ADHD) . Like ASD, ADHD is more prevalent in males than females. Symptoms of the disorder include inattention (lack of focus), executive functioning difficulties, impulsivity, and hyperactivity beyond what is characteristic of the normal developmental stage. Some patients do not have the hyperactive component of symptoms and are diagnosed with a subtype of ADHD: attention deficit disorder (ADD). Many people with ADHD also show comorbitity, in that they develop secondary disorders in addition to ADHD. Examples include depression or obsessive compulsive disorder (OCD). (Figure) provides some statistics concerning comorbidity with ADHD.
The cause of ADHD is unknown, although research points to a delay and dysfunction in the development of the prefrontal cortex and disturbances in neurotransmission. According to studies of twins, the disorder has a strong genetic component. There are several candidate genes that may contribute to the disorder, but no definitive links have been discovered. Environmental factors, including exposure to certain pesticides, may also contribute to the development of ADHD in some patients. Treatment for ADHD often involves behavioral therapies and the prescription of stimulant medications, which paradoxically cause a calming effect in these patients.
Neurologists are physicians who specialize in disorders of the nervous system. They diagnose and treat disorders such as epilepsy, stroke, dementia, nervous system injuries, Parkinson’s disease, sleep disorders, and multiple sclerosis. Neurologists are medical doctors who have attended college, medical school, and completed three to four years of neurology residency.
When examining a new patient, a neurologist takes a full medical history and performs a complete physical exam. The physical exam contains specific tasks that are used to determine what areas of the brain, spinal cord, or peripheral nervous system may be damaged. For example, to check whether the hypoglossal nerve is functioning correctly, the neurologist will ask the patient to move his or her tongue in different ways. If the patient does not have full control over tongue movements, then the hypoglossal nerve may be damaged or there may be a lesion in the brainstem where the cell bodies of these neurons reside (or there could be damage to the tongue muscle itself).
Neurologists have other tools besides a physical exam they can use to diagnose particular problems in the nervous system. If the patient has had a seizure, for example, the neurologist can use electroencephalography (EEG), which involves taping electrodes to the scalp to record brain activity, to try to determine which brain regions are involved in the seizure. In suspected stroke patients, a neurologist can use a computerized tomography (CT) scan, which is a type of X-ray, to look for bleeding in the brain or a possible brain tumor. To treat patients with neurological problems, neurologists can prescribe medications or refer the patient to a neurosurgeon for surgery.
This website allows you to see the different tests a neurologist might use to see what regions of the nervous system may be damaged in a patient.
Mental illnesses are nervous system disorders that result in problems with thinking, mood, or relating with other people. These disorders are severe enough to affect a person’s quality of life and often make it difficult for people to perform the routine tasks of daily living. Debilitating mental disorders plague approximately 12.5 million Americans (about 1 in 17 people) at an annual cost of more than $300 billion. There are several types of mental disorders including schizophrenia, major depression, bipolar disorder, anxiety disorders and phobias, post-traumatic stress disorders, and obsessive-compulsive disorder (OCD), among others. The American Psychiatric Association publishes the Diagnostic and Statistical Manual of Mental Disorders (or DSM), which describes the symptoms required for a patient to be diagnosed with a particular mental disorder. Each newly released version of the DSM contains different symptoms and classifications as scientists learn more about these disorders, their causes, and how they relate to each other. A more detailed discussion of two mental illnesses—schizophrenia and major depression—is given below.
Schizophrenia is a serious and often debilitating mental illness affecting one percent of people in the United States. Symptoms of the disease include the inability to differentiate between reality and imagination, inappropriate and unregulated emotional responses, difficulty thinking, and problems with social situations. People with schizophrenia can suffer from hallucinations and hear voices they may also suffer from delusions. Patients also have so-called “negative” symptoms like a flattened emotional state, loss of pleasure, and loss of basic drives. Many schizophrenic patients are diagnosed in their late adolescence or early 20s. The development of schizophrenia is thought to involve malfunctioning dopaminergic neurons and may also involve problems with glutamate signaling. Treatment for the disease usually requires antipsychotic medications that work by blocking dopamine receptors and decreasing dopamine neurotransmission in the brain. This decrease in dopamine can cause Parkinson’s disease-like symptoms in some patients. While some classes of antipsychotics can be quite effective at treating the disease, they are not a cure, and most patients must remain medicated for the rest of their lives.
Major depression affects approximately 6.7 percent of the adults in the United States each year and is one of the most common mental disorders. To be diagnosed with major depressive disorder, a person must have experienced a severely depressed mood lasting longer than two weeks along with other symptoms including a loss of enjoyment in activities that were previously enjoyed, changes in appetite and sleep schedules, difficulty concentrating, feelings of worthlessness, and suicidal thoughts. The exact causes of major depression are unknown and likely include both genetic and environmental risk factors. Some research supports the “classic monoamine hypothesis,” which suggests that depression is caused by a decrease in norepinephrine and serotonin neurotransmission. One argument against this hypothesis is the fact that some antidepressant medications cause an increase in norepinephrine and serotonin release within a few hours of beginning treatment—but clinical results of these medications are not seen until weeks later. This has led to alternative hypotheses: for example, dopamine may also be decreased in depressed patients, or it may actually be an increase in norepinephrine and serotonin that causes the disease, and antidepressants force a feedback loop that decreases this release. Treatments for depression include psychotherapy, electroconvulsive therapy, deep-brain stimulation, and prescription medications. There are several classes of antidepressant medications that work through different mechanisms. For example, monoamine oxidase inhibitors (MAO inhibitors) block the enzyme that degrades many neurotransmitters (including dopamine, serotonin, norepinephrine), resulting in increased neurotransmitter in the synaptic cleft. Selective serotonin reuptake inhibitors (SSRIs) block the reuptake of serotonin into the presynaptic neuron. This blockage results in an increase in serotonin in the synaptic cleft. Other types of drugs such as norepinephrine-dopamine reuptake inhibitors and norepinephrine-serotonin reuptake inhibitors are also used to treat depression.
Other Neurological Disorders
There are several other neurological disorders that cannot be easily placed in the above categories. These include chronic pain conditions, cancers of the nervous system, epilepsy disorders, and stroke. Epilepsy and stroke are discussed below.
Estimates suggest that up to three percent of people in the United States will be diagnosed with epilepsy in their lifetime. While there are several different types of epilepsy, all are characterized by recurrent seizures. Epilepsy itself can be a symptom of a brain injury, disease, or other illness. For example, people who have intellectual disability or ASD can experience seizures, presumably because the developmental wiring malfunctions that caused their disorders also put them at risk for epilepsy. For many patients, however, the cause of their epilepsy is never identified and is likely to be a combination of genetic and environmental factors. Often, seizures can be controlled with anticonvulsant medications. However, for very severe cases, patients may undergo brain surgery to remove the brain area where seizures originate.
A stroke results when blood fails to reach a portion of the brain for a long enough time to cause damage. Without the oxygen supplied by blood flow, neurons in this brain region die. This neuronal death can cause many different symptoms—depending on the brain area affected— including headache, muscle weakness or paralysis, speech disturbances, sensory problems, memory loss, and confusion. Stroke is often caused by blood clots and can also be caused by the bursting of a weak blood vessel. Strokes are extremely common and are the third most common cause of death in the United States. On average one person experiences a stroke every 40 seconds in the United States. Approximately 75 percent of strokes occur in people older than 65. Risk factors for stroke include high blood pressure, diabetes, high cholesterol, and a family history of stroke. Smoking doubles the risk of stroke. Because a stroke is a medical emergency, patients with symptoms of a stroke should immediately go to the emergency room, where they can receive drugs that will dissolve any clot that may have formed. These drugs will not work if the stroke was caused by a burst blood vessel or if the stroke occurred more than three hours before arriving at the hospital. Treatment following a stroke can include blood pressure medication (to prevent future strokes) and (sometimes intense) physical therapy.
Some general themes emerge from the sampling of nervous system disorders presented above. The causes for most disorders are not fully understood—at least not for all patients—and likely involve a combination of nature (genetic mutations that become risk factors) and nurture (emotional trauma, stress, hazardous chemical exposure). Because the causes have yet to be fully determined, treatment options are often lacking and only address symptoms.
Parkinson’s disease is a caused by the degeneration of neurons that release ________.
________ medications are often used to treat patients with ADHD.
Strokes are often caused by ________.
- blood clots or burst blood vessels
Why is it difficult to identify the cause of many nervous system disorders?
- The genes associated with the diseases are not known.
- There are no obvious defects in brain structure.
- The onset and display of symptoms varies between patients.
- all of the above
Why do many patients with neurodevelopmental disorders develop secondary disorders?
- Their genes predispose them to schizophrenia.
- Stimulant medications cause new behavioral disorders.
- Behavioral therapies only improve neurodevelopmental disorders.
- Dysfunction in the brain can affect many aspects of the body.
Critical Thinking Questions
What are the main symptoms of Alzheimer’s disease?
Symptoms of Alzheimer’s disease include disruptive memory loss, confusion about time or place, difficulties planning or executing tasks, poor judgment, and personality changes.
What are possible treatments for patients with major depression?
Possible treatments for patients with major depression include psychotherapy and prescription medications. MAO inhibitor drugs inhibit the breakdown of certain neurotransmitters (including dopamine, serotonin, norepinephrine) in the synaptic cleft. SSRI medications inhibit the reuptake of serotonin into the presynaptic neuron.