Brain (1)

This article is about the brains of all types of animals, including humans. For information specific to the human brain, see Human brain. For other uses, see Brain (disambiguation).

The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few invertebrates such as sponges, jellyfish, adult sea squirts and starfish do not have one, even if diffuse neural tissue is present. It is located in the head, usually close to the primary sensory organs for such senses as vision, hearing, balance, taste, and smell. The brain of a vertebrate is the most complex organ of its body. In a typical human the cerebral cortex (the largest part) is estimated to contain 15–33 billion neurons,[1] each connected by synapses to several thousand other neurons. These neurons communicate with one another by means of long protoplasmic fibers called axons, which carry trains of signal pulses called action potentials to distant parts of the brain or body targeting specific recipient cells.

Physiologically, the function of the brain is to exert centralized control over the other organs of the body. The brain acts on the rest of the body both by generating patterns of muscle activity and by driving secretion of chemicals called hormones. This centralized control allows rapid and coordinated responses to changes in the environment. Some basic types of responsiveness such as reflexes can be mediated by the spinal cord or peripheral ganglia, but sophisticated purposeful control of behavior based on complex sensory input requires the information-integrating capabilities of a centralized brain.

From a philosophical point of view, what makes the brain special in comparison to other organs is that it forms the physical structure that generates the mind. As Hippocrates put it: "Men ought to know that from nothing else but the brain come joys, delights, laughter and sports, and sorrows, griefs, despondency, and lamentations."[2] Through much of history, the mind was thought to be separate from the brain. Even for present-day neuroscience, the mechanisms by which brain activity gives rise to consciousness and thought remain very challenging to understand: despite rapid scientific progress, much about how the brain works remains a mystery. The operations of individual brain cells are now understood in considerable detail, but the way they cooperate in ensembles of millions has been very difficult to decipher. The most promising approaches treat the brain as a biological computer, very different in mechanism from electronic computers, but similar in the sense that it acquires information from the surrounding world, stores it, and processes it in a variety of ways.

This article compares the properties of brains across the entire range of animal species, with the greatest attention to vertebrates. It deals with the human brain insofar as it shares the properties of other brains. The ways in which the human brain differs from other brains are covered in the human brain article. Several topics that might be covered here are instead covered there because much more can be said about them in a human context. The most important is brain disease and the effects of brain damage, covered in the human brain article because the most common diseases of the human brain either do not show up in other species, or else manifest themselves in different ways.

Anatomy

The shape and size of the brains of different species vary greatly, and identifying common features is often difficult.[3] Nevertheless, there are a number of principles of brain architecture that apply across a wide range of species.[4] Some aspects of brain structure are common to almost the entire range of animals species;[5] others distinguish "advanced" brains from more primitive ones, or distinguish vertebrates from invertebrates.[3]

The simplest way to gain information about brain anatomy is by visual inspection, but many more sophisticated techniques have been developed. Brain tissue in its natural state is too soft to work with, but it can be hardened by immersion in alcohol or other fixatives, and then sliced apart for examination of the interior. Visually, the interior of the brain consists of areas of so-called grey matter, with a dark color, separated by areas of white matter, with a lighter color. Further information can be gained by staining slices of brain tissue with a variety of chemicals that bring out areas where specific types of molecules are present in high concentrations. It is also possible to examine the microstructure of brain tissue using a microscope, and to trace the pattern of connections from one brain area to another.[6]

Cellular structure

The brains of all species are composed primarily of two broad classes of cells: neurons and glial cells. Glial cells (also known as glia or neuroglia) come in several types, and perform a number of critical functions, including structural support, metabolic support, insulation, and guidance of development. Neurons, however, are usually considered the most important cells in the brain.[7]

The property that makes neurons unique is their ability to send signals to specific target cells over long distances.[8] They send these signals by means of an axon, which is a thin protoplasmic fiber that extends from the cell body and projects, usually with numerous branches, to other areas, sometimes nearby, sometimes in distant parts of the brain or body. The length of an axon can be extraordinary: for example, if a pyramidal cell of the cerebral cortex were magnified so that its cell body became the size of a human body, its axon, equally magnified, would become a cable a few centimeters in diameter, extending more than a kilometer.[9] These axons transmit signals in the form of electrochemical pulses called action potentials, which last less than a thousandth of a second and travel along the axon at speeds of 1–100 meters per second. Some neurons emit action potentials constantly, at rates of 10–100 per second, usually in irregular patterns; other neurons are quiet most of the time, but occasionally emit a burst of action potentials.[10]

Axons transmit signals to other neurons by means of specialized junctions called synapses. A single axon may make as many as several thousand synaptic connections with other cells.[11] When an action potential, traveling along an axon, arrives at a synapse, it causes a chemical called a neurotransmitter to be released. The neurotransmitter binds to receptor molecules in the membrane of the target cell.[12]

Synapses are the key functional elements of the brain.[13] The essential function of the brain is cell-to-cell communication, and synapses are the points at which communication occurs. The human brain has been estimated to contain approximately 100 trillion synapses;[14] even the brain of a fruit fly contains several million.[15] The functions of these synapses are very diverse: some are excitatory (excite the target cell); others are inhibitory; others work by activating second messenger systems that change the internal chemistry of their target cells in complex ways.[13] A large fraction of synapses are dynamically modifiable; that is, they are capable of changing strength in a way that is controlled by the patterns of signals that pass through them. It is widely believed that activity-dependent modification of synapses is the brain's primary mechanism for learning and memory.[13]

Most of the space in the brain is taken up by axons, which are often bundled together in what are called nerve fiber tracts. Many axons are wrapped in thick sheaths of a fatty substance called myelin, which serves to greatly increase the speed of signal propagation. Myelin is white, so parts of the brain filled exclusively with nerve fibers appear as light-colored white matter, in contrast to the darker-colored grey matter that marks areas with high densities of neuron cell bodies.[16]

Evolution

The generic bilaterian nervous system

Except for a few primitive types such as sponges (which have no nervous system[17]) and cnidarians (which have a nervous system consisting of a diffuse nerve net[17]), all living multicellular animals are bilaterians, meaning animals with a bilaterally symmetric body shape (that is, left and right sides that are approximate mirror images of each other).[18] All bilaterians are thought to have descended from a common ancestor that appeared early in the Cambrian period, 550–600 million years ago, and it has been hypothesized that this common ancestor had the shape of a simple tubeworm with a segmented body.[18] At a schematic level, that basic worm-shape continues to be reflected in the body and nervous system architecture of all modern bilaterians, including vertebrates.[19] The fundamental bilateral body form is a tube with a hollow gut cavity running from the mouth to the anus, and a nerve cord with an enlargement (a ganglion) for each body segment, with an especially large ganglion at the front, called the brain. The brain is small and simple in some species, such as nematode worms; in other species, including vertebrates, it is the most complex organ in the body.[3] Some types of worms, such as leeches, also have an enlarged ganglion at the back end of the nerve cord, known as a "tail brain".[20]

There are a few types of existing bilaterians that lack a recognizable brain, including echinoderms, tunicates, and a group of primitive flatworms called Acoelomorpha. It has not been definitively established whether the existence of these brainless species indicates that the earliest bilaterians lacked a brain, or whether their ancestors evolved in a way that led to the disappearance of a previously existing brain structure.[21]

Invertebrates

This category includes arthropods, molluscs, and numerous types of worms. The diversity of invertebrate body plans is matched by an equal diversity in brain structures.[22]

Two groups of invertebrates have notably complex brains: arthropods (insects, crustaceans, arachnids, and others), and cephalopods (octopuses, squids, and similar molluscs).[23] The brains of arthropods and cephalopods arise from twin parallel nerve cords that extend through the body of the animal. Arthropods have a central brain with three divisions and large optical lobes behind each eye for visual processing.[23] Cephalopods such as the octopus and squid have the largest brains of any  invertebrates.[24]

There are several invertebrate species whose brains have been studied intensively because they have properties that make them convenient for experimental work:

Fruit flies (Drosophila), because of the large array of techniques available for studying their genetics, have been a natural subject for studying the role of genes in brain development.[25] In spite of the large evolutionary distance between insects and mammals, many aspects of Drosophila neurogenetics have turned out to be relevant to humans. The first biological clock genes, for example, were identified by examining Drosophila mutants that showed disrupted daily activity cycles.[26] A search in the genomes of vertebrates turned up a set of analogous genes, which were found to play similar roles in the mouse biological clock—and therefore almost certainly in the human biological clock as well.[27]

The nematode worm Caenorhabditis elegans, like Drosophila, has been studied largely because of its importance in genetics.[28] In the early 1970s, Sydney Brenner chose it as a model system for studying the way that genes control development. One of the advantages of working with this worm is that the body plan is very stereotyped: the nervous system of the hermaphrodite morph contains exactly 302 neurons, always in the same places, making identical synaptic connections in every worm.[29] Brenner's team sliced worms into thousands of ultrathin sections and photographed every section under an electron microscope, then visually matched fibers from section to section, to map out every neuron and synapse in the entire body.[30] Nothing approaching this level of detail is available for any other organism, and the information has been used to enable a multitude of studies that would not have been possible without it.[31]

The sea slug Aplysia was chosen by Nobel Prize-winning neurophysiologist Eric Kandel as a model for studying the cellular basis of learning and memory, because of the simplicity and accessibility of its nervous system, and it has been examined in hundreds of experiments.[32]

Vertebrates

The first vertebrates appeared over 500 million years ago (Mya), during the Cambrian period, and may have resembled the modern hagfish in form.[33] Sharks appeared about 450 Mya, amphibians about 400 Mya, reptiles about 350 Mya, and mammals about 200 Mya. No modern species should be described as more "primitive" than others, strictly speaking, since each has an equally long evolutionary history—but the brains of modern hagfishes, lampreys, sharks, amphibians, reptiles, and mammals show a gradient of size and complexity that roughly follows the evolutionary sequence. All of these brains contain the same set of basic anatomical components, but many are rudimentary in the hagfish, whereas in mammals the foremost part (the telencephalon) is greatly elaborated and expanded.[34]

Brains are most simply compared in terms of their size. The relationship between brain size, body size and other variables has been studied across a wide range of vertebrate species. As a rule, brain size increases with body size, but not in a simple linear proportion. In general, smaller animals tend to have larger brains, measured as a fraction of body size: the animal with the largest brain-size-to-body-size ratio is the hummingbird. For mammals, the relationship between brain volume and body mass essentially follows a power law with an exponent of about 0.75.[35] This formula describes the central tendency, but every family of mammals departs from it to some degree, in a way that reflects in part the complexity of their behavior. For example, primates have brains 5 to 10 times larger than the formula predicts. Predators tend to have larger brains than their prey, relative to body size.[36]

All vertebrate brains share a common underlying form, which appears most clearly during early stages of embryonic development. In its earliest form, the brain appears as three swellings at the front end of the neural tube; these swellings eventually become the forebrain, midbrain, and hindbrain (the prosencephalon, mesencephalon, and rhombencephalon, respectively). At the earliest stages of brain development, the three areas are roughly equal in size. In many classes of vertebrates, such as fish and amphibians, the three parts remain similar in size in the adult, but in mammals the forebrain becomes much larger than the other parts, and the midbrain becomes very small.[37]

The brains of vertebrates are made of very soft tissue.[38] Living brain tissue is pinkish on the outside and mostly white on the inside, with subtle variations in color. Vertebrate brains are surrounded by a system of connective tissue membranes called meninges that separate the skull from the brain. Blood vessels enter the central nervous system through holes in the meningeal layers. The cells in the blood vessel walls are joined tightly to one another, forming the so-called blood–brain barrier, which protects the brain from toxins that might enter through the bloodstream.[39]

Neuroanatomists usually divide the vertebrate brain into six main regions: the telencephalon (cerebral hemispheres), diencephalon (thalamus and hypothalamus), mesencephalon (midbrain), cerebellum, pons, and medulla oblongata. Each of these areas has a complex internal structure. Some parts, such as the cerebral cortex and cerebellum, consist of layers that are folded or convoluted to fit within the available space. Other parts, such as the thalamus and hypothalamus, consist of clusters of many small nuclei. Thousands of distinguishable areas can be identified within the vertebrate brain based on fine distinctions of neural structure, chemistry, and connectivity.[38]

Although the same basic components are present in all vertebrate brains, some branches of vertebrate evolution have led to substantial distortions of brain geometry, especially in the forebrain area. The brain of a shark shows the basic components in a straightforward way, but in teleost fishes (the great majority of existing fish species), the forebrain has become "everted", like a sock turned inside out. In birds, there are also major changes in forebrain structure.[40] These distortions can make it difficult to match brain components from one species with those of another species.[41]

Here is a list of some of the most important vertebrate brain components, along with a brief description of their functions as currently understood:

The medulla, along with the spinal cord, contains many small nuclei involved in a wide variety of sensory and motor functions.[42]

The pons lies in the brainstem directly above the medulla. Among other things, it contains nuclei that control sleep, respiration, swallowing, bladder function, equilibrium, eye movement, facial expressions, and posture.[43]

The hypothalamus is a small region at the base of the forebrain, whose complexity and importance belies its size. It is composed of numerous small nuclei, each with distinct connections and neurochemistry. The hypothalamus regulates sleep and wake cycles, eating and drinking, hormone release, and many other critical biological functions.[44]

The thalamus is another collection of nuclei with diverse functions. Some are involved in relaying information to and from the cerebral hemispheres. Others are involved in motivation. The subthalamic area (zona incerta) seems to contain action-generating systems for several types of "consummatory" behaviors, including eating, drinking, defecation, and copulation.[45]

The cerebellum modulates the outputs of other brain systems to make them precise. Removal of the cerebellum does not prevent an animal from doing anything in particular, but it makes actions hesitant and clumsy. This precision is not built-in, but learned by trial and error. Learning how to ride a bicycle is an example of a type of neural plasticity that may take place largely within the cerebellum.[46]

The optic tectum allows actions to be directed toward points in space, most commonly in response to visual input. In mammals it is usually referred to as the superior colliculus, and its best-studied function is to direct eye movements. It also directs reaching movements and other object-directed actions. It receives strong visual inputs, but also inputs from other senses that are useful in directing actions, such as auditory input in owls and input from the thermosensitive pit organs in snakes. In some fishes, such as lampreys, this region is the largest part of the brain.[47] The superior colliculus is part of the midbrain.

The pallium is a layer of gray matter that lies on the surface of the forebrain. In reptiles and mammals, it is called the cerebral cortex. Multiple functions involve the pallium, including olfaction and spatial memory. In mammals, where it becomes so large as to dominate the brain, it takes over functions from many other brain areas. In many mammals, the cerebral cortex consists of folded bulges called gyri that create deep furrows or fissures called sulci. The folds increase the surface area of the cortex and therefore increase the amount of gray matter and the amount of information that can be processed.[48]

The hippocampus, strictly speaking, is found only in mammals. However, the area it derives from, the medial pallium, has counterparts in all vertebrates. There is evidence that this part of the brain is involved in spatial memory and navigation in fishes, birds, reptiles, and mammals.[49]

The basal ganglia are a group of interconnected structures in the forebrain. The primary function of the basal ganglia appears to be action selection: they send inhibitory signals to all parts of the brain that can generate motor behaviors, and in the right circumstances can release the inhibition, so that the action-generating systems are able to execute their actions. Reward and punishment exert their most important neural effects by altering connections within the basal ganglia.[50]

The olfactory bulb is a special structure that processes olfactory sensory signals and sends its output to the olfactory part of the pallium. It is a major brain component in many vertebrates, but is greatly reduced in primates.[51]

Mammals

The most obvious difference between the brains of mammals and other vertebrates is in terms of size. On average, a mammal has a brain roughly twice as large as that of a bird of the same body size, and ten times as large as that of a reptile of the same body size.[52]

Size, however, is not the only difference: there are also substantial differences in shape. The hindbrain and midbrain of mammals are generally similar to those of other vertebrates, but dramatic differences appear in the forebrain, which is greatly enlarged and also altered in structure.[53] The cerebral cortex is the part of the brain that most strongly distinguishes mammals. In non-mammalian vertebrates, the surface of the cerebrum is lined with a comparatively simple three-layered structure called the pallium. In mammals, the pallium evolves into a complex six-layered structure called neocortex or isocortex.[54] Several areas at the edge of the neocortex, including the hippocampus and amygdala, are also much more extensively developed in mammals than in other vertebrates.[53]

The elaboration of the cerebral cortex carries with it changes to other brain areas. The superior colliculus, which plays a major role in visual control of behavior in most vertebrates, shrinks to a small size in mammals, and many of its functions are taken over by visual areas of the cerebral cortex.[52] The cerebellum of mammals contains a large portion (the neocerebellum) dedicated to supporting the cerebral cortex, which has no counterpart in other vertebrates.[55]

Primates

The brains of humans and other primates contain the same structures as the brains of other mammals, but are generally larger in proportion to body size.[59] The most widely accepted way of comparing brain sizes across species is the so-called encephalization quotient (EQ), which takes into account the nonlinearity of the brain-to-body relationship.[56] Humans have an average EQ in the 7-to-8 range, while most other primates have an EQ in the 2-to-3 range. Dolphins have values higher than those of primates other than humans,[57] but nearly all other mammals have EQ values that are substantially lower.

Most of the enlargement of the primate brain comes from a massive expansion of the cerebral cortex, especially the prefrontal cortex and the parts of the cortex involved in vision.[60] The visual processing network of primates includes at least 30 distinguishable brain areas, with a complex web of interconnections. It has been estimated that visual processing areas occupy more than half of the total surface of the primate neocortex.[61] The prefrontal cortex carries out functions that include planning, working memory, motivation, attention, and executive control. It takes up a much larger proportion of the brain for primates than for other species, and an especially large fraction of the human brain.[62]