January 16, 2011 Chapter 2: Neurons and Glia Introduction y The specialized functions of cells and how they

interact determine the functions of organs y Glia outnumber neurons by tenfold y Neurons are most important cells for the unique functions of the brain o Neurons sense changes in environment, communicate these changes to other neurons and command bodys responses to these sensations y Glia are thought to contribute to brain function mainly by insulating, supporting, and nourishing neighboring neurons The Neuron Doctrine y Histology: the microscopic study of the structure of tissues y Nissl stain was developed by Franz Nissl o Distinguishes neurons and glia from one another o Enables histologists to study the arrangement, or cytoarchitecture, of neurons in different parts of the brain The Golgi Stain y Golgi stain: silver chromate solution; produces a small percentage of neurons to become darkly colored y Revealed that the neuronal cell body, the region of the neuron around the nucleus that is shown w. Nissl stain, is actually only a small fraction of total structure of neuron y Neurons have at least two distinguishable parts: a central region that contains the cell nucleus, and numerous thin tubes that radiate away from the central region y The swollen region containing the cell nucleus has several names that are used interchangeably: cell body, soma, perikaryon y The thin tubes that radiate away from soma are called neuritis and are of two types: axons and dendrites y Cell body usually gives rise to a single axon o Axon is of uniform diameter throughout its length, and if it branches, generally extend at right angles o Travel over great distances (meter or more), act like wires that carry the output of the neurons y Dendrites rarely extend more than 2 mm in length o b/c dendrites come in contact w. many axons, they must act as the antennae of the neuron to receive incoming signals, or input Cajals Contribution y Golgi championed the view that the neurites of diff cells are fused together to form a continuous reticulum, or network y Cajal argued that neurites of diff neurons are not continuous w. one another and must communicate by contact, not continuity y Neuron doctrine: the idea that the neuron adhered to the cell theory y Neurites of diff neurons are not continuous w. one another

The Prototypical Neuron y Inside of neuron is separated from outside by neuronal membrane The Soma y Cell body of typical neuron is about 20 micrometers in diameter y Cytosol: water fluid inside the cell is a salty, potassium-rich solution that is separated from the outside by the neuronal membrane y Within soma are many membrane-enclosed structures called organelles y Neuron contains nucleus, rough ER, smooth ER, Golgi apparatus, and mitochondria y Cytoplasm: everything contained within the confines of the cell membrane, including organelles but excluding nucleus The nucleus y Nucleus of cell is spherical, centrally located and about 5-10 micrometers across o Contained within nuclear envelope that is perforated by pores that measure about 0.1 micrometers across y Within nucleus are chromosomes, which contain genetic material DNA o DNA in neurons is same as DNA in other cells o What distinguishes a neuron from a liver cell are specific parts of DNA that are used to assemble the cell genes y Reading of the DNA is known as gene expression y Final product of gene expression is synthesis of proteins, which perform many diff functions and bestow upon neurons virtually all of their unique characteristics y Protein synthesis occurs in cytoplasm y Messenger ribonucleic acid (mRNA) has function of carrying genetic message to sites of protein synthesis in cytoplasm b/c DNA never leaves nucleus y Transcription: process of assembling a piece of mRNA that contains the info of a gene o Protein-coding genes are flanked by stretches of DNA that are not used to encode proteins but are important for regulating transcription y At one end of gene is the promoter, the region where the RNA-synthesizing enzyme, RNA polymerase, binds to initiate transcription o Binding of the polymerase to the promoter is tightly regulated by other proteins called transcription factors y At other end is sequence of DNA called the terminator that the RNA polymerase recognizes as the end point for transcription y There are interspersed regions that cannot be used to code for protein called introns o Coding sequences are exons y Initial transcripts contain both introns and exons, but after RNA splicing, the introns are removed and the remaining exons are fused together y mRNA transcripts emerge from nucleus via pores in nuclear envelope and travel to sites of protein synthesis elsewhere in the neuron o At these sites, a protein molecule is assembled much as the mRNA molecule was: by linking together many small molecules into a chain y Building blocks of protein are amino acids, of which there are 20 diff kinds y Assembling of proteins from amino acids under direction of the mRNA is translation y Central dogma: DNA RNA protein y Molecular neurobiology

Rough endoplasmic reticulum y Enclosed stacks of membrane dotted w. dense globular structures called ribosomes, which measure about 25 nm in diameter o These stacks are called rough endoplasmic reticulum y Rough ER abounds in neurons, far more than in glia or most other non-neuronal cells (aka Nissl bodies) y Major site of protein synthesis in neurons o RNA transcripts bind to the ribosomes, and ribosomes translate the instructions contained in the mRNA to assemble a protein molecule y Ribosomes take raw material in form of amino acids and manufacture proteins using the blueprint provided by the mRNA y Several free ribosomes may appear to be attached by a thread polyribosomes o Thread is a single strand of mRNA, and the associated ribosomes are working on it to make multiple copies of the same protein y If it is destined to reside within the cytosol of the neuron, then the proteins mRNA transcript shuns the ribosomes of the rough ER and gravitates toward the free ribosomes y If protein is destined to be inserted into the membrane of the cell or an organelle, then it is synthesized on the rough ER y Neurons are well endowed w. rough ER b/c special membrane proteins are what give these cells their remarkable info-processing abilities Smooth ER and Golgi apparatus y Some smoothER is continuous w. rough ER and is believed to be a site where the proteins that jut out from the membrane are carefully folded, giving them their 3D structure o Other types regulate internal concentrations of substances such as calcium  Prominent in muscle cells called sarcoplasmic reticulum y Golgi apparatus is the stack of membrane-enclosed disks in soma that lies farthest from the nucleus o Site of extensive post translational chemical processing of proteins o Sorting of certain proteins that are destined for delivery to diff parts of the neuron, such as the axon and the dendrites The mitochondrion y In neurons, mitochondrion measures about 1 micrometer in length o Multiple folds of inner membrane called cristae o B/t cristae is an inner space called matrix y Site of cellular respiration o Pulls inside pyruvic acid and oxygen, both floating in the cytosol o Within inner compartment of the microchondrion, pyruvic acid enters into complex series of biochemical reactions called Krebs cycle  Products provide energy that, in another series of rxns within cristae (ETC), results in the addition of phosphate to ADP, yielding ATP cells energy source y Chemical energy in ATP is used to fuel most of the biochemical reactions of the neuron The Neuronal Membrane y Neuronalmembrane serves as barrier to enclose the cytoplasm inside the neuron and to exclude certain substances that float in the fluid that bathes the neuron

About 5 nm thick and studded w. proteins o Some of these proteins pump substances from inside to outside o Others form pores that regulate which substances can gain access to the inside of the neuron y Protein composition of the membrane varies depending on whether it is in the soma, the dendrites, or the axon The Cytoskeleton y Cytoskeleton gives the neuron its characteristic shape y Bones of the cytoskeleton are the microtubules, microfilaments, and neurofilaments Microtubules y Microtubules measure 20 nm in diameter and run longitudinally down neurites o Appears as a straight, thick-walled hollow pipe o The wall of pipe is composed of smaller strands that are braided like rope around the hollow core o Each of the smaller strands consists of the protein tubulin  Single tubulin molecule is small and globular; the strand consists of tubulins stuck together y The process of joining small proteins to form a long strand is called polymerization polymer y One class of proteins that participate in regulation of microtubule assembly and function are microtubule-associated proteins (MAPs) o MAPs also anchor the microtubules to one another and to other parts of the neuron Microfilaments y Measure only 5 nm in diameter, microfilaments are about same thickness as cell membrane y Particularly numerous in the neurites y Braids of two thin strands, and the strands are polymers of the protein actin y Actin is one of the most abundant proteins in cells of all types, including neurons, and is believed to play a role in changing cell shape y Actin microfilaments are constantly undergoing assembly and disassembly process is regulated by signals in the neuron y Run longitudinally down core of the neurites y Anchored to the membrane by attachments w. a meshwork of fibrous proteins that line the inside of the membrane like a spider web Neurofilaments y Diameter of 10 nm, neurofilaments are intermediate in size b/t microtubules and microfilaments y Equivalent to intermediate filaments of body cells; specifically named for neurons y Most closely resemble the bones and ligaments of the skeleton y Consists of multiple subunits that are organized like a chain of sausages o The internal structure of each subunit consists of three protein strands woven together y

 The Axon y Axon begins w. region called axon hillock, which tapers to form the initial segment of the axon proper y Two features that distinguish axon from soma o No rough ER extends into axon; few if any free ribosomes o The protein composition of the axon membrane is fundamentally diff from that of the soma membrane y B/c there are no ribosomes, there is no protein synthesis in the axon o All proteins in axon must originate in the soma y Axons often branch, and these branches are called axon collaterals o Sometimes, an axon collateral can return to communicate w. same cell that gave rise to axon or w. dendrites of neighboring cells recurrent collaterals y Speed of electrical signal that sweeps down axon nerve impulse varies depending on axonal diameter o Thicker the axon, the faster the impulse travels The axon terminal y Beginning axon hillock; middle axon proper; end axonterminalor axon bouton y The terminal is a site where the axon comes in contact w. other neurons and passes info on to them o The point of contact is called synapse y Sometimes axons have many branches at their ends, and each branch forms a synapse on dendrites or cell bodies in same region o These branches are collectively called the terminal arbor y Sometimes axons form synapses at swollen regions along their length and then continue to terminate elsewhere o Boutons en passant (buttons in passing) y In either case, when a neuron makes synaptic contact w. another cell, it is said to innervate that cell, or provide innervation y Cytoplasm of axon terminal differs from that of axon in several ways o Microtubules do not extend into the terminal o The terminal contains numerous small bubbles of membrane, called synaptic vesicles, that measure about 50 nm in diameter o The inside surface of the membrane that faces the synapse has a particularly dense covering of proteins o It has numerous mitochondria, indicating a high energy demand The synapse y Two sides: presynaptic and postsynaptic y Presynaptic side generally consists of an axon terminal, while the postsynaptic side may be the dendrite or soma of another neuron y Space b/t the presynaptic and postsynaptic membranes is called synaptic cleft y Transfer of info at synapse from one neuron to another is called synaptic transmission

nlike microfilaments and microtubules, these strands consist of individual long protein molecules, each of which is coiled in a tight, springlike configuration This structure makes neurofilaments mechanically very strong

At most synapses, info in form of electrical impulses traveling down the axon is converted in the terminal into a chemical signal that crosses the synaptic cleft o On postsynaptic membrane, this chemical signal is converted again into an electrical one o Chemical signal is called a neurotransmitter, and it is stored in and released from the synaptic vesicles within the terminal y Electrical to chemical to electrical transformation of info Axoplasmic transport y Axons cannot be sustained when separated from their parent cell body Wallerian degeneration y Wallerian degeneration occurs b/c the normal flow of materials from the soma to the axon terminal is interrupted y The movement of material down the axon is called axoplasmic transport o Material is enclosed within vesicles, which then walk down the microtubules of the axon  The legs are provided by a protein called kinesin, and process is fueled by ATP  Kinesin moves material only from soma to terminal movement of material in this direction is anterograde transport y Movement of material up the axon from terminal to soma is called retrograde transport o Process is believed to provide signals to soma about changes in the metabolic needs of the axon terminal  The legs are provided by diff protein dynein Dendrites y Dendrites of a single neuron are collectively called a dendritic tree o Each branch is called a dendritic branch y B/c dendrites function as antennae of neuron, they are covered w. thousands of synapses o The dendritic membrane under the postsynaptic membrane has many specialized protein molecules called receptors that detect neurotransmitters in the synaptic cleft y For most part, cytoplasm resembles that of axons o Filled w. cytoskeletal elements and mitochondria y Steward found one difference polyribosomes can be observed in dendrites, often right under spines y Classifying Neurons Classification Based on the Number of Neurites y Neurons can be classified according to total number of neurites (axons and dendrites) that extend from the soma o A neuron that has single neurite is said to be unipolar o Two is bipolar; three or more is multipolar y Most neurons in the brain are multipolar Classification Based on Dendrites y Classification is often unique to a particular part of the brain o The cerebral cortex has two broad classes: stellate cells (star shaped) and pyramidal cells (pyramid shaped)

Another simple way is whether their dendrites have spines o If yes, they are called spiny; if no, then aspinous Classification Based on Connections y Info is delivered to nervous system by neurons that have neurites in the sensory surfaces of the body, such as the skin and the retina of the eye primary sensory neurons y Other neurons have axons that form synapses w. the muscles and command movements motor neurons y But most neurons in nervous system form connections only w. other neurons interneurons Classification Based on Axon Length y Some neurons have long axons that extend from one part of the brain to the other Golgi type I neurons or projection neurons y Other neurons have short axons that do not extend beyond the vicinity of the cell body Golgi type II neurons or local circuit neurons y E.g. in cerebral cortex, pyramidal cells usually have long axons that extend to other parts of the brain and are therefore Golgi type I neurons y Stellate cells have axons that never extend beyond the cerebral cortex and are therefore Golgi type II neurons Classification Based on Neurotransmitter y Motor neurons that command voluntary movements all release the neurotransmitter acetylcholine at their synapses o Also classified as cholinergic, meaning that they use this particular transmitter y Glia y

Evidence indicates that glia contribute to brain function mainly by supporting neuronal functions Astrocytes y Astrocytes are most numerous glia in brain o Fill spaces b/t neurons o Probably influence whether a neurite can grow or retract y An essential role of astrocytes is regulating the chemical content of this extracellular space o E.g. astrocytes envelop synaptic junctions in the brain, thereby restricting the spread of neurotransmitter molecules that have been released o Astrocytes also have special proteins in their membranes that actively remove many neurotransmitters from the synaptic cleft o Astrocytic membranes also possess neurotransmitter receptors, that, like the receptors on neurons, can trigger electrical and biochemical events inside the glial cell y Also tightly control the extracellular concentration of several substances that have the potential to interfere w. proper neuronal function o E.g. regulate concentration of potassium ions in extracellular fluid Myelinating Glia y Primary function of oligodendroglial and Schwann cells provide layers of membrane that insulate axons y Wrapping called myelin, spirals around axons in the brain

Myelin sheath is interrupted periodically, leaving a short length where the axonal membrane is exposed, called node of Ranvier y Myelin serves to speed the propagation of nerve impulses down the axon y Oligodendroglia and Schwann cells differ in their location and some other characteristics o E.g. oligodendroglia are found only in central nervous system; Schwann cells found only in peripheral nervous system o One oligodendroglial cell will contribute myelin to several axons, while each Schwann cell myelinates only a single axon Other Non-Neuronal Cells y Special cells called ependymal cells provide the lining of fluid-filled ventricles within the brain, and they also play a role in directing cell migration during brain development y A class of cells called microglia function as phagocytes to remove debris left by dead or degenerating neurons and glia y