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Dr. Fields is Chief, Nervous System Development and Plasticity Section, National Institutes of Health, NICHD, Bethesda, Maryland. He is the author of The Other Brain: From Dementia to Schizophrenia, How New Discoveries About the Brain Are Revolutionizing Medicine and Science.
Thirty years after Albert Einstein died, sections of his brain were put under the microscope in an effort to understand his genius. Contrary to what researchers had expected, he had a typical number of neurons, but an extraordinary number of glia, a type of brain cell that had historically been viewed as having some housekeeping functions and serving as the "glue" holding the brain and its neurons together.
The discovery of Einstein's rich endowment of glia in the 1980s prompted many neuroscientists to revise their assumptions about the importance of glial cells to the brain.
Glia are nervous system cells that communicate by chemical signaling rather than by electrical impulses. Originally glia were considered connective tissue involved in neuronal support and neuroinflammation, but in the last decade it has become evident that all types of glia can sense functional activity in neurons and influence transmission of information in several ways. Glia are involved in nearly every aspect of brain function, including brain development, homeostasis, information processing, neurological disease and psychiatric illness.
In the Brain, Glia Predominate
Brain tissue is comprised of two unique types of cells: neurons, which are electrically excitable, and glia, which are not. Rudolf Virchow (1821-1902), a pathologist with a special interest in connective tissue, coined the name "nervenkitt" to describe these non-neuronal cells in 1858, meaning “nerve putty or cement” in German.(1) The English translation of the word became “neuroglia,” adopting the Greek root for “glue.”
Glia are far from inert interstitial brain cells. Some types of glia are involved in synaptic transmission, which implicates these glial cells in many aspects of learning, memory and other types of information processing; and in nervous system dysfunction, including neurological and psychological disorders. Other glia cells mediate immune function or form electrical insulation on nerve axons (myelin).(2)
Glia cannot generate action potentials, the electro-chemical signals that are the basis of neural communication. They lack the cellular structures identified with neurons, including axons, dendrites and synapses. Instead these cells exhibit a diverse range of structures consistent with their diverse functions.
It is now well established that glia use several types of chemical intercellular signals to communicate with each other and with neurons. Ions and other small molecules are spread from cell-to cell through gap junction channels coupling the cell membranes of adjacent glial cells, but glia also communicate by releasing signaling molecules.(3)(4)(5) This includes many of the same neurotransmitters that neurons use for synaptic transmission, as well as growth factors, cytokines and chemokines. These chemical messages are detected by membrane receptors on other glia and on neurons.(6) This kind of communication is more of a broadcast "wave" of neurochemical activity than the direct line connection neurons tend to use, and is shown in the video below.
Glia perform three general functions, and there are distinct categories of glia primarily associated with each of these activities.(7)
AstrocytesThe name for astrocytes refers to the multi-branched cytoskeleton of the cells, which resembles stars when revealed by traditional histological stains or by immunocytochemistry for GFAP (glial fibrillary acidic protein), which is diagnostic for astrocytes. When visualized with cytoplasmic or membrane stains, astrocytes are seen to have an extremely complicated morphology, with numerous fine busy cell processes that associate intricately with neurons and synapses.
Credit: NIH/National Instititute of Neurological Disorders and Stroke (NINDS)
Astrocytes provide physical support and nutrition to neurons and respond to neural injury. The function of providing nutritional support for neurons was first deduced from the close association of some astrocytes with small blood vessels. Astrocytes near blood vessels extend processes called "end feet" that surround blood vessels, and through which substances are transported between the bloodstream and neurons.
Astrocytes transport ions and neurotransmitters from the extracellular space surrounding neurons to maintain the proper levels of ions and neurotransmitters.(8) These functions are essential for maintaining the membrane potential of neurons that is necessary to fire electrical impulses and to communicate by synaptic transmission. Cellular coupling among populations of astrocytes via gap junction channels siphons away potassium ions released by electrically active axons, and disperses it through an astrocytic network for disposal into the bloodstream.(9) Astrocytes also provide metabolic support to neurons by delivering lactate and glucose.(10)
Astrocytes that are in close proximity to blood vessels regulate local blood flow in response to neural demand.(11)(12) Astrocytes sense compounds released from electrically active neurons, and in turn, release compounds that dilate or constrict blood vessels in the vicinity. This local regulation of blood flow to supply active neurons is the basis for functional brain imaging using fMRI (functional magnetic resonance imaging). The regulation of blood flow by astrocytes also implicates these cells in migraine and stroke.
Astrocytes are also implicated in neural communication and appear to play a role in certain neurological diseases. Astrocytes at synapses take up neurotransmitter released by neurons.(13)(8) They can also release neurotransmitters and other neuroactive substances to either facilitate or inhibit synaptic communication between neurons.(14)(4)(3) This enables astrocytes to respond to neuronal activity(15)(16) and implicates astrocytes in epilepsy and many other neurological conditions where excitability is excessive or depressed.(16) Astrocytes have recently been shown to control excitability in the brain, affecting such behaviors as sleep(17) and chronic pain.(18)
Astrocytes have been implicated in strengthening and weakening synaptic transmission in the hippocampus in conjunction with memory formation.(19)(20)(21) Both strengthening and weakening of synapses can be regulated by astrocytes in the hippocampus through the release of neurotransmitters, notably glutamate, ATP and D-serine, but also by the delivery of glucose to neurons and by the maintenance of normal concentrations of extracellular ions (notably potassium ions), and glutamate.
In addition to releasing neurotransmitters, astrocytes release many types of growth factors, cytokines and antioxidants that protect and stimulate the growth of neurons. Unfortunately,under pathological or disease conditions, astrocytes can release oxidizing compounds, neurotransmitters, inflammatory cytokines and other toxic substances that damage or kill neurons. These actions involve astrocytes in neurological disorders such as ALS, Parkinson's disease and Alzheimer's disease.