Sections include: the autonomic nervous system, the endocrine system, basic behaviors, neuroimmunology, disorders of bodily regulation
Virtually every function of the body must work in coordination with others. For example, during competition an athlete needs more than a strong musculoskeletal system and keen senses— his or her cardiovascular system must increase blood pressure and heart rate to keep up with the physical exertion, the lungs must increase gas exchange,and the gastrointestinal system must provide adequate nutrients. Coordinating all of these systems is a crucial role of the brain. In particular, the brain stem, like a kind of autopilot, is responsible for reflexes that integrate bodily functions moment by moment. And the hypothalamus, processing signals from within the body and from the world around it, coordinates all these body systems with the way a person needs to behave.
Our brains collect information about the external world through the five senses: smell, taste, vision, touch, and hearing. At the same time, our brains also need to monitor many things about our internal worlds. They do this in two basic ways. First, the brain collects information about the internal organs through what are called visceral sensory nerves. The most important of these is the vagus nerve. It tells the brain how full and acidic the stomach is, what the body’s blood pressure is and how fast the heart is pumping, and whether the body is under attack from microbial invaders.
The second main way in which the brain judges what is happening in a person’s body is by monitoring the bloodstream. The brain shares the same blood as the rest of the body, after all. Its sensors detect the amount of oxygen and carbon dioxide in the blood, blood temperature, the presence of sugar and a variety of nutrients and minerals such as sodium, and levels of various chemical hormones, including the hormones made by white blood cells that signal infection or other inflammatory illnesses.
All of this information is necessary for the brain to detect disturbances in a person’s internal bodily state, or to respond to such threats as infectious disease. At the same time, our brains must coordinate all of these functions with our daily sleep-wake cycles, as well as the seasons of the year. To do this, the brain uses an internal clock mechanism: this measures time and keeps track of cues, such as the length of the day, to synchronize its timekeeping with the outside world. The brain thus sets up circadian rhythms that affect periods of rest and activity throughout the body. The most important cue it uses is sunlight, which travels from the eye directly to the hypothalamus, which is sensitive to it. We have learned to use such bright light to resynchronize people’s internal clocks if necessary.
The hypothalamus is thus the master regulatory site in the brain. It is a tiny area: out of the brain’s total three pounds (1,400 grams), it weighs only a bit more than an eighth of an ounce (4 grams). Yet the hypothalamus is necessary for a person to coordinate bodily function with behavior and the external world. It is the most protected part of the brain. It receives blood from all of the major blood vessels that supply the organ, protecting it from damage if one of those vessels is blocked by an ischemic stroke. It is also located in the deepest part of the brain, just behind the eyes in the middle of the head, so it is rarely injured by trauma.
The hypothalamus regulates bodily functions by coordinating three main systems:
■ the autonomic system of nerves that control all of the internal organs
■ the endocrine system, which provides hormones that direct the body’s organs
■ basic behaviors, such as eating, drinking, sleeping, and reproductive behavior
In addition, the hypothalamus’s activity influences the immune system.
The Autonomic Nervous System
The autonomic nervous system consists of three parts. The first is the sympathetic nervous system, which arises from the sympathetic ganglia, small collections of nerve cells lying alongside and in front of the spinal column. These ganglia are controlled by nerve cells in the spinal cord where it passes through the chest. The sympathetic nerves use norepinephrine as a neurotransmitter to chemically activate other tissues. One important component of the sympathetic nervous system is the adrenal gland, which releases epinephrine (also known as adrenaline). Sympathetic nerves prepare the body for “fight or flight”: they increase a person’s heart rate and blood pressure, cause sweating, make hair stand on end, and dilate the pupils. At the same time, they turn off systems, such as digestion, that are not immediately necessary in that situation.
The second component of the autonomic nervous system is the parasympathetic system. The parasympathetic nerves for most parts of the body, such as the vagus nerve, originate in the brain. Those that control the bowel and bladder originate in the lowest part of the spinal cord. These nerves use acetylcholine as a neurotransmitter, and their primary purpose is to help us rest and digest. They cue the secretion of saliva, tears, and mucus (in the respiratory tract) and of acid and enzymes in the stomach and intestines. They slow the heart and increase the rate of digestion in the gut, thus reversing the actions of the sympathetic nervous system.
The third component of the autonomic nervous system, the enteric nervous system, is often underrated. This system consists of the nerve cells embedded in the walls of the intestines. That may seem limited, but the enteric nervous system actually includes more cells than the other two branches of the autonomic nervous system combined. It controls the rate of peristalsis, or movement of food through the gut. This process is always going on, but it can be sped up or slowed down by the messages the enteric nerve cells receive through the parasympathetic or sympathetic channels.
All these autonomic reflexes are controlled by a person’s brain stem. Nerve cells in the medulla, the lowest part of the brain stem, manage blood pressure and heart rate. They increase respiration when the blood needs more oxygen, and increase blood flow to meet tissue demands. Other nerve cells in the medulla monitor how full the gastrointestinal tract is, regulate digestion, and even cause vomiting when things go wrong.
At a slightly higher level of the brain stem are nerve cells that coordinate these autonomic reflexes with behavior. These cells are in an area called the pons, and they contain two significant structures: the parabrachial nucleus coordinates how we hold our breath, chew, and swallow and integrates control of blood pressure with pain and emotion; Barrington’s nucleus controls bladder and bowel function, allowing us to rid our bodies of waste under socially acceptable conditions. However, the hypothalamus is necessary to tie all of these brain-stem reflexes together with ongoing behavior and emotion. For example, the hypothalamus increases blood pressure during an emotional experience.
The Endocrine System
The endocrine system controls how the brain and other tissues throughout the body produce and release hormones. The hypothalamus is the system’s key site in the brain. It manages the pituitary gland just below it, and it regulates the glands elsewhere in the body through the autonomic nervous system.
The pituitary gland is made up of two lobes, anterior and posterior, with separate functions. The posterior pituitary lobe is really a part of the brain and contains the axons of special neurons of the hypothalamus. It secretes two main hormones: oxytocin, involved in controlling birth and milk production, and vasopressin, which controls blood pressure and the release of excess water through the kidneys. The oxytocin and vasopressin are made by nerve cells in the hypothalamus, in the supraoptic and paraventricular nuclei. These neurons send their axons down the pituitary stalk, allowing them to release their hormones in the posterior pituitary lobe.
The anterior pituitary lobe is a gland located just in front of the posterior pituitary and is connected to the brain only by a special set of capillaries from the hypothalamus. It produces five hormones:
■ growth hormone, which stimulates growth and development throughout the body
■ thyroid-stimulating hormone, which activates the thyroid gland in the throat
■ adrenocorticotrophic hormone (ACTH), which signals the adrenal cortex to produce adrenal corticosteroids
■ luteinizing hormone and follicle-stimulating hormone, which stimulate the production of reproductive steroid hormones
■ prolactin, which prompts milk production
Neurons in the hypothalamus control the anterior pituitary lobe by secreting what are called releasing hormones. A portal vein carries these chemicals to the anterior pituitary lobe, which interprets them as signaling which hormones to release elsewhere in the body.
The rest of the endocrine system is made up of the gonads (ovaries and testes), the thyroid and parathyriod in the throat, the adrenal glands atop the kidneys, the islet cells in the pancreas, and the secretory cells lining the intestines (although there are many other organs that produce hormones, including the heart, which makes atrial natriuretic peptide, for example). These release a range of hormones, including estrogen, testosterone, and insulin. They direct everything from the body’s metabolism rate to how much calcium it retains to whether breasts develop. The secretion of their many hormones is controlled, at least in part, by autonomic nerves. For example, the secretion of insulin is controlled by both sympathetic and parasympathetic nerves that extend into the tissue of the pancreas. (This extension of nerves into other tissues is what brain scientists mean by the word innervation.) The whole system thus connects back to the hypothalamus.
The hypothalamus also plays a critical role in organizing basic behaviors necessary for us, or any large animals, to stay alive. It promotes specific behaviors that augment or, in some cases, go beyond what the hypothalamus can do through the other systems it directs. For example, virtually every animal needs to keep its temperature within a limited range around a setpoint. For humans, that setpoint is about 37°C (98.6°F). The hypothalamus regulates body temperature through the autonomic nervous system, which cues sweating, shivering, goose bumps, and the movement of blood to or from the skin. But another way not to get too hot or too cold is to seek an environment that is the right temperature. Even primitive animals like reptiles, whose autonomic nervous systems cannot regulate their temperature as ours
does, naturally seek an environment that produces an optimal body temperature. That behavior is driven by the hypothalamus.
Other fundamental aspects of behavior controlled by the hypothalamus include basic postures for feeding, sleeping, mating, or aggressive defense. The hypothalamus can also promote routine and repetitive behaviors, such as chewing, swallowing, shivering, or panting. These behaviors seem to be due to the hypothalamus’s stimulation of neural networks in the brain stem, not in the higher brain; animals will perform them under the right conditions even if the rest of their forebrain has been removed. On the other hand, a person needs an intact forebrain to effectively coordinate these behaviors into long-term survival strategies. The hypothalamic neurons involved in producing these behaviors also have outputs to the cerebral cortex, which may promote the initiation of specific behaviors. For example, neurons in the lateral hypothalamus that contain melanin-concentrating hormone are activated during starvation. They send signals directly to the cerebral cortex, where they may be involved in activating behaviors that contribute to feeding.
The hypothalamus coordinates autonomic, endocrine, and behavioral responses to satisfy a person’s basic life needs. Experiments by Walter Cannon and his colleagues at Harvard Medical School in the 1920s and 1930s showed that we need the hypothalamus to organize our patterns of behavior with coordinated autonomic and endocrine responses. Subsequent work has demonstrated that the hypothalamus operates the setpoints for a wide range of basic bodily functions: blood pressure, appetite, concentrations of glucose and salt in the blood, and others. It allows these functions to go only so far above or below the setpoint before it issues signals to restore the internal environment of the body to the healthful range. The hypothalamus is also critical for coordinating those functions with the external daynight and seasonal cycles. Furthermore, we rely on this part of the brain to provide effective responses to environmental challenges: an attack by a predator, invasion by a microorganism, hunger and thirst, and the presence of an appropriate mate. (For more, see our section about how the brain works these basic drives.)
A new perspective on the hypothalamus is taking shape from evidence suggesting that its activities also affect the immune system, and researchers have begun carefully studying how this may influence a person’s recovery from infections or some injuries. You might prefer to think of your immune system as a fully automatic response to viruses, bacteria, and other invaders, but the nervous system and immune system interact closely. Each constantly processes environmental cues and relays information to the other, using hormonal and other chemical messengers and the neuronal pathways.
These chemical messengers include interleukins— small proteins secreted by immune cells and other tissues. Interleukins in general act on the brain by causing cells along the blood vessels lining the brain to secrete prostaglandins. Prostaglandins cross the blood-brain barrier and cause manifestations of a systemic infection. You can block these with inhibitors of prostaglandin synthesis, such as aspirin. These proteins thus inform your brain when you are being affected by infection, inflammation, or any foreign substance.
A portion of the hypothalamus, the paraventricular nucleus, secretes a hormone called corticotrophin-releasing hormone. This hormone stimulates the pituitary gland, at the base of the brain, to secrete ACTH, which in turn stimulates the secretion of adrenal cortisol (a glucocorticoid). The pathway of this interaction is called the hypothalamic-pituitary-adrenal (HPA) axis. Cortisol at different concentrations has different effects. At natural concentrations—that is, concentrations not influenced by a drug treatment of some kind—cortisol suppresses immune responses. The HPA axis thus maintains a delicate balance and governs appropriate adjustments of the immune system during health.
When a person is exposed to stress, however, this balance breaks down, leading to increased susceptibility to infection or inflammation. During stress the brain releases large amounts of its stress hormones and induces the adrenal glands to produce more cortisol. High concentrations of cortisol suppress our immune responses and predispose the body to infection. Studies have shown that chronic psychological stress is associated with decreased immune responses, meaning more frequent and more severe infections. The following are some examples of these findings:
■ People exposed to greater perceived stress have an increased susceptibility to the viral-induced common cold.
■ Caregivers of people with Alzheimer’s disease have a decreased immune response to influenza vaccination.
■ Medical students produce fewer antibodies after hepatitis B vaccinations during examination periods.
There are also nerves running to such immune system organs as the spleen, thymus, and lymph nodes as part of the sympathetic and peripheral nervous systems (that is, outside the central nervous system). Together these systems regulate local inflammatory responses. At the sites of inflammation, the peripheral nerves release neuropeptides. Immune cells express receptors for these neuropeptides, allowing the cells to respond by causing inflammation, which is then involved in protection against bacteria and viruses.
In sum, the brain and immune system interact across a wide network. These two systems constantly communicate to maintain a healthy balance of immune responses. Disruptions of this regulated balance may lead to disease.
Disorders of Bodily Regulation
Awide range of diseases can affect the ability of an individual’s nervous system to govern his or her body’s systems. Because these systems are crucial to life, when they cannot perform consistently a person can suffer a great deal of damage. A person’s autonomic nerves may degenerate in Parkinson’s disease or in other disorders in which antibodies attack nerves, as in Guillain- Barré syndrome and other immune system diseases. The pathways in the brain that control the autonomic nerves may degenerate in certain neurological diseases, such as multiple-systems atrophy. Either problem may result in a person’s having difficulty maintaining blood pressure while standing, as well as a variety of digestive, bowel, and bladder problems.
Endocrine problems may result from a number of diseases that occur along the base of the brain, near where the pituitary stalk emerges from the hypothalamus. These include certain inflammatory diseases such as sarcoid, pituitary, and other rare tumors.
When the posterior pituitary lobe stops producing vasopressin, a person must urinate excessively and thus must drink a great deal as well; this condition is known as diabetes insipidus. On the other hand, when the lobe releases too much vasopressin, the body is unable to eliminate water;the resulting water intoxication may result in confusion or even seizures.
If the anterior pituitary lobe cannot secrete luteinizing or follicle-stimulating hormone, the result may be atrophy of the gonads. A person may not be able to tolerate cold without enough thyroid-stimulating hormone, will remain short if growth hormone is not secreted adequately before adolescence, and will be unable to resist stressful stimuli if ACTH is cut off. Interestingly, of all the anterior pituitary hormones, only prolactin is normally held back by the hypothalamus; if that control is impaired, the body’s levels of prolactin rise, which may result in unusual breast milk production and loss of menstrual cycles in women, or breast enlargement in men.
True hypothalamic injuries are very rare but very serious. Their effects depend on what part of the hypothalamus stops working correctly. If the medial hypothalamus is injured, a person may overeat badly and become obese. This problem can also cause atrophy of the gonads and loss of a woman’s menstrual cycle. Individuals with these injuries may become exceedingly aggressive as well. People with a developmental disorder known as Prader-Willi syndrome have similar symptoms, but the focus of the problem in these patients’ systems has not yet been identified.
Injuries to the lateral hypothalamus must occur on both sides of the brain to cause symptoms, and these are exceedingly rare. However, in rare cases such injuries may cause a person to stop eating and waste away. They may also impair the sleep-wake cycles, resulting initially in sleepiness but ultimately in narcolepsy, in which a person falls asleep suddenly or remains awake but loses the ability to move.
Occasionally, people with anterior hypothalamic injuries or developmental disorders have attacks in which their body temperature falls as low as 29°C (85°F), accompanied by coma. This rare regulatory disorder is called paroxysmal hypothermia, and its precise cause is not known.
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