Neural top–down control of physiology concerns the direct regulation by the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

of physiological functions (in addition to

smooth muscle Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...

and

glandular In animals, a gland is a group of cells in an animal's body that synthesizes substances (such as hormones) for release into the bloodstream (endocrine gland) or into cavities inside the body or its outer surface (exocrine gland). Structure De ...

ones). Cellular functions include the immune system’s production of

T-lymphocytes A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell rec ...

and

antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

, and nonimmune related

homeostatic In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and i ...

functions such as

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

gluconeogenesis Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrat ...

, sodium reabsorption,

osmoregulation Osmoregulation is the active regulation of the osmotic pressure of an organism's body fluids, detected by osmoreceptors, to maintain the homeostasis of the organism's water content; that is, it maintains the fluid balance and the concentration o ...

, and

brown adipose tissue Brown adipose tissue (BAT) or brown fat makes up the adipose organ together with white adipose tissue (or white fat). Brown adipose tissue is found in almost all mammals. Classification of brown fat refers to two distinct cell populations with si ...

nonshivering thermogenesis. This regulation occurs through the sympathetic and

parasympathetic The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of t ...

system (the

autonomic nervous system The autonomic nervous system (ANS), formerly referred to as the vegetative nervous system, is a division of the peripheral nervous system that supplies viscera, internal organs, smooth muscle and glands. The autonomic nervous system is a control ...

), and their direct innervation of body organs and tissues that starts in the

brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is cont ...

. There is also a noninnervation

hormonal A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required fo ...

control through the

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...

and

pituitary In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The hypop ...

(

HPA HPA may refer to: Organizations * Harry Potter Alliance, a charity * Halifax Port Authority, Canada * Hamburg Port Authority, Germany * Hawaii Preparatory Academy, a school in Hawaii, US * Health Protection Agency, UK * Heerespersonalamt, the Ger ...

). These lower brain areas are under control of

cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of ...

ones. Such cortical regulation differs between its left and right sides.

Pavlovian conditioning Classical conditioning (also known as Pavlovian or respondent conditioning) is a behavioral procedure in which a biologically potent stimulus (e.g. food) is paired with a previously neutral stimulus (e.g. a triangle). It also refers to the learni ...

shows that brain control over basic cell level physiological function can be learned.

Higher brain

Cerebral cortex

Sympathetic and

nervous systems and the

are regulated by the higher brain. Through them, the higher cerebral cortex areas can control the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

, and the body’s

and

stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...

physiology. Areas doing this include the

insular cortex The insular cortex (also insula and insular lobe) is a portion of the cerebral cortex folded deep within the lateral sulcus (the fissure separating the temporal lobe from the parietal and frontal lobes) within each hemisphere of the mammalian bra ...

, the orbital, and the medial prefrontal cortices. These cerebral areas also control smooth muscle and glandular physiological processes through the sympathetic and parasympathetic nervous system including

blood circulation The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...

urogenital The genitourinary system, or urogenital system, are the organs of the reproductive system and the urinary system. These are grouped together because of their proximity to each other, their common embryological origin and the use of common pathwa ...

gastrointestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

functions, pancreatic gut secretions,

respiration Respiration may refer to: Biology * Cellular respiration, the process in which nutrients are converted into useful energy in a cell ** Anaerobic respiration, cellular respiration without oxygen ** Maintenance respiration, the amount of cellula ...

coughing A cough is a sudden expulsion of air through the large breathing passages that can help clear them of fluids, irritants, foreign particles and microbes. As a protective reflex, coughing can be repetitive with the cough reflex following three phas ...

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...

piloerection Goose bumps, goosebumps or goose-pimples are the bumps on a person's skin at the base of body hairs which may involuntarily develop when a person is tickled, cold or experiencing strong emotions such as fear, euphoria or sexual arousal. The f ...

pupil The pupil is a black hole located in the center of the iris of the eye that allows light to strike the retina.Cassin, B. and Solomon, S. (1990) ''Dictionary of Eye Terminology''. Gainesville, Florida: Triad Publishing Company. It appears black ...

dilation,

lacrimation Tears are a clear liquid secreted by the lacrimal glands (tear gland) found in the eyes of all land mammals. Tears are made up of water, electrolytes, proteins, lipids, and mucins that form layers on the surface of eyes. The different types of ...

and

salivation Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be e ...

Lateralization

The sympathetic nervous system is predominantly controlled by the right side of the brain (focused upon the insular cortex), while the left side predominantly controls the parasympathetic nervous system. The cerebral cortex in rodents shows lateral specialization in its regulation of immunity with immunosuppression being controlled by the right hemisphere, and immunopotention by the left one. Humans show similar lateral specialized control of the immune system from the evidence of

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

s, surgery to control

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...

, and the application of TMS.

Brainstem

The higher brain top down control of physiology is mediated by the sympathetic and parasympathetic nervous systems in the brainstem, and the hypothalamus. The sympathetic nervous system arises in brainstem nuclei that project down into intermediolateral columns of

thoracolumbar The vertebral column, also known as the backbone or spine, is part of the axial skeleton. The vertebral column is the defining characteristic of a vertebrate in which the notochord (a flexible rod of uniform composition) found in all chordates ...

spinal cord neurons in spinal segments T1–L2. The parasympathetic nervous system in the motor nuclei of

cranial nerves Cranial nerves are the nerves that emerge directly from the brain (including the brainstem), of which there are conventionally considered twelve pairs. Cranial nerves relay information between the brain and parts of the body, primarily to and f ...

III, VII, IX, (control over the pupil and salivary glands) and X (vagus –many functions including immunity) and sacral spinal segments (gastrointestinal and urogenital systems). Another control occurs through top down control by the medial areas of the

prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA46, ...

. upon the

which has a nonnerve control of the body through

secretions of the

Immunity

The brain controls immunity both indirectly through HPA

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...

secretions from the pituitary, and by various direct innervations. * Antibodies. There is sympathetic innervation of the

thymus gland The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. ...

. Sympathetic control exists over

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

production, and the modulation of

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

concentrations. * Cellular immunity. An intact sympathetic nervous system is required to maintain full cellular immunoregulation as denervated mice do not produce and activate, for example,

splenic The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

suppressor T cells, or

thymic The thymus is a specialized primary Lymphatic system#Structure, lymphoid organ of the immune system. Within the thymus, T cell, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body ada ...

NKT cells. * Organ inflammation. Sympathetic innervation of various organs contacts macrophages and dendritic cells and can increase local inflammation including the kidney gut, the skin, and the

synovial joints A synovial joint, also known as diarthrosis, joins bones or cartilage with a fibrous joint capsule that is continuous with the periosteum of the joined bones, constitutes the outer boundary of a synovial cavity, and surrounds the bones' articulat ...

* Antiinflammation. The vagus nerve carries a parasympathetic

cholinergic Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word "choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cation. F ...

antiinflammatory pathway that reduces

proinflammatory cytokine An inflammatory cytokine or proinflammatory cytokine is a type of signaling molecule (a cytokine) that is secreted from immune cells like helper T cells (Th) and macrophages, and certain other cell types that promote inflammation. They include inte ...

s such as

TNF Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...

by spleen

macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

in the

red pulp The red pulp of the spleen is composed of connective tissue known also as the cords of Billroth and many splenic sinusoids that are engorged with blood, giving it a red color. Its primary function is to filter the blood of antigens, microorgani ...

and the

marginal zone The marginal zone is the region at the interface between the non-lymphoid red pulp and the lymphoid white-pulp of the spleen. (Some sources consider it to be the part of red pulp which borders on the white pulp, while other sources consider it to ...

and so the activation of

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

. This control is in part controlled by direct innervation of body organs such as the spleen. However, the existence of the parasympathetic antiinflammatory nerve pathway is controversial with one reviewer stating: “there is no evidence for an anti-inflammatory role of the efferent vagus nerve that is independent of the sympathetic nervous system.”

Metabolism

The

receives both sympathetic and parasympathetic nervous system innervation. * Plasma glucose levels. A vagus brain-liver axis exists that detects

lipids Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...

produced by the gut and acts to regulate

glucose homeostasis Blood sugar regulation is the process by which the levels of blood sugar, primarily glucose, are maintained by the body within a narrow range. This tight regulation is referred to as glucose homeostasis. Insulin, which lowers blood sugar, and ...

. *

Glycogenesis Glycogenesis is the process of glycogen synthesis, in which glucose molecules are added to chains of glycogen for storage. This process is activated during rest periods following the Cori cycle, in the liver, and also activated by insulin in re ...

. Vagal activation also controls

glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body. Glycogen functions as one o ...

synthesis in the liver. *

lipogenesis In biochemistry, lipogenesis is the conversion of fatty acids and glycerol into fats, or a metabolic process through which acetyl-CoA is converted to triglyceride for storage in fat. Lipogenesis encompasses both fatty acid and triglyceride syn ...

. Vagal activation also controls the generation of

. *

Insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...

. Vagal innervation of the

pancreas The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an end ...

controls the release of insulin release from its

beta cells Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are dimini ...

(and this is inhibited by norepinephrine released under sympathetic control from the

splanchnic nerve The splanchnic nerves are paired visceral nerves (nerves that contribute to the innervation of the internal organs), carrying fibers of the autonomic nervous system ( visceral efferent fibers) as well as sensory fibers from the organs ( visceral a ...

). *

Thyroid hormones File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4 rect 376 268 820 433 Thyroid-stimulating hormone rect 411 200 849 266 Thyrotropin-releasing hormone rect 297 168 502 200 Hypothalamus rect 66 216 386 25 ...

can control glucose production via the hypothalamus and its sympathetic and parasympathetic innervation of the liver.

Other

Thermogenesis Thermogenesis is the process of heat production in organisms. It occurs in all warm-blooded animals, and also in a few species of thermogenic plants such as the Eastern skunk cabbage, the Voodoo lily (''Sauromatum venosum''), and the giant wate ...

– this is controlled by the sympathetic nervous system starting in the dorsolateral

preoptic area The preoptic area is a region of the hypothalamus. MeSH classifies it as part of the anterior hypothalamus. TA lists four nuclei in this region, (medial, median, lateral, and periventricular). Functions The preoptic area is responsible for ther ...

of the

anterior hypothalamus The hypothalamus () is a part of the brain that contains a number of small Nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gl ...

via projections from the rostral raphe pallidus to the spinal

intermediolateral nucleus The intermediolateral nucleus (IML) is a region of grey matter found in one of the three grey columns of the spinal cord, the lateral grey column. This is Rexed lamina VII. The intermediolateral cell column exists at vertebral levels T1 – L3. ...

nonshivering thermogenesis by brown adipose tissue. *

Stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...

–

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...

and

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...

, the

stress hormone Stress hormones are secreted by endocrine glands to modify one's internal environment during times of stress. By performing various functions such as mobilizing energy sources, increasing heart rate, and downregulating metabolic processes which a ...

s, are released from nerve terminals in the

adrenal medulla The adrenal medulla ( la, medulla glandulae suprarenalis) is part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of chromaffin cel ...

in the kidney innervated from the sympathetic nervous system’s

. * Kidney function – the sympathetic nervous system projects to the

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

and controls

glomerular filtration rate Renal functions include maintaining an acid–base balance; regulating fluid balance; regulating sodium, potassium, and other electrolytes; clearing toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood p ...

and so

fluid balance Fluid balance is an aspect of the homeostasis of organisms in which the amount of water in the organism needs to be controlled, via osmoregulation and behavior, such that the concentrations of electrolytes (salts in solution) in the various body ...

, sodium reabsorption, and

Conditioning

The brains of animals can anticipatorily learn to control cell level physiology such as immunity through

. In this conditioning, a neutral

stimulus A stimulus is something that causes a physiological response. It may refer to: *Stimulation **Stimulus (physiology), something external that influences an activity **Stimulus (psychology), a concept in behaviorism and perception *Stimulus (economi ...

saccharin Saccharin (''aka'' saccharine, Sodium sacchari) is an artificial sweetener with effectively no nutritional value. It is about 550 times as sweet as sucrose but has a bitter or metallic aftertaste, especially at high concentrations. Saccharin is u ...

is paired in a drink with an agent,

cyclophosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...

, that produces an unconditioned response (

immunosuppression Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...

). After learning this pairing, the taste of saccharin by itself through neural top down control created immunosuppression, as a new conditioned response. This work was originally done on rats, however, the same conditioning can also occur in humans. The conditioned response happens in the brain with the ventromedial nucleus of the hypothalamus providing the output pathway to the immune system, the amygdala, the input of visceral information, and the insular cortex acquires and creates the conditioned response. The production of different components of the immune system can be controlled as conditioned responses: * Antibodies *IL-2 * B, CD8+ T cells and CD4+ naive and memory T cells, and granulocytes. Such conditioning in rats can last a year. Nonimmune functions can also be conditioned: *

Serum iron Serum iron is a medical laboratory test that measures the amount of circulating iron that is bound to transferrin (90%) and serum ferritin (10%). Clinicians order this laboratory test when they are concerned about iron deficiency, which can cause ...

levels * The level of

oxidative Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...

DNA damage DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...

Insulin secretion Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...

* Blood glucose levels

References

{{DEFAULTSORT:Neural top-down control of physiology Autonomic nervous system Homeostasis Neurophysiology