Neuroanatomy

Anatomy of the human brain.

Neuroanatomy is the study of the anatomy and organization of the nervous system. In contrast to animals with radial symmetry, whose nervous system consists of a distributed network of cells, animals with bilateral symmetry have segregated, defined nervous systems, and thus we can begin to speak of their neuroanatomy. In vertebrates, both the internal structure of the brain and spinal cord (together called the central nervous system, or CNS) and the routes of the nerves that connect to the rest of the body (known as the peripheral nervous system, or PNS) are extremely elaborate. The delineation of distinct structures and regions of the nervous system has been critical in investigating how it works. For example, much of what neuroscientists have learned comes from observing how damage or "lesions" to specific brain areas affects behavior or other neural functions.

History

The first known written record of a study of the anatomy of the human brain is the ancient Egyptian document the Edwin Smith Papyrus.^[1] The next major development in neuroanatomy was some thousand years later when the Greek Alcmaeon determined that the brain and not the heart ruled the body and that the senses were dependent on the brain.^[2]

After Alcmaeon’s findings, many scientists, philosophers, and physicians from around the world continued to contribute to the understanding of neuroanatomy, notably: Galen, Herophilus, Rhazes and Erasistratus. Herophilus and Erasistratus of Alexandria were perhaps the most influential Greek neuroscientists with their studies involving dissecting the brains.^[2] For several hundred years afterward, with the cultural taboo of dissection, no major progress occurred in neuroscience. However, Pope Sixtus IV effectively revitalized the study of neuroanatomy by altering the papal policy and allowing human dissection. This resulted in a boom of research in neuroanatomy by artists and scientists of the Renaissance.^[3]

In 1664, Thomas Willis, a physician and professor at Oxford University, coined the term neurology when he published his text Cerebri anatome which is considered the foundation of neuroanatomy.^[4] The next four hundred some years has produced a great deal of documentation and study of the neural systems.

Composition

At the tissue level, the nervous system is composed of neurons, glial cells, and extracellular matrix. Both neurons and glial cells come in many types (see, for example, the nervous system section of the list of distinct cell types in the adult human body). Neurons are the information-processing cells of the nervous system: they sense our environment, communicate with each other via electrical signals and synapses, and produce our thoughts and movements. Glial cells maintain homeostasis, produce myelin, and provide support and protection for the brain's neurons. Some glial cells (astrocytes) can even propagate intercellular calcium waves over long distances in response to stimulation, and release gliotransmitters in response to changes in calcium concentration. The extracellular matrix also provides support on the molecular level for the brain's cells.

At the organ level, the nervous system is composed of brain regions, such as the hippocampus in mammals or the mushroom bodies of the fruit fly.^[5] These regions are often modular and serve a particular role within the general pathways of the nervous system. For example, the hippocampus is critical for forming memories. The nervous system also contains nerves, which are bundles of fibers that originate from the brain and spinal cord, and branch repeatedly to innervate every part of the body. Nerves are made primarily of the axons of neurons, along with a variety of membranes that wrap around and segregate them into nerve fascicles.

The vertebrate nervous system is divided into the central and peripheral nervous systems. The central nervous system (CNS) consists of the brain and spinal cord, while the peripheral nervous system (PNS) is made up of all the nerves outside of the CNS that connect it to the rest of the body. The PNS is further subdivided into the somatic and autonomic nervous systems. The somatic nervous system is made up of "afferent" neurons, which bring sensory information from the sense organs to the CNS, and "efferent" neurons, which carry motor instructions out to the muscles. The autonomic nervous system also has two subdivisions, the sympathetic and the parasympathetic, which are important for regulating the body's basic internal organ functions such as heartbeat, breathing, digestion, etc.

Orientation in neuroanatomy

Para-sagittal MRI of the head in a patient with benign familial macrocephaly.

In anatomy in general and neuroanatomy in particular, several sets of terms are used to denote orientation and location (see Anatomical terms of location). The pairs of terms used most commonly in neuroanatomy are:

• Dorsal and ventral: dorsal refers to the top or upper side, and ventral to the bottom or lower side.
• Rostral and caudal: rostral refers to the front (towards the nose; remember, "rostral" rhymes with "nostril"!), and caudal to the back (towards the tail).
• Medial and lateral: medial is towards the middle, and lateral is towards the side (away from the middle).

Commonly used terms for planes of orientation or planes of section in neuroanatomy are "transverse", "coronal", and "sagittal".

• A transverse plane is parallel to the ground, such that it divides the body or brain into a dorsal and a ventral portion.
• A sagittal plane divides the body or brain into left and right portions, and thus moves along the medial-lateral axis (see the image above).
• A coronal plane is parallel to the face, and thus divides the body or brain into rostral (front) and caudal (back).

The directional terms "superior" and "inferior" and the "horizontal" plane are often used interchangeably with "dorsal", "ventral", and "transverse", and are equivalent in all animals other than humans. However, because humans walk on two legs, we have evolved a kink in our central nervous system, known as the cephalic flexure, which bends the rostral part of the CNS at a 90 degree angle to the caudal part, at the level of the brainstem. Thus, confusion can arise when using these terms; for example, a coronal section of the forebrain, say, just behind the eyes, is in a plane parallel to the face. But as it moves in the rostral direction, it rotates, such that a coronal section of the spinal cord is parallel to the ground. Similarly, one can say that the forebrain, the most rostral part of the CNS, is the most anterior part of the nervous system of a rat or a dog, but is the most superior part in a human.

Tools

Modern developments in neuroanatomy are directly correlated to the technologies used to perform research. Therefore it is necessary to discuss the various tools that are available. Many of the histological techniques used to study other tissues can be applied to the nervous system as well. However, there are some techniques that have been developed especially for the study of neuroanatomy:

1. The classic Golgi stain uses potassium dichromate and silver nitrate to stain neurons' dendrites and cell bodies in brown and black, allowing researchers to trace the paths of their thin processes in a slice of nervous tissue.
2. By expressing variable amounts of red, green, and blue fluorescent proteins in the brain, the so-called "brainbow" mutant mouse allows the combinatorial visualization of many different colors in neurons. This tags neurons with enough unique colors that they can often be distinguished from their neighbors with fluorescence microscopy, enabling researchers to map the local connections between neurons.
3. Nissl staining uses dyes to intensely stain the rough endoplasmic reticulum, which is abundant in neurons. This allows researchers to distinguish between different cell types (such as neurons and glia) in various regions of the nervous system.
4. Magnetic resonance imaging has been used extensively to investigate brain structure and function non-invasively in healthy human subjects.

Model systems

Aside from the human brain, there are many other animals whose brains and nervous systems have received extensive study as model systems, including mice, zebrafish,^[6] fruit fly,^[7] and a species of roundworm called C. elegans. Each of these has its own advantages and disadvantages as a model system. For example, the C. elegans nervous system is extremely stereotyped from one individual worm to the next. This has allowed researchers using electron microscopy to map the paths and connections of all of the approximately 300 neurons in this species. The fruit fly is widely studied in part because its genetics is very well understood and easily manipulated. The mouse is used because, as a mammal, its brain is more similar in structure to our own (e.g., it has a six-layered cortex, yet its genes can be easily modified and its reproductive cycle is relatively fast.

C. elegans

Nervous system of a generic bilaterian animal, in the form of a nerve cord with segmental enlargements, and a "brain" at the front

The brain is small and simple in some species, such as the nematode worm, where the body plan is quite simple: 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 nematode Caenorhabditis elegans has been studied because of its importance in genetics.^[8] In the early 1970s, Sydney Brenner chose it as a model system for studying the way that genes control development, including neuronal development. One advantage of working with this worm is that the nervous system of the hermaphrodite contains exactly 302 neurons, always in the same places, making identical synaptic connections in every worm.^[9] 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.^[10] 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.^[11]

Drosophila melanogaster

Drosophila melanogaster is a popular experimental animal because it is easily cultured en masse from the wild, has a short generation time, and mutant animals are readily obtainable.

Arthropods have a central brain with three divisions and large optical lobes behind each eye for visual processing. The brain of a fruit fly contains several million synapses, compared to at least 100 trillion in the human brain. Approximately two-thirds of the Drosophila brain is dedicated to visual processing.

Thomas Hunt Morgan started to work with Drosophila in 1906, and this work earned him the 1933 Nobel Prize in Medicine for identifying chromosomes as the vector of inheritance for genes. Because of the large array of tools available for studying Drosophila genetics, they have been a natural subject for studying the role of genes in the nervous system.^[12] The genome has been sequenced and published in 2000. About 75% of known human disease genes have a recognizable match in the genome of fruit flies. Drosophila is being used as a genetic model for several human neurological diseases including the neurodegenerative disorders Parkinson's, Huntington's, spinocerebellar ataxia and Alzheimer's disease. In spite of the large evolutionary distance between insects and mammals, many basic aspects of Drosophila neurogenetics have turned out to be relevant to humans. For instance, the first biological clock genes were identified by examining Drosophila mutants that showed disrupted daily activity cycles.^[13]

Mouse

Mouse mutants: Rab23 is an essential negative regulator of the mouse Sonic hedgehog signaling pathway.^[14] The first understanding of biological processes requiring the Rab23 gene came from 2 independent mouse mutations in the gene ^[15][16] and an epistasis analysis with mutations in the mouse shh gene.^[14] These studies showed that the gene is required for normal development of the brain and spinal cord and that the morphological defects seen in mutant embryos, such as failure to close dorsal regions of the neural tube during development, appeared secondary to expansion of ventral and reduction of dorsal identities in the developing neural tube. These same mutations implicated the RAB23 gene in development of digits and eyes. The mouse open brain (opb) and Sonic hedgehog (Shh) genes have opposing roles in neural patterning: opb is required for dorsal cell types and Shh is required for ventral cell types in the spinal cord.^[14] In human, a regulator of rab: RabGDI alpha has been implicated in non-specific X-linked mental retardation.

See also

Neurology Neuroscience

References

1. ^ Atta, H. M. "Edwin Smith Surgical Papyrus: The Oldest Known Surgical Treatise". American Surgeon, 1999, 65(12), 1190-1192.
2. ^ ^{a b} Rose, F., "Cerebral Localization in Antiquity". Journal of the History of the Neurosciences, 2009, 18(3), 239-247.
3. ^ Ginn, S. R., & Lorusso, L., "Brain, Mind, and Body: Interactions with Art in Renaissance Italy". Journal of the History of the Neurosciences, 2008, 17(3), 295-313.
4. ^ Neher, A., "Christopher Wren, Thomas Willis and the Depiction of the Brain and Nerves". Journal of Medical Humanities, 2009, 30(3), 191-200.
5. ^ http://web.neurobio.arizona.edu/Flybrain/html/atlas/structures/mushroom.html
6. ^ Wullimann, Mario F.; Rupp, Barbar;, Reichert, Heinrich (1996). Neuroanatomy of the zebrafish brain: a topological atlas. ISBN 3764351209. http://books.google.com/books?id=B5QVXvbOb1YC&pg=PA1&lpg=PA1&dq#v=onepage&q&f=false. 
7. ^ http://web.neurobio.arizona.edu/Flybrain/html/index.html
8. ^ "WormBook: The online review of C. elegans biology". http://www.wormbook.org. Retrieved 2011-10-14. 
9. ^ Hobert, O (2005). Specification of the nervous system. In The C. elegans Research Community. "Wormbook". WormBook: 1–19. doi:10.1895/wormbook.1.12.1. PMID 18050401. http://www.wormbook.org/chapters/www_specnervsys/specnervsys.html. 
10. ^ White, JG; Southgate, E; Thomson, JN; Brenner, S (1986). "The Structure of the Nervous System of the Nematode Caenorhabditis elegans". Phil. Trans. Roy. Soc. London (Biology) 314 (1165): 1–340. doi:10.1098/rstb.1986.0056. 
11. ^ Hodgkin, J (2001). "Caenorhabditis elegans". In Brenner S, Miller JH. Encyclopedia of Genetics. Elsevier. pp. 251–256. ISBN 9780122270802. 
12. ^ "Flybrain: An online atlas and database of the drosophila nervous system". http://flybrain.neurobio.arizona.edu. Retrieved 2011-10-14. 
13. ^ Konopka, RJ; Benzer, S (1971). "Clock Mutants of Drosophila melanogaster". Proc Nat Acad Sci U.S.A. 68 (9): 2112–6. doi:10.1073/pnas.68.9.2112. PMC 389363. PMID 5002428. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=389363. 
14. ^ ^{a b c} Eggenschwiler JT, Espinoza E, Anderson KV (July 2001). "Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway". Nature 412 (6843): 194–8. doi:10.1038/35084089. PMID 11449277. 
15. ^ Günther T, Struwe M, Aguzzi A, Schughart K (November 1994). "Open brain, a new mouse mutant with severe neural tube defects, shows altered gene expression patterns in the developing spinal cord". Development 120 (11): 3119–30. PMID 7720556. 
16. ^ Kasarskis A, Manova K, Anderson KV (June 1998). "A phenotype-based screen for embryonic lethal mutations in the mouse". Proc. Natl. Acad. Sci. U.S.A. 95 (13): 7485–90. doi:10.1073/pnas.95.13.7485. PMC 22659. PMID 9636176. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=22659. 

External links

• Neuroanatomy, an annual journal of clinical neuroanatomy
• Mouse, Rat, Primate and Human Brain Atlases (UCLA Center for Computational Biology)
• brainmaps.org: High-Resolution Neuroanatomically-Annotated Brain Atlases
• BrainInfo for Neuroanatomy
• High quality neuroanatomical visual glossary with several hundred entries
• Brain Gene Expression Map, mouse gene expression neuroanatomical resource from St. Jude Children's Research Hospital
• Brain Architecture Management System, several atlases of brain anatomy
• White Matter Atlas, Diffusion Tensor Imaging Atlas of the Brain's White Matter Tracts