CH 2 Neurons and Glia Introduction Glia outnumber neurons by tenfold (about 100 billion neurons) Neurons sense changes

ges in the enviro and communicate these changes to other neurons and command the bodys responses to these sensations Glia or glial cells mostly insulate, support, and nourish neighboring neurons The Neuron Doctrine Most cells are .01-.05 mm in diameter to study, do histology the microscopic study of the structure of tissues by fixing tissues by immersing them in formaldehyde and cutting them in thin slices using microtome Can stain nuclei of all cells and also the clumps of material surrounding the nuclei of neurons these clumps are called Nissl bodies and the stain is Nissl stain o Distinguishes neurons and glia from each otherenables study of the arrangement (cytoarchitecture) of neurons in diff. parts of the brain o In fact is staining the Rough ER The Golgi Stain Golgi Stain - Soaking brain tissue in silver chromate solution results in small percentage of neurons becoming darkly colored in their entirety o Shows central region that contains the nucleus and numerous thin tubes radiating away from central region Swollen region around cell nucleus = cell body, soma, perikaryon Thin tubes radiating from soma = neurites, two types being dendrites and axons Axons extend long distances and there is usually only 1 from cell body act like wires that carry the output of the neurons Dendrites rarely extend more than 2mm act as antennae of neuron to receive incoming signals, or input Cajals Contribution First to argue that neurons are not continuous w/ 1 another and must communicate by contact, not continuity this idea that neurons adhered to the cell theory = neuron doctrine The Prototypical Neuron The inside of the neuron is separated from the outside by the limiting skin (neuronal membrane) which lies like a circus tent on an intricate internal scaffolding, giving each part of the cell its 3D appearance The Soma ~20 um in diameter Watery fluid inside = cytosol, salty, K+ rich soln Nucleus o 5-10 um across, contained w/i dbl membrane (nuclear envelope) perforated by pores 0.1 um across o Inside are chromosomes containing DNA, and thus the genes expressed by neuron By process of RNA splicing, introns are removed and remaining exons are fused together and read during transcription

Rough ER o Enclosed stacks of membrane dotted w/ ribosomes that measure 25 nm in diameter There are also free ribosomes, and some may appear to be attached to several others by a thread = polyribosomes (thread is single strand mRNA and the associated ribosomes are working on it to make multiple copies of the same protein) If protein molecules is destined to reside w/i cytosol of neuron, then the proteins mRNA transcript gravitates toward free ribosomes, but if it is destined to be inserted into membrane of cell or organelle, its synthesized on RER o Many more RER in neurons in part b/c of special membrane proteins unique to them Smooth ER & Golgi Apparatus o SER performs diff. functions in diff. locations if attached to RER, folds membranebound proteins to give unique 3D shape, if not, regulates internal substances like calcium o Golgi is site of extensive post-translational chemical processing of proteins Mitochondrion o ~1 um length o w/i outer memberan, multiple folds are inner membrane = cristae, w/i which is the matrix o site of cellular respiration, pulling in pyruvic acid (derived from sugars and digested proteins and fats) and oxygen the acid enters the Krebs cycle, providing energy in another series of rxns w/i the cristae called the e- transport chain, resulting in addition of phosphate to ADP ATP each exhalation of mitochondrion releases 17 ATP molecules per molecule acid The Neuronal Membrane ~5nm thick and studded w/ proteins In neurons, proteins composition of the membrane varies depending on whether it is in the soma, dendrites or axon The Cytoskeleton Gives neurons their characteristic shape (scaffolding) The bones of the cytoskeleton are the microtubules, microfilaments, and neurofilaments Microtubules o ~20nm diameters, are big and run longitudinally down neuritis o Appears as straight, thick-walled, hollow pipe, the wall of which is composed of smaller strands braided like rope around the hollow core, that consist of the protein tubulin. Process of joining small proteins to form long strand of tubulin is called polymerization and the strand is known as a polymer o MAPs microtubule-associated proteins that anchor them to one another and to other parts of the neuron Pathological changes in an axonal MAP, tau, are implicated in dementia that accompanies Alzheimers disease Microfilaments

o 5 nm diameter, about same thickness as cell membrane o Found throughout neurons, particularly in neuritis o Braids of 2 thin strands which are polymers of protein actin (which is also critically involved in mechanism of muscle contraction) o Actin microfilaments are constantly undergoing assembly and disassembly regulated by signals in the neuron Neurofilaments o 10 nm diameter, exist in all cells of body as intermediate filaments o Consists of multiple subunits organized like a chain of sausages, each subunit consisting of 3 protein strands woven together o The protein strands are coiled in tight, springlike configuration making the neurofilament structure mechanically much stronger than the other two The Axon Begins w/ region called axon hillock which tapers to form initial section of axon proper Different from soma in that no rough ER extends into axon and there are few if any free ribosomes. Also the protein composition of axon membrane is fundamentally diff. from that of soma membrane these structural diffs translate into functional distinctions no protein synthesis (must come from soma) and the proteins in the axonal membrane enable it to serve as telegraph wire to send info over great distances Can extend less than mm to over a meter and can branch (branches = axon collaterals) o Recurrent collaterals are axon collaterals that return to communicate to same cell Diameter ranges 1-25mm speed of electrical signal that sweeps down axon (nerve impulse) varies depending on diameter the thicker it is, the faster the impulse travels Axon Terminal o The end is called axon terminal or terminal bouton, appearing as swollen disk o Pt. of contact w/ dendrites of next neuron = synapse o Branches at ends of axons collectively known as terminal arbor o When neuron makes synaptic contact w/ other cell it innervates that call, providing innervation o Cytoplasm in terminal differs in that: Microtubules dont extend into it Terminal contains numerous synaptic vesicles (50nm diameter) Inside surgace of membrane facing synapse has dense covering proteins Numerous mitochondria, indicating high energy demand Synapse o Space b/w pre and post synaptic sides of neurons = synaptic cleft, and the info transfer at synapse from 1 to another = synaptic transmission o Electrical signal chemical signal (neurotransmitter) electrical signal Axoplasmic Transport o Axons cannot be sustained when separated from parent cell body degeneration of axons that occurs when they are cut = Wallerian degeneration, which occurs since transport of materials from soma to axon terminal is interrupted o Movement of materials down axon = axoplasmic transport

To test speed of transport, injected somata w/ radioactive amino acids, speed up to 1000mm per day o Material is in vesicles that walk down microtubules (legs provided by protein kinesin, process fueled by ATP) in direction of soma to terminal this direction is anterograde transport o Terminalsoma movement is retrograde transport, same mechanism aexcept protein is dynein Dendrites Dendrites of single neuron collectively = dendritic tree Covered w/ 1000s of synapses, and the membrane under it is full of specialized protein receptors Dendrites of some neurons covered w/ dendritic spines (discovered by Cajal) believed to isolate various chemical reactions triggered by some types of synaptic activation o Unusual changes ins pines shown to occur in brains of mentally retarded ppl Fewer spines and often were unusually long and thin; extent of changes well correlated w/ degree of retardation o Spine # also very sensitive to quality of enviro experienced during early development Stewards research suggests that synaptic transmission can actually direct local protein synthesis in some neurons Classifying Neurons Classification Based on Number of Neurites Single neurite = unipolar, two = bipolar, three or more = multipolar (most common) Classification Based on Dendrites In cerebral cortex, there are two broad classes stellate (star-shaped) and pyramidal Spiny vs. aspinous Based on Connections Neurons w/ neuritis in sensory surfaces of body = primary sensory neurons, or if acons form synapses w/ muscles and command movements = motor neurons Neurons communicating w/ just other neurons = interneurons (majority0 Based on Axon Length Golgi Type 1 projection neurons w/ long axons from one part of brain to another o pyramidal Golgi Type 2 short axons not extending beyond vicinity of cell body; local circuit neurons o stellate Based on Neurotransmitter motor neurons that command voluntary movements all release acetylcholine in their synapses and are thus classified as cholinergic Glia Astrocytes most numerous in brain, filling the spaces between neurons and are only 20nm away from neurons that they prolly influence whether neurite grows or retracts essential role is regulating chemical content of this extracellular space

o ex: they envelop synaptic junctions restricting spread of neurotransmitter molecules that have been released tightly control extracellular concentration of several substances that have potential to interfere w/ proper neuronal function like regulating conc. of potassium ions in extracellular fluid Myelinating Glia oligodendroglial (central nervous system) and Schwann cells (peripheral nervous system) provide layers of membrane to insulate axons myelin sheath interrupted periodically leaving short length where axonal membrane is exposed = node of Ranvier Other Non-Neuronal Cells ependymal cells provide lining of fluid-filled ventricles w/I brain and help direct cell migration during brain development microglia function as phagocytes to remove debris left by dead or degenerating neurons and glia IN CLASS Brain vs. Mind o Descartes was one of first ppl to come up w/ reflexive idea of behavior basic reflexes w/ nervous system to mediate these reflexes Picture of person touching fire, as result of stimulus, fluid comes down from brain through nerve, causing the foot to retract first physiological description for behavior Didnt believe that you could reduce these complex cognitive functions simply to the brain however, so gave dualist perspective - two types of substances (matter and soul/spirits) Only humans had souls, didnt develop until 8 years old, before which only reflexes guide behavior, past that your soul is in charge Behavior as result of the effects of a complex array of factors o Well be taking a neurophilosophical approach feelings, emotions, stress, sense of self, thoughts, comes from neurons working together in certain parts of the brain Behavior is determined its complex, with multitude of factors affecting behavior, but there is still no free will there is a mechanistic explanation for what determines behavior Does this mean ppl are culpable of terrible acts? Cell Theory o All living things (plants, animals, unicellular organisms) are made up of cells o The cell is the structural and functional unit of all living things o All cells come from pre-exisiting cells by division (spontaneous generation does not occur) o Cells contain hereditary information which is passed from cell to cell during division o All cells are basically the same in chemical composition o All energy synthesis and use occurs within cells (metabolism and biochemistry) Reticular Theory vs. Neuron Doctrine

o Reticular theory - brain is a synctium (mass of cytoplasm w/i cell membrane that contains multiple nuclei and is often result of cellular fusion) o Neuron doctrine: the cell (neuron) is an anatomical unit (in addition to glia) Golgi stain allowed crisp staining of nerve cells improvements in microscopic lenses better visualization of cells & processes. Golgi recognized that dendrites are separate processes that end freely and do not anastomose But Cajal saw that axons and their dendrites, also end separately brain is not a syncytium, but composed of fundamental units -neurons and glia Final proof of the neuron doctrine by electron microscopy in 1950s. Pyramidal neuron in hippocampus Golgi Stain

Basic Parts of a neuron