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Basic Limbic Functions:
HOME:
Homeostasis: hypothalamus
Olfaction: olfactory cortex
Memory: hippocampal formation
Emotions: amygdala
Survival:
• Keeps the organism “running”
• Detect the environment
• Remember what was detected
• React accordingly
So here you have a diagram, basic diagram, very basic diagram, of limbic functions. What I want you to notice is a humongous amount of back and forth arrows that you have. These systems are highly interconnected. They are important for homeostasis, the hypothalamus in particular; olfaction, olfactory cortex; for memory, the hippocampal formation; for emotions, amygdala; and they are in charge of survival. So they are kind of very important.
They keep the organism drawn in. They are able to detect the environment and react, make the organism react accordingly. So there are many small creatures at sea, for instance, that may not have vision or audition, but they all have a limbic system, something that allows them to collect basic information about the environment and react, even if the reaction is just to escape from the predator. |
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• Ancient in origin
• Essential for survival
• Medial and ventral regions of the cerebral hemispheres
• Constitute the major portion of the forebrain in many species
• Only in higher mammals has the cortical mantle surpassed the limbic systems in size
• Its components are highly interconnected among them and with other systems |
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This is a ventral view of a human brain. And what you have in here is all of these blue areas that you see towards the center of the brain. So there you have an area that has to do with olfaction. Remember, olfaction is the only sensory system that bypasses the thalamus. It's because it's very ancient in origin. And this is what I was thinking, also, when I said small creatures that might be blind and so on, they might still have some sort of chemical sense that allows them to react to the environment. And those chemicals senses are somewhat similar, analogous, to olfaction.
So you have all of these areas around in the base of the brain that are limbic. You have the parahippocampal gyrus and so on, rhinal sulcus, part of some of the landmarks to be able to recognize |
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(Deep within the uncus lies the amygdala.)
In the sagittal view, it's again towards the center of the brain, and so the cingulate gyrus, and then, again, some parts of the subcallosal gyrus, as well as parahippocampal gyrus, parts of the uncus and the temporal pole, and so on. All of these blue areas are considered part of the limbic system. |
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Papez Circuit
James Papez, 1937: one of the major pathways of the limbic system—cortical control of emotions
There is an important circuit that is interesting to at least be aware of and sort of remember some of the details of it for historical reasons. And although much more is known now about that circuit at least, it is correct and it was the first one that was described in terms of describing pathways for the limbic system. And it also has to do with emotions. And it's a Papez circuit that was described by James Papez, 1937.
What you have is outputs from the parahippocampal gyrus that are coming out of entorhinal cortex, of course-- and then via the subiculum are going to make the fornix. The fornix is the set of actions that are traveling from this area of the parahippocampal gyrus. They're going towards the mammillary bodies. The cells of the mammillary body then-- mammillary bodies because you have two, one on each hemisphere-- are then going to send their actions to the anterior nucleus of the thalamus via the mammillothalamic track. And then from there, they come out in the internal capsule and go to the cingulate gyrus. And then they form the cingulate bundle and the information goes back to the parahippocampal gyrus-- of course not the same information, because information is being transferred and is being changed along the circuit.
Now, this loop, of course, involves extremely important structures. If you do something to any part of the loop in here, you will affect things such as memory. Remember that memory-- if I say hippocampus, you think of memory. If I say amygdala, think of emotions and fear. If I say cerebral cortex, think of higher cognitive functions, primary, motor, and somatosensory areas and so on. If I say cerebellum, think of fine tuning of motor information.
So if I say limbic, think of survival, and think of this circuit. If I say hippocampus, think of memory. With this, I want to end this part of the limbic system. |
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Definition
let's look at this view, a side view, of the different nuclei inside of the hypothalamus. By the way, when we say nuclei, we really mean nuclear complexes. And depending again on how you look at it, we try to keep it very simple.
We call, for instance, this as if it's one single medial preoptic nucleus. People doing research in the medial preoptic nucleus might then subdivide it into different parts. And then what happens is that you end up with a ton of different nuclear complexes. So I use extensively just complex and nucleus as if it's just one simple one.
So here you have the different components, color coded again. You can look at them yourselves. But I want to point out, if you think that makes it easy to remember. So if you get familiar with the structures-- here you have the pituitary again. And so here you have the optic chiasma.
So if we say suprachiasmatic, it means it is on top of the chiasma. That makes it easy to find. If something is anterior, it's towards the front. And if something is posterior, it's towards the back. So get familiar with the naming of the structures because a lot of the information that you need in order to be able to find a structure is contained within the name of the structure.
There are about 12, 14 different nuclei in nuclear complexes, in the hypothalamus. |
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Now, if we do a coronal cut of those different-- through the hypothalamus. I want to call attention to this particular one, that was not able to be seen in the previous representation. This is the lateral hypothalamatic nucleus.
This is the medial forebrain bundle. The medial forebrain bundle are fibers that are traversing, traveling through the nucleus. And they are represented here by a whole bunch of little dots. That means that the axons were cut in a transverse section. Here, of course, you have the optic chiasma for orientation also. |
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Hypothalamic neurons regulate body functions by:
1. Affectingbehaviorvia projections to other parts of the brain (e.g., frontal cortex)
2. Commanding hormone release from the pituitary gland
3. Regulating autonomic output through descending neural projections (via the spinal cord)
If you were to forget a lot of the details that I am giving you about the anatomy of the hypothalamus, remember function. Hypothalamic neurons regulate body functions. That's the main point. That's extremely important. The hypothalamus is absolutely essential for the regulation of every single important function that we can think of. And we'll look at a table of them, and also some diagrams to illustrate that point.
They affect behavior. They are projections to other parts of the brain. This is hypothalamic neurons. They command hormone release from the pituitary gland. And they regulate autonomic output to descending neuron projections. So here you have behavior hormones and projections to the autonomic nervous system. |
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How important are these functions? What is it that the hypothalamus is involved in doing, via the pituitary, for instance? You name it. Take your pick. All of them are extremely important.
Growth hormone, without the hormone you just don't grow. So growth hormone is important for our development. Take your pick here for reproduction. Hormones that have to do with the ovaries and the testes.
Problems with the hormones will represent reproductive problems. Reproductive problems, the species will die. If you cannot reproduce, that's the end of the species. Oxytocin and ADH, which is also called vasopressin, extremely important again for survival, for the going on of the species, for everything that we have to do that has to do with keeping us alive and alive as a species and able to reproduce, able to function, able to develop, able to grow, and so on
Here you have prolactin for milk production. A mother doesn't produce milk or the baby is unable to deal with the milk, simply will not survive. |
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Now, I want you to also look quickly at the hypothalamic-hypophyseal portal system and note these important differences. And this is again something that we don't have time to go into a lot of details. But it's important for you to at least recognize some important differences.
Important differences are that things that are going-- hormones-- that are going here to the posterior pituitary, are directly released into the cells of posterior pituitary. On the other hand, to the anterior pituitary-- and I'm going to make a much bigger deal about the anterior pituitary-- get released into the blood, into the blood system. And it is then the blood that will bring these substances down to the anterior pituitary. That is what we call the hypophyseal system, portal system. |
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And this is what I tried to put here in the table because I thought it is much easier to follow. So the organization of the table, that will help you to understand the material and to remember some of it, goes as follows.
Here you have the hypothalamic-pituitary-adrenal axis or HPA axis. Then an HPT, the hypothalamic-pituitary-thyroid axis. And then hypothalamic-pituitary-liver access. So you follow the logic. I think that makes it easy.
Here, at the second level, at this level, I put some of the nuclei that might be particularly in both for those functions. So the PVN-- the PVN, the medial-dorsal, the preoptic, and some unknown nuclei. These are subjects of research.
Then what I have at this level here is the particular cells that are in this nucleus, that are releasing something into the cells of the anterior pituitary So here you have the anterior pituitary. Here you have the hypothalamus. So, again, this is just a way to make things a little bit easier to follow.
So in this case, you have corticotropin-releasing hormone, CRH. Keep in mind in some textbooks the authors might keep changing hormone and factor. So I tried my best to be consistent. But there are even debates as to when a hormone should be called a hormone and when it should be called a factor, and so on. But we are not going to get into those debates.
So I am calling CRH, corticotropin-releasing hormone. Where is it going to be released, in cells of the anterior pituitary? Which ones? In the ones that we call corticotropes, corticotropes.
And they will produce ACTH, adrenocorticotropic hormone. And this is what is going to be released on the adrenal gland. The adrenal gland will then release cortisol. And all of these systems, as far as we understand and as little as we know about them, all of them have feedback mechanisms. I avoided to put positive and negative signs in here. But I will show you at least a couple of examples.
The point that I want to make is all of them have feedback mechanisms because you need to be able to somehow usually shut off the system. You don't want to continue releasing cortisol. So the usual effect is going to be a feedback mechanism that is going to tell, at least at one or two levels, OK, enough, turn off the faucet because we don't want this to continue.
The same thing happens here with the thyroid-releasing hormone, and the growth hormone, and so on. Again, I put the information in this manner to make it a little bit easier to follow. |
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Now, I'm going to pick this particular one to give you an example that might be found in textbooks and so on. This is various synaptic inputs are coming into the hypothalamus. Then you have your corticotropin-releasing hormone. It's going to the anterior pituitary. This lobe here is anterior. This part is posterior.
So the anterior pituitary will have adrenocorticotropic hormone being released on the adrenal gland. And the adrenal gland will release cortisol. And that cortisol, as I said previously, now negative, have a negative effect in here.
So it's going to inhibit, if you would, the continuous release of more of these factors or hormones. That's a feedback mechanism to control itself. So this is just one example.
The other ones follow very similar pathways. For some of the cases, there is more that we do not know. There is missing information. It is difficult sometimes to study these systems, especially in human, because certain experiments cannot be done in human for obvious reasons.
So, of course, there is lack of information. But all of these are very hot topics of research. And all of them are extremely important, as I mentioned before, for survival and for the ongoing of the species as a species. With this, I want to conclude this part of our discussion. |
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Definition
(circa = around; diem = day)
• Present in animals,plants,bacteria,etc.
• In human: develops postnatally |
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| Circadian rhythmicity is present in: |
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Definition
• Sleeping
• Feeding
• Core body temperature
• Brain wave activity
• Hormone production, etc. |
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| Criteria to be a circadian rhythm: |
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Definition
1. Must repeat once a day (~every 24-hour cycle: biochemical, physiological, and behavioral)— daylight
2. Must persist in the absence of external cues (endogenously driven)
3. Must be entrainable (adjustable to local time)
4. Must maintain periodicity over a range of physiological temperatures (exhibit temperature compensation) (circadian clock must maintain ~24 hours period despite cellular changing kinetics, particularly of temperature) |
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Important phase markers for human (mammal’s) circadian rhythm: Melatonin secreted from the pineal gland
Core body temperature
Plasma level of cortisol
Sleep is a circadian rhythm that is time-locked to the day-night cycle.
A person’s activity while awake, following isolation from time cues, shows that there is an endogenous rhythm that is ~24 hours. This rhythm is set up by the suprachiasmatic nucleus of the hypothalamus (SCN).
. And what you have here is a diagram depicting results of experiments that have been already conducted, that we're able to determine this.
And what the idea is that you have people that were in isolation from time cues. In other words, they were unable to determine if it was daylight, or dark, or what time it was. And they were kept in a particular place. And then what was found is that circadian rhythmicity continues. It will continue to occur in the absence of cues. This is repeatable with animals, of course. And then, through several studies, it was determined that the SCN-- the suprachiasmatic nucleus-- is absolutely essential for circadian rhythmicity. So suprachiasmatic-- remember, on top of the chiasma. Now you know where it is as well. |
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Circadian nature of sleep: suprachiasmatic nucleus (SCN)
Two phases of sleep: REM and non-REM
Ascending activating systems and arousal
This is another result, which is shown in here, showing hours in culture versus vasopressin release in picograms per milliliter per hour-- and extremely important for sleep. There are two phases, obviously, again-- REM, which is rapid eye movement, and non-REM. And we have discussed some of this before and some of the characteristics. |
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And what you have here is a diagram depicting results of experiments that have been already conducted, that we're able to determine this.
And what the idea is that you have people that were in isolation from time cues. In other words, they were unable to determine if it was daylight, or dark, or what time it was. And they were kept in a particular place. And then what was found is that circadian rhythmicity continues. It will continue to occur in the absence of cues. This is repeatable with animals, of course. And then, through several studies, it was determined that the SCN-- the suprachiasmatic nucleus-- is absolutely essential for circadian rhythmicity. So suprachiasmatic-- remember, on top of the chiasma. Now you know where it is as well.
This is another result, which is shown in here, showing hours in culture versus vasopressin release in picograms per milliliter per hour-- and extremely important for sleep. There are two phases, obviously, again-- REM, which is rapid eye movement, and non-REM. And we have discussed some of this before and some of the characteristics. So here you have a couple of diagrams showing, on the one hand, different stages of sleep, and on the other, the characteristics of the EEG-- the electroencephalographic-- activity that could be detected.
Now, I mentioned this before, but I'm going to repeat it. It is very interesting that this low voltage fast activity that is typical of being awake, and being paying attention, and active, and so on, it slows going down into sleep-- the more drowsy you feel and the more you go deep into falling asleep-- it converts into slow-wave activity in the EEG. And then finally, when you are deeply asleep, it goes back to your activity, which is extremely similar to being awake. That's the rapid eye movement-- the REM-- sleep. And again, it's low voltage fast activity, as you can see here.
Now, interesting for many reasons-- both physiological reasons as well as well as being able to follow the anatomy of the structures that are involved, and so on. But I find-- at this point, I want to tell you something that is a personal opinion. I find it extremely interesting to think that we have evolved a lot of different mechanisms to be able to survive.
Pain is there for us to be able to survive. Fear is there for us to be able to survive. When you don't have fear, you usually end up dead very quickly. And then comes sleep. I mean, we fall asleep. We sleep about 1/3 of our lifetime if you sleep eight hours a day. And this seems to go completely backwards from evolution, which would have evolved to be awake all the time, if being alive is important.
When you fall asleep, you are easy prey. So there must be extremely important functions for sleep. They have to override the risks of many other important functions that have been put in place by evolution. So just keep that in mind when you think how important it is to fall asleep and to have good sleep. |
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Definition
| Here you have some of the rhythms of the cortex again, that this is a repetition from stuff that we have done before. And again, just to make the point that all of this activity, whether you are sleeping or not, we are able to detect via electroencephalograms. |
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| Characteristics of REM sleep: |
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Definition
• Rapid eye movements
• EEG activation (low voltage fast activity)
• Other muscles (than the ones moving the eyes) show low tone due to descending inhibition of motor neurons
• In humans, about two hours of REM sleep and dreams per night
• Typically not remembered unless awoken during or immediately after dream
• Dreams occur in real time
• Dreams: most often visual, then auditory, sometimes temperature, only rarely tactile, olfactory, or taste
• Dream-emotional content: typically anxiety, surprise, joy, sadness, shame |
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| noradrenergic, serotoninergic, histaminergic neurons |
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One system which is active is the cholinergic system. A lot of cholinergic cells in the base of our brain are active and they are keeping the rest of the cortex active. And that seems to be a main mechanism. Cholinergic input from the base of our brain in primates and humans-- the nuclear basalis of Meynert seems to be in both, and keeping-- it's an arousal system-- and is keeping the cortex awake. So all the mechanisms downstream from the base of our brain are responsible for making sure that the dreams are not being active and that the motor systems are completely depressed.
So you can look at these details in here. And pay attention to what is going on with the different neurotransmitter systems. And this is the one I'm just talking about a second ago-- inhibition tonic, inhibition of muscle activity. So that you don't really want to get up and start walking or anything like that. So there are systems which are active during REM sleep and differences with some of the systems which are active during non-REM sleep. And those differences are important, again, in terms of what is happening in terms of sleep. |
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Definition
• Process by which the body maintains blood osmolality at ~300
mOsmol/kg
• Osmolality (ratio of salt to water): increases in blood—when salt content increases (e.g., eat salty crackers), or water decreases (e.g., by sweating triggered for thermoregulation; diarrhea, etc.)
• Osmolality decreases in blood: when we ingest hypotonic fluids
• Extremes can kill you; why?
• Cells either shrink or swell
• The brain is particularly sensitive; changes of 10 mOsmol/kg in blood osmolality can cause headaches, >10 mOsmol/kg can cause mental confusion, seizures, coma—death.
• Thirst kills you and—yes, drinking a lot of water at once can kill you too. |
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| fever! Physiological range for proper function is rather narrow |
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Definition
• Sexualfunctions:(erectile)dysfunction • Reproduction: pregnancy
• Milk production: menopause
• Feeding: obesity
• Mood
• Premenstrual syndrome
• Depression
• Anxiety
• Fear |
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Definition
• Insomnia,sleepapnea
• Narcolepsy:excessivesleepiness,extreme fatigue—person falls asleep at wrong time
• Cataplexy:muscularweakness—maybecollapse— but hearing and awareness remain normal; may be triggered by strong emotional reactions—affects ~70% of people with narcolepsy; motor neurons that are normally inhibited during sleep are abnormally disinhibited— hypocretin (orexin) mediated
• Restlesslegsyndrome REM behavior disorder
Circadian rhythm disorders |
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Definition
• Mode of action: nonselective antagonist of adenosine receptors (binds to adenosine receptor, but does not activate them); side effects: competitive nonselective PDE inhibitor, increases intracellular cAMP, activates PKA, etc.—interferes with sleep
• Effects in organs other than brain: e.g., caffeine binds to beta- adrenergic receptors on the surface of heart muscle cells, causes increase in cAMP inside cells |
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Definition
• Mode of action: serotonin, norepinephrine, dopamine reuptake
inhibitor
• Addictive: possibly via the mesolimbic DA reward pathway; topical anesthetic
• Stimulant of CNS: increases alertness, well-being—euphoria, energy, motor activity, etc.; appetite suppressant |
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Definition
• Mode of action: mimics endorphins—rapid acting narcotic—acts on m-opioid receptors
• Potent opiate analgesic drug—constipation, addiction, overdose (~200 mg) causes asphyxia, etc |
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Definition
• Mode of action: multiple: hydroxy groups can affect biochemical
reactions—can form unwanted hydrogen bonds, etc.
• Causes drunkenness—hangover (intoxication)—dehydration, etc. |
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| Social Impact of lack of sleep |
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Definition
• Exxon Valdez: at Prince William Sound, Alaska; March 24, 1989
• Spilled: 260,000 barrels of crude oil
Numerous plane crashes: pilot vs. controller
Sleep-alcohol-drugs
Numerous car accidents
-coffee can help |
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