Saladin AP 10e Chap12 Nervous Tissue - PDF

Because learning changes everything. ® Chapter 12 Nervous Tissue ANATOMY & PHYSIOLOGY The Unity of Form and Function TENTH EDITION KENNETH S. SALADIN © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill L...

Because learning changes everything. ® Chapter 12 Nervous Tissue ANATOMY & PHYSIOLOGY The Unity of Form and Function TENTH EDITION KENNETH S. SALADIN © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC.  12.1 Overview of the Nervous System 1 Expected Learning Outcomes: Describe the overall function of the nervous system. Describe its major anatomical and functional subdivisions. © McGraw Hill, LLC 2  Overview of the Nervous System 2 Endocrine system and nervous system maintain internal coordination Endocrine system communicates by means of chemical messengers (hormones) secreted into to the blood Nervous system utilizes neurons (nerve cells) to send messages from cell to cell by electrical and chemical means; occurs in three steps: 1. It receives stimuli from external environment and transmits messages to central nervous system (CNS) 2. The CNS processes the information and determines response 3. CNS issues commands to muscle and gland cells to carry out response © McGraw Hill, LLC 3  Overview of the Nervous System 3 Nervous system has two major anatomical subdivisions: Central nervous system (CNS)— brain and spinal cord Peripheral nervous system (PNS)—nerves and ganglia Nerve—a bundle of nerve fibers (axons) wrapped in fibrous connective tissue Ganglion—a knot-like swelling in a nerve where neuron cell bodies of PNS are concentrated Access the text alternative for slide images. Figure 12.1 © McGraw Hill, LLC 4  Overview of the Nervous System 4 Functional divisions of peripheral nervous system: Peripheral nervous system is functionally divided into sensory and motor divisions, each with somatic and visceral subdivisions Sensory (afferent) division—carries signals from receptors (sense organs) to CNS Somatic sensory division—carries signals from receptors in the skin, muscles, bones, and joints Visceral sensory division—carries signals from the viscera (heart, lungs, stomach, and urinary bladder) © McGraw Hill, LLC 5  Overview of the Nervous System 5 Functional divisions of peripheral nervous system (continued): Motor (efferent) division—carries signals from CNS to effectors (glands and muscles that carry out the body’s response) Somatic motor division—carries signals to skeletal muscles; causes voluntary muscle contraction and automatic reflexes Visceral motor division (autonomic nervous system, ANS)— carries signals to glands, cardiac and smooth muscle; no voluntary control; responses called visceral reflexes Sympathetic division of ANS stimulates and prepares the body for action Parasympathetic division of ANS has a calming effect on the body An enteric plexus within digestive tract wall enables coordination and communication within digestive tract © McGraw Hill, LLC 6  Divisions of the Nervous System Access the text alternative for slide images. Figure 12.2 © McGraw Hill, LLC 7  12.2 Properties of Neurons Expected Learning Outcomes: Describe three functional properties found in all neurons. Define the three most basic functional categories of neurons. Identify the parts of a neuron. Describe four structural classes of neurons. Explain how neurons transport materials between the cell body and tips of the axon. © McGraw Hill, LLC 8  12.2a Universal Properties Three properties allow neurons to communicate with other cells: Excitability—ability to respond to stimuli Conductivity—produce electrical signals that are conducted to other cells Secretion—when signal reaches end of axon, the neuron secretes a neurotransmitter that stimulates the next cell © McGraw Hill, LLC 9  12.2b Functional Classes Three functional classes of neurons: Sensory (afferent) neurons—detect stimuli and transmit information about them toward the CNS Begin in every organ of body and terminate in CNS Interneurons—receive signals from other neurons, process this information, and make resulting “decisions” Lie entirely within CNS connecting motor and sensory pathways; most common functional type (about 90% of all neurons) Motor (efferent) neurons—send signals out to muscles and gland cells (the effectors) © McGraw Hill, LLC 10  The Three Functional Classes of Neurons Access the text alternative for slide images. Figure 12.3 © McGraw Hill, LLC 11  12.2c Structure of a Neuron 1 Principal components of a neuron: Cell body—also called neurosoma, soma, or perikaryon; contains nucleus and many organelles Mitochondria, lysosomes, Golgi complex, inclusions, rough ER Cytoskeleton contains microtubules, and neurofibrils (actin bundles) compartmentalize the rough ER into dark-staining chromatophilic substance No centrioles; mature neurons cannot undergo mitosis after adolescence Inclusions may be glycogen granules, lipid droplets, melanin, or lipofuscin (pigment resulting from degradation of organelles by lysosomes) © McGraw Hill, LLC 12  Structure of a Neuron 2 Principal components of a neuron (continued): Neurons can have many neurites (extensions) reaching out to other cells Dendrites—most numerous neurites, resemble branching of a tree; primary sites for receiving signals from other neurons Neurons can have one dendrite or thousands of dendrites Axon (nerve fiber)—long, cylindrical extension; relatively unbranched but may give off axon collaterals; specialized for rapid conduction of nerve signals Originates at axon hillock—mound on one side of cell body Contains axoplasm (its cytoplasm) and its membrane is the axolemma At its end, an axon branches profusely—the terminal arborization Each branch of arborization ends in a bulbous axon terminal (terminal bouton), which forms a synapse with next cell A neuron never has more than one axon; some neurons have none © McGraw Hill, LLC 13  General Structure of a Neuron 1 b: Ed Reschke Access the text alternative for slide images. Figure 12.4 © McGraw Hill, LLC 14  General Structure of a Neuron 2 Access the text alternative for slide images. Figure 12.4a © McGraw Hill, LLC 15  General Structure of a Neuron 3 Access the text alternative for slide images. Figure 12.4a © McGraw Hill, LLC 16  General Structure of a Neuron 4 b: Ed Reschke Figure 12.4b © McGraw Hill, LLC 17  General Structure of a Neuron 5 Figure 12.4c © McGraw Hill, LLC 18  General Structure of a Neuron 6 Access the text alternative for slide images. Figure 12.4d,e © McGraw Hill, LLC 19  Structure of a Neuron 3 Four structural classes of neurons, determined by number of cell processes extending from cell body: Multipolar neuron—one axon and multiple dendrites; most common type in body, most neurons in CNS Bipolar neuron—one axon and one dendrite; examples include olfactory cells, some neurons of retina, sensory neurons of ear Unipolar neuron—single process leading away from cell body, splits into peripheral process and central process Both processes comprise the axon; only short receptive endings of peripheral process are considered dendrites Anaxonic neuron—many dendrites but no axon; found in brain, retina, and adrenal gland © McGraw Hill, LLC 20  Structural Classes of Neurons 1 Access the text alternative for slide images. Figure 12.5a © McGraw Hill, LLC 21  Structural Classes of Neurons 2 Access the text alternative for slide images. Figure 12.5b © McGraw Hill, LLC 22  Structural Classes of Neurons 3 Access the text alternative for slide images. Figure 12.5c,d © McGraw Hill, LLC 23  12.2d Axonal Transport 1 Axonal transport—two-way passage of materials along an axon Some materials (enzymes, ion channels) made in cell body must be transported to the axon and terminal Anterograde transport—movement away from cell body, down the axon; driven by motor protein kinesin Other materials need to be transported from axon terminals back to cell body for disposal Retrograde transport—movement up the axon toward the cell body; driven by motor protein dynein © McGraw Hill, LLC 24  Axonal Transport 2 Axonal transport can be fast or slow Fast axonal transport—200 to 400 mm/day and may be anterograde or retrograde Fast anterograde transport of organelles, enzymes, synaptic vesicles, small molecules Fast retrograde transport for recycled materials, some pathogens Slow axonal transport—0.2 to 0.5 mm/day; “stop-and-go” movement results in slower overall speed; always anterograde Transport of enzymes, cytoskeletal components, new axoplasm Damaged nerves regenerate at a speed governed by slow axonal transport © McGraw Hill, LLC 25  12.3 Supportive Cells 1 Expected Learning Outcomes: Name the six types of cells that aid neurons, and state their respective functions. Describe the myelin sheath that is found around certain axons, and explain its importance. Describe the relationship of unmyelinated axons to their supportive cells. Explain how damaged axons regenerate. © McGraw Hill, LLC 26  Supportive Cells 2 Approximately 86 billion neurons in the adult brain, and a roughly equal number of neuroglia, or glial cells—non- neuronal supportive cells Overview of functions: Bind neurons together Form supportive tissue framework In fetus, guide migrating neurons to their destination Cover mature neurons (except at synapses) Prevents neurons from touching each other Gives precision to conduction pathways © McGraw Hill, LLC 27  12.3a Types of Glia 1 Approximately 86 billion neurons in the adult brain, and a roughly equal number of neuroglia, or glial cells—non-neuronal supportive cells Four types of glia occur in the CNS: Oligodendrocytes—form myelin sheaths in CNS Ependymal cells—line internal cavities of brain; secrete and circulate cerebrospinal fluid (CSF) Microglia—macrophages; engulf debris, provide defense against pathogens Astrocytes—most abundant type; wide variety of functions Provide framework for nervous tissue; extensions (perivascular feet) contact capillaries and stimulate formation of blood-brain barrier; adjust blood flow; supply neurons with lactate for energy; secrete nerve growth factors; influence synaptic signaling; regulate composition of tissue fluid; form scar tissue when neurons are damaged, a process called astrocytosis or sclerosis © McGraw Hill, LLC 28  Neuroglia of the Central Nervous System Access the text alternative for slide images. Figure 12.6 © McGraw Hill, LLC 29  Types of Glia 2 Remaining types are peripheral glia cells, found only in the peripheral nervous system Two types: Schwann cells, or neurolemmocytes—envelop axons of PNS, form myelin sheath, and assist in regeneration of damaged fibers Satellite cells—surround nerve cell bodies in ganglia of PNS; provide insulation around cell body and regulate chemical environment © McGraw Hill, LLC 30  Glial Cells and Brain Tumors Tumors are masses of rapidly dividing cells Mature neurons have little or no capacity for mitosis and seldom form tumors Brain tumors arise from: Meninges (protective membranes of CNS) Metastasis from nonneuronal tumors in other organs Glial cells that are mitotically active throughout life Gliomas—tumors of glial cells; grow rapidly and are highly malignant Blood–brain barrier decreases effectiveness of chemotherapy Treatment consists of radiation or surgery © McGraw Hill, LLC 31  Brain Tumor CNRI/Science Source Figure 12.7 © McGraw Hill, LLC 32  12.3b Myelin 1 Myelin sheath—spiral layers of insulation around an axon Formed by Schwann cells in PNS, oligodendrocytes in CNS Sheath consists of the plasma membrane of these cells, 20% protein and 80% lipid Production of sheath is called myelination Begins during fetal development, proceeds rapidly during infancy, complete by late adolescence © McGraw Hill, LLC 33  Myelin 2 Myelination in the PNS: A Schwann cell spirals repeatedly around a small section of a single axon Lays down as many as 100 layers of its membrane with no cytoplasm between the layers These layers are the myelin sheath Neurilemma—thick, outermost coil Contains Schwann cell nucleus and most of its cytoplasm External to neurilemma: Basal lamina Endoneurium—a thin layer of fibrous connective tissue © McGraw Hill, LLC 34  Myelination 1 Access the text alternative for slide images. Figure 12.8a © McGraw Hill, LLC 35  Myelination 2 c: Dr. Dennis Emery/Iowa State Universit/McGraw Hill Access the text alternative for slide images. Figure 12.8c © McGraw Hill, LLC 36  Myelin 3 Myelination in the CNS: Each oligodendrocyte extends several processes that wrap around small portions of many axons in its immediate vicinity During myelination, nucleus cannot migrate around the axon like a Schwann cell does Must push newer layers of myelin under the older ones, so myelination spirals inward toward axon No neurilemma © McGraw Hill, LLC 37  Myelination 3 Access the text alternative for slide images. Figure 12.8b © McGraw Hill, LLC 38  Myelin 4 In both the PNS and CNS, the myelin sheath is segmented Many Schwann cells (PNS) or oligodendrocytes (CNS) are needed to myelinate one axon Each segment of axon wrapped by different glial cell Myelin sheath gap (node of Ranvier)—gap between segments Internodal segments—myelin-covered segments Initial segment—bare section of axon between the axon hillock and the first glial cell Trigger zone—axon hillock and initial segment Plays important role in initiating nerve signal © McGraw Hill, LLC 39  Diseases of the Myelin Sheath 1 Multiple sclerosis (MS): Oligodendrocytes and myelin sheaths in CNS deteriorate Myelin replaced by hardened scar tissue Nerve conduction disrupted (double vision, tremors, numbness, speech defects) Onset between 20 and 40 and fatal from 25 to 30 years after diagnosis Cause may be autoimmune triggered by virus © McGraw Hill, LLC 40  Diseases of the Myelin Sheath 2 Tay–Sachs disease: Hereditary disorder seen mainly in infants of Eastern European Jewish ancestry Usually fatal before age 4 Abnormal accumulation of glycolipid called GM2 in the myelin sheath Normally decomposed by lysosomal enzyme Enzyme missing in individuals homozygous for Tay–Sachs allele Accumulation of ganglioside (GM2 ) disrupts conduction of nerve signals Causes blindness, loss of coordination, dementia © McGraw Hill, LLC 41  12.3c Unmyelinated Axons 1 Many axons in CNS and PNS are unmyelinated In PNS, Schwann cells hold small unmyelinated axons in surface grooves Membrane folds once around each axon; does not spiral repeatedly around it This wrap serves as the neurolemma Basal lamina surrounds Schwann cell along with its axons © McGraw Hill, LLC 42  Unmyelinated Axons 2 Access the text alternative for slide images. Figure 12.9 © McGraw Hill, LLC 43  12.3d Conduction Speed of Axons Speed at which a nerve signal travels down an axon depends on two factors: Diameter: larger axons have more surface area and conduct signals more rapidly Presence or absence of myelin: myelin speeds signal conduction Examples: Small, unmyelinated fibers: about 0.5 to 2.0 m/s Small, lightly myelinated fibers: 3 to 15.0 m/s Large, myelinated fibers: up to 120 m/s © McGraw Hill, LLC 44  12.3e Nerve Regeneration 1 Regeneration of damaged PNS nerve fiber (axon) can occur if nerve cell bodies are intact and at least some neurilemma remains Steps of regeneration: Axon distal to the injury degenerates, macrophages clean up tissue debris Cell body swells, ER breaks up, and nucleus moves off center Changes due to loss of nerve growth factors from target cell Axon stump sprouts multiple growth processes Schwann cell neurolemma, endoneurium, and basal lamina form a regeneration tube Guides regrowth to original destination © McGraw Hill, LLC 45  Nerve Regeneration 2 Steps of regeneration (continued): Once contact is reestablished with original target, the neurosoma shrinks and returns to its original appearance Nucleus returns to normal shape Atrophied muscle fibers regrow Regeneration is not fast, perfect, or always possible Slow regrowth; process may take 2 years Some axons connect with wrong muscle fibers; some die Damaged CNS axons usually unable to regenerate © McGraw Hill, LLC 46  Regeneration of a Damaged Axon 1 Access the text alternative for slide images. Figure 12.10(1,2) © McGraw Hill, LLC 47  Regeneration of a Damaged Axon 2 Access the text alternative for slide images. Figure 12.10(3,4) © McGraw Hill, LLC 48  Regeneration of a Damaged Axon 3 Access the text alternative for slide images. Figure 12.10(5,6) © McGraw Hill, LLC 49  12.4 Electrophysiology of Neurons Expected Learning Outcomes: Explain why a cell has an electrical charge difference (voltage) across its membrane. Explain how stimulation of a neuron causes a local electrical response in its membrane. Explain how local responses generate a nerve signal. Explain how the nerve signal is conducted down an axon. © McGraw Hill, LLC 50  12.4a Electrical Potentials and Currents 1 Neural communication is based on electrical potentials and currents Electrical potential—difference in concentration of charged particles between one point and another Type of potential energy; measured in volts Under some conditions, can produce a current Current—flow of charged particle from one point to another Example: flashlight battery Has a potential (charge) of 1.5 volts Can produce a current of electrons that lights the bulb With a potential (voltage), the battery is polarized Living cells are also polarized © McGraw Hill, LLC 51  Electrical Potentials and Currents 2 Resting membrane potential (RMP)—charge difference across plasma membrane Typically −70 millivolts (mV) in an unstimulated, “resting” neuron Negative value indicates more negatively charged particles on inside of membrane compared to outside Electrical currents in the body created by flow of ions (Na + , K + , etc.) through gated channels in the membrane © McGraw Hill, LLC 52  12.4b The Resting Membrane Potential 1 Ionic basis of the resting membrane potential (RMP): Ions are unequally distributed between extracellular fluid (ECF) and intracellular fluid (ICF) RMP results from the combined effect of: The diffusion of ions down their concentration gradients through the membrane Selective permeability of the membrane, allowing some ions to pass more easily than others Electrical attraction of cations and anions to each other © McGraw Hill, LLC 53  The Resting Membrane Potential 2 Ionic basis of the resting membrane potential (continued): Potassium (K + ) has greatest influence on RMP K + is more concentrated in ICF compared to ECF Cell membrane more permeable to K + (through leak channels) than to other ions + As K leaks out, inside of membrane becomes more negative Resulting electrical attraction brings K + back in Equilibrium is reached: no net movement of K + occurs when tendency for K + to exit (down its concentration gradient) equals tendency for K + to enter (by electrical attraction) © McGraw Hill, LLC 54  The Resting Membrane Potential 3 Ionic basis of the resting membrane potential (continued): Sodium (Na + ) also influences the RMP Na + is more concentrated in ECF compared to ICF, but membrane is much less permeable to Na + than to K + Na diffuses into the cell, down its concentration gradient and + attracted electrically, but it’s a relatively small amount Cancels some of the negative charge, reducing the voltage across the membrane © McGraw Hill, LLC 55  The Resting Membrane Potential 4 Ionic basis of the resting membrane potential (continued): Sodium-potassium (Na  /K  ) pump compensates for the + + continual leakage of Na and K Moves Na + out of the cell and brings K + into the cell— maintains their concentration gradients Contributes about -3 mV to the RMP Works continuously and requires ATP 70% of the energy requirement of the nervous system © McGraw Hill, LLC 56  Ionic Basis of the Resting Membrane Potential Access the text alternative for slide images. Figure 12.12 © McGraw Hill, LLC 57  12.4c Local Potentials 1 Sensory neurons can be stimulated by chemicals, light, heat, or mechanical forces Stimulation triggers local, temporary change in membrane potential Example: chemical stimulant binds to a receptor on the neuron Opens Na + channels, allows Na + to enter Entry of positively charged Na + makes membrane potential less negative Polarity is reduced, voltage is less negative—called depolarization Depolarization spreads from the point of stimulation Temporary, short-range change in voltage is a local potential © McGraw Hill, LLC 58  Local Potentials 2 Characteristics of local potentials: Graded—vary in magnitude with stimulus strength Stronger stimuli open more Na + channels, and they stay open longer Decremental—get weaker the farther they spread from the point of stimulation Reversible—if stimulation ceases, membrane voltage quickly returns to normal resting potential Can be either excitatory or inhibitory Depolarization is excitatory—makes a neuron more likely to fire an action potential) Hyperpolarization (membrane more negative) is inhibitory—makes a neuron less likely to produce an action potential © McGraw Hill, LLC 59  Excitation of a Neuron by a Chemical Stimulus Access the text alternative for slide images. Figure 12.13 © McGraw Hill, LLC 60  12.4d Action Potentials 1 Action potential—rapid up-and-down change in voltage produced by the coordinated opening and closing of voltage- gated ion channels Only occurs where there is a high enough density of voltage-gated ion channels (trigger zone of axon) If excitatory local potential reaches trigger zone and is still strong enough, it opens enough voltage-gated Na + channels to generate an action potential © McGraw Hill, LLC 61  Action Potentials 2 Steps of an action potential: Local potential spreads to axon hillock Voltage at axon hillock must reach threshold—the minimum voltage to open voltage-gated channels (around −55 mV) Voltage-gated Na + channels open quickly Voltage-gated K + channels open more slowly Na + enters and depolarizes membrane further, quickly surpassing 0 mV Na + channels become inactivated, begin closing Voltage peaks at +35 mV by the time Na + inflow ceases Membrane polarity has reversed—now more positive on the inside and negative on the outside © McGraw Hill, LLC 62  Action Potentials 3 Steps of an action potential (continued): The voltage-gated K + are fully open, K + flows out of cell and membrane becomes more negative again—repolarization K + continues to exit and produces a negative overshoot hyperpolarization) 1 to 2 mV more negative than the original RMP Membrane voltage returns to RMP as Na + leaks into the cell © McGraw Hill, LLC 63  An Action Potential Access the text alternative for slide images. Figure 12.14 © McGraw Hill, LLC 64  Actions of the Sodium and Potassium Channels During an Action Potential 1 Access the text alternative for slide images. Figure 12.15(1,2) © McGraw Hill, LLC 65  Actions of the Sodium and Potassium Channels During an Action Potential 2 Access the text alternative for slide images. Figure 12.15(3,4) © McGraw Hill, LLC 66  Action Potentials 4 The concentrations of Na  and K + on either side of the membrane do not change significantly during an action potential Movement of only a few ions can have a large effect on the membrane potential Only about one in a million ions crosses the membrane during an action potential Only the thin layer of ions close to the membrane is affected Even after thousands of action potentials, the cytosol still has a higher concentration of K + and a lower concentration of Na + than the ECF © McGraw Hill, LLC 67  Action Potentials 5 Characteristics of action potentials: All-or-none law—if threshold reached, neuron fires up to maximum voltage; if threshold not reached, it does not fire Non decremental—do not get weaker with distance Irreversible—once started, an action potential travels all the way down the axon cannot be stopped © McGraw Hill, LLC 68  12.4e The Refractory Period Refractory period—period of resistance to stimulation; has two phases: Absolute refractory period—no stimulus of any strength will trigger another AP Caused by inactivation of voltage-gated Na+ channels Relative refractory period—an unusually strong stimulus is needed to trigger a new AP During hyperpolarization, a larger depolarization (local potential) is required to reach threshold © McGraw Hill, LLC 69  The Absolute and Relative Refractory Periods in Relation to the Action Potential Access the text alternative for slide images. Figure 12.16 © McGraw Hill, LLC 70  12.4f Signal Conduction in Nerve Fibers 1 Unmyelinated axons and continuous conduction: Unmyelinated axons have voltage-gated channels along their entire length Action potential at trigger zone causes Na + to enter axon and diffuse into adjacent regions Depolarization opens voltage-gated channels Opening of voltage-gated ion channels results in a new action potential which then allows Na + diffusion to excite membrane immediately distal to that Chain-reaction continues down axon Like a wave of falling dominoes Called continuous conduction © McGraw Hill, LLC 71  Continuous Conduction of a Nerve Signal in an Unmyelinated Axon Access the text alternative for slide images. Figure 12.17 © McGraw Hill, LLC 72  Signal Conduction in Nerve Fibers 2 Myelinated axons and saltatory conduction: Action potentials can only be generated at the nodes, where voltage-gated ion channels are concentrated Electrical signal must spread passively between nodes Signal passes very quickly, but strength decreases (similar to a local potential) When signal reaches the next node it is still strong enough to depolarize the membrane to threshold Voltage gated Na+ channels open and a new, full-strength action potential occurs Action potential seems to “jump” from node to node Moves faster through “insulated” segments covered with myelin Slows down when it reaches the bare axon of the nodes © McGraw Hill, LLC 73  Saltatory Conduction of a Nerve Signal in a Myelinated Axon 1 Access the text alternative for slide images. Figure 12.18a © McGraw Hill, LLC 74  Saltatory Conduction of a Nerve Signal in a Myelinated Axon 2 Access the text alternative for slide images. Figure 12.18b © McGraw Hill, LLC 75  12.5 Synapses 1 Expected Learning Outcomes: Explain how messages are transmitted from one neuron to another. Give examples of neurotransmitters and neuromodulators and describe their actions. Explain how stimulation of a postsynaptic cell is stopped. © McGraw Hill, LLC 76  Synapses 2 Synapse—point where an axon terminal meets the next cell (another neuron, gland cell, muscle cell) For neuron-to-neuron synapses: Action potential arrives at end of axon of presynaptic neuron Presynaptic neuron releases neurotransmitter The postsynaptic neuron responds to it © McGraw Hill, LLC 77  Synaptic Relationships Between Neurons Access the text alternative for slide images. Figure 12.19 © McGraw Hill, LLC 78  12.5a The Discovery of Neurotransmitters 1 The synaptic cleft (gap between neurons) was discovered by Ramón y Cajal through histological observations Otto Loewi, in 1921, demonstrated that neurons can communicate by releasing chemicals Flooded exposed hearts of two frogs with saline Stimulated vagus nerve of first frog and its heart slowed Removed saline from first frog and found it slowed heart of second frog Named it Vagusstoff (“vagus substance”) Later renamed acetylcholine, the first known neurotransmitter © McGraw Hill, LLC 79  The Discovery of Neurotransmitters 2 Neurotransmitters are released at chemical synapses There are also electrical synapses Occur between some neurons, neuroglia, and cardiac and single-unit smooth muscle Gap junctions join adjacent cells; electrical signals spread directly from cell to cell Advantage—much faster; no delay for release, diffusion, and binding of neurotransmitter Disadvantage—cannot integrate information © McGraw Hill, LLC 80  12.5b Structure of a Chemical Synapse 1 Synaptic cleft—gap between presynaptic neuron and postsynaptic neuron; typically only 20 um wide Each neuron has cell-adhesion molecules (CAMs) reaching into the cleft CAMs link the two neurons together Axon terminal of presynaptic neuron contains synaptic vesicles containing neurotransmitter Many vesicles are docked on release sites on plasma membrane ready to release neurotransmitter Postsynaptic neuron membrane contains a postsynaptic density of neurotransmitter receptors and ion channels Ligand-gated ion gates open when neurotransmitters bind to them © McGraw Hill, LLC 81  Synapses 3 Omikron/Science Source/Getty Images Access the text alternative for slide images. Figure 12.20a © McGraw Hill, LLC 82  Synapses 4 DENNIS KUNKEL MICROSCOPY/Science Source Access the text alternative for slide images. Figure 12.20 © McGraw Hill, LLC 83  Structure of a Chemical Synapse 2 Access the text alternative for slide images. Figure 12.21 © McGraw Hill, LLC 84  12.5c Neurotransmitters and Related Messengers 1 More than 100 neurotransmitters have been identified, most falling into these major chemical categories: Acetylcholine—formed from acetic acid and choline Amino acids—include glycine, glutamate, aspartate, and γ-aminobutyric acid (GABA) Monoamines (biogenic amines)—synthesized from amino acids by removal of the –COOH group but retain the amino group Examples: the catecholamines epinephrine, norepinephrine, and dopamine; also serotonin, histamine Purines—adenosine, ATP © McGraw Hill, LLC 85  Neurotransmitters and Related Messengers 2 Major chemical categories of neurotransmitters (continued): Gases—nitric oxide (N O) and carbon monoxide (C O); synthesized as needed rather than stored in vesicles Neuropeptides—chains of 2-40 amino acids; cholecystokinin (C C K) and endorphins Stored in large secretory granules (dense-core vesicles) Some also function as hormones or neuromodulators © McGraw Hill, LLC 86  Classification of Some Neurotransmitters Access the text alternative for slide images. Figure 12.22 © McGraw Hill, LLC 87  12.5d Synaptic Transmission 1 Synapses are variable in their modes of action Some neurotransmitters are excitatory, others inhibitory, and sometimes a transmitter’s effect differs depending on type of receptor on postsynaptic cell Some receptors are ligand-gated ion channels; others act through intracellular second messengers Examples of three kinds of synapses: Excitatory cholinergic synapse Inhibitory GABA-ergic synapse Excitatory adrenergic synapse © McGraw Hill, LLC 88  Synaptic Transmission 2 An excitatory cholinergic synapse Cholinergic synapse—acetylcholine (ACh) is the neurotransmitter Steps in synaptic transmission: Action potential depolarizes the axon terminal, opens voltage-gated Ca 2+ channels Ca 2+ enters, triggers exocytosis of ACh ACh diffuses across cleft, binds to postsynaptic receptors ACh receptors are ligand-gated ion channels that open and allow Na + and K + across the membrane Entry of Na + causes depolarizing postsynaptic potential If strong enough, depolarization spreads to the trigger zone, raises the membrane potential up to threshold to trigger an action potential © McGraw Hill, LLC 89  Transmission at a Cholinergic Synapse 1 Access the text alternative for slide images. Figure 12.23 © McGraw Hill, LLC 90  Synaptic Transmission 3 An inhibitory GABA-ergic synapse GABA-ergic synapse—γ-aminobutyric acid (GABA) is the neurotransmitter Steps in synaptic transmission: Action potential triggers release of GABA into synaptic cleft GABA receptors are chloride channels Cl- entry hyperpolarizes the postsynaptic membrane Postsynaptic neuron inhibited—less likely to fire action potential © McGraw Hill, LLC 91  Synaptic Transmission 4 An excitatory adrenergic synapse Adrenergic synapse—norepinephrine (NE) is the neurotransmitter NE is also called noradrenaline Monoamines and neuropeptides bind to G-protein coupled receptors on postsynaptic membrane Activate second-messenger systems such as cyclic AMP (cAMP) Slower to respond than cholinergic and GABA-ergic synapses Has advantage of enzyme amplification Single molecule of NE produces vast numbers of product molecules in cell © McGraw Hill, LLC 92  Transmission at an Adrenergic Synapse Access the text alternative for slide images. Figure 12.24 © McGraw Hill, LLC 93  12.5e Cessation of the Signal 1 It is important not only to stimulate a postsynaptic cell but also to turn off the stimulus Neurotransmitter stays bound to receptor for about 1 ms If the presynaptic cell continues to release neurotransmitter, one molecule is quickly replaced by another and the postsynaptic cell continues to be stimulated To end the signal: Presynaptic cell stops releasing neurotransmitter Neurotransmitter already in synapse is cleared in various ways © McGraw Hill, LLC 94  Cessation of the Signal 2 Clearance of neurotransmitter: Neurotransmitter degradation—enzyme in synaptic cleft breaks down neurotransmitter Example: acetylcholinesterase (AChE) breaks ACh down into choline and acetate Reuptake—neurotransmitter or its breakdown products reabsorbed into axon terminal Example: choline from ACh recycled to make new ACh Amino acids and monoamines also reabsorbed, degraded in axon terminal by enzyme monoamine oxidase (MAO)—target of some antidepressant drugs Diffusion—neurotransmitter or its breakdown products simply away from synapse into nearby ECF © McGraw Hill, LLC 95  Transmission at a Cholinergic Synapse 2 Access the text alternative for slide images. Figure 12.23 © McGraw Hill, LLC 96  12.5f Neuromodulators Neuromodulators—chemicals secreted by neurons that have long term effects on groups of neurons May alter the rate of neurotransmitter synthesis, release, reuptake, or breakdown May adjust sensitivity of postsynaptic membrane Nitric oxide (N O) is a simple neuromodulator Gas that enters postsynaptic cells and activates second messenger pathways (for example, relaxing smooth muscle) Neuropeptides are chains of amino acids that can act as neuromodulators Enkephalins and endorphins are neuropeptides that inhibit pain signals in the C N S © McGraw Hill, LLC 97  12.6 Neural Integration 1 Expected Learning Outcomes: Explain how a neuron “decides” whether or not to generate action potentials. Explain how the nervous system translates complex information into a simple code. Explain how neurons work together in groups to process information and produce effective output. Describe how memory works at the cellular and molecular levels. © McGraw Hill, LLC 98  Neural Integration 2 Neural integration—the ability to process, store, and recall information and use it to make decisions Chemical synapses allow for decision-making Brain cells are incredibly well connected, allowing for complex integration Pyramidal cells of cerebral cortex have about 40,000 contacts with other neurons Trade off: chemical transmission involves a synaptic delay that makes information travel slower than it would if there was no synapse © McGraw Hill, LLC 99  12.6a Postsynaptic Potentials 1 Two types of postsynaptic potentials produced by neurotransmitters: Excitatory postsynaptic potential (EPSP)—voltage change from the RMP toward threshold An EPSP usually results from Na + flowing into the cell Inhibitory postsynaptic potential (IPSP)—voltage becomes more negative than it is at rest An IPSP can result from Cl- entry or K + exit from cell © McGraw Hill, LLC 100  Postsynaptic Potentials 2 Access the text alternative for slide images. Figure 12.25 © McGraw Hill, LLC 101  Postsynaptic Potentials 3 Different neurotransmitters cause different types of postsynaptic potentials. Glutamate and aspartate produce EPSPs in brain cells Glycine and GABA produce IPSPs A neurotransmitter might excite some cells and inhibit others, depending on the type of receptors in the postsynaptic membrane Acetylcholine (ACh) and norepinephrine work this way ACh excites skeletal muscle but inhibits cardiac muscle due to the expression of different types of ACh receptors on the different types of muscle cells © McGraw Hill, LLC 102  12.6b Summation, Facilitation, and Inhibition 1 Summation—the process of adding up postsynaptic potentials and responding to their net effect Occurs in the trigger zone Some incoming nerve fibers may produce EPSPs while others produce IPSPs A neuron’s response depends on whether the net input is excitatory or inhibitory The balance between EPSPs and IPSPs enables the nervous system to make decisions © McGraw Hill, LLC 103  Summation, Facilitation, and Inhibition 2 Two ways EPSPs can be added to reach threshold: Temporal summation—a single synapse generates EPSPs so quickly that each is generated before the previous one fades Allows EPSPs to add up over time to a threshold voltage that triggers an action potential Spatial summation—EPSPs from several different synapses add up to threshold at an axon hillock Simultaneous input from multiple presynaptic neurons required for the postsynaptic neuron to fire An example of facilitation—a process in which one neuron enhances the effect of another © McGraw Hill, LLC 104  Temporal and Spatial Summation Access the text alternative for slide images. Figure 12.26 © McGraw Hill, LLC 105  Summation of EPSPs Access the text alternative for slide images. Figure 12.27 © McGraw Hill, LLC 106  Summation, Facilitation, and Inhibition 3 Neurons can work in groups to modify each other’s actions Presynaptic facilitation—occurs when one presynaptic neuron enhances another one Increases necessary synaptic transmission Example: facilitating neuron (cell “F” in figure) releases serotonin which makes voltage-gated calcium channels in axon terminal (“S” in figure) stay open longer © McGraw Hill, LLC 107  Presynaptic Facilitation Access the text alternative for slide images. Figure 12.28 © McGraw Hill, LLC 108  Summation, Facilitation, and Inhibition 4 Neurons can work in groups (continued): Presynaptic inhibition—occurs when one presynaptic neuron suppresses another one Reduces or halts unwanted synaptic transmission Example: Inhibiting neuron (cell “I” in figure) releases GABA which prevents voltage-gated calcium channels in axon terminal (“S” in figure) from opening and so little or no neurotransmitter is released © McGraw Hill, LLC 109  Presynaptic Inhibition Access the text alternative for slide images. Figure 12.29 © McGraw Hill, LLC 110  12.6c Neural Coding Neural coding—converting stimulus information into meaningful pattern of action potentials Labeled line code—mechanism for transmitting qualitative information (type of stimulus) Depends on which neurons fire; for example, optic nerve input labeled as “light” Quantitative information (intensity of a stimulus) encoded in two ways: Weak stimuli only activate sensitive “low threshold” neurons; strong stimuli also activate less sensitive “high threshold” neurons through recruitment Weak stimuli cause neurons to fire action potentials at a slower rate, strong stimuli cause higher firing frequency © McGraw Hill, LLC 111  An Example of Neural Coding Access the text alternative for slide images. Figure 12.30 © McGraw Hill, LLC 112  12.6d Neural Pools and Circuits 1 Neural pools—functional groupings of neurons; each pool consists of thousands of interneurons concerned with a particular body function Examples: Control rhythm of breathing Moving limbs rhythmically when walking © McGraw Hill, LLC 113  Neural Pools and Circuits 2 Discharge and facilitated zones Information arrives at neural pool through input neurons Within input neuron’s discharge zone, it can act alone to make postsynaptic cells fire In its broader facilitated zone, input neuron makes fewer, less powerful synapses Can only stimulate targets with the assistance of other input neurons Access the text alternative for slide images. Figure 12.31 © McGraw Hill, LLC 114  Neural Pools and Circuits 3 Types of neural circuits: Diverging circuit—one nerve fiber branches and synapses with several postsynaptic cells Converging circuit—input from many different nerve fibers can be funneled to one neuron or neural pool Access the text alternative for slide images. Figure 12.32(top) © McGraw Hill, LLC 115  Neural Pools and Circuits 4 Types of neural circuits (continued): Reverberating circuit—neurons stimulate each other in linear sequence but one or more of the later cells restimulates the first cell to start the process all over Parallel after-discharge circuit—input neuron diverges to stimulate several chains of neurons Neuron chains with different number of synapses converge on one or a few output neurons, but with varying delays After-discharge—continued firing after the stimulus stops Access the text alternative for slide images. Figure 12.32(bottom) © McGraw Hill, LLC 116  Neural Pools and Circuits 5 Serial and parallel processing of information Serial processing—neurons and neural pools relay information along pathway in relatively simple linear fashion Can process only one flow of information at a time Read a book or watch a television movie—you cannot do both simultaneously May jump back and forth between one and the other, or only half understanding each © McGraw Hill, LLC 117  Neural Pools and Circuits 6 Serial and parallel processing of information (continued): Parallel processing—information is transmitted along diverging circuits through different pathways that act on it simultaneously, for different purposes For example, when you’re driving your car, your visual system (eye and brain) must simultaneously process information about color, shape, depth of field, and motion in the scene before your eyes At the same time, you must process traffic sounds and signals from your body’s own motion sensors © McGraw Hill, LLC 118  12.6e Memory and Synaptic Plasticity 1 Memory trace (engram)—pathway of synapses through the brain; physical basis of memory Along this pathway, new synapses are created or existing synapses modified to make transmission easier Synaptic plasticity—ability of synapses to change Synaptic potentiation—process of making transmission easier Three kinds of memory: Immediate memory, short-term memory, and long-term memory Correlated with different modes of synaptic potentiation that last from a few seconds to a lifetime © McGraw Hill, LLC 119  Memory and Synaptic Plasticity 2 Immediate memory Immediate memory—ability to hold something in your thoughts for a few seconds Essential for reading ability Feel for the flow of events (sense of the present) Our memory of what just happened “echoes” in our minds for a few seconds May depend on reverberating circuits © McGraw Hill, LLC 120  Memory and Synaptic Plasticity 3 Short-term memory Short-term memory (STM)—lasts from seconds to a few hours Includes working memory for taking action Example: calling a phone number you just looked up Synaptic facilitation—making it easier to transmit signals across a synapse; important in memory formation Tetanic stimulation—rapid arrival of repetitive signals at a synapse Causes Ca 2+ accumulation in terminal, more neurotransmitter released Post tetanic potentiation—calcium level in axon terminal stays elevated, results in exceptionally large burst of neurotransmitter May be involved in jogging a memory from a few hours ago Little stimulation needed to recover memory © McGraw Hill, LLC 121  Memory and Synaptic Plasticity 4 Long-term memory Long-term memory (LTM)—lasts up to a lifetime and can hold more information than short term memory Two types of LTM: Explicit (declarative) memory—memories you can put into words (numbers, names, dates, etc); must think to remember these Implicit memory—reflexive or unconscious memory; includes emotional memories (bee stings hurt) and procedural (motor skill) memories Some LTM involves formation or remodeling of synapses New branching of axons or dendrites Some LTM may involve molecular changes called long- term potentiation (LTP) © McGraw Hill, LLC 122  Memory and Synaptic Plasticity 5 How we forget Long-term depression—low-frequency stimulation of a synapse results in low levels of intracellular Ca 2+ Low calcium concentration activates protein phosphatases, which dephosphorylate synaptic proteins such as actin microfilaments that support dendritic spines These proteins are then degraded by proteasomes, which tear down dendritic spines and remove little-used synapses from the neural circuits © McGraw Hill, LLC 123  Alzheimer Disease 1 Alzheimer disease (AD) causes 100,000 deaths/year; affects 11% of population over 65 and 47% by age 85 Symptoms: Memory loss, moody, combative, and lose ability to talk, walk, and eat Acetylcholine (ACh) and nerve growth factor (NGF) deficiencies Diagnosis confirmed at autopsy Atrophy of gyri (folds) in cerebral cortex Neurofibrillary tangles and senile plaques Formation of β-amyloid protein from breakdown product of plasma membranes Treatment possibilities Find ways to clear β-amyloid or halt its production, but research halted due to serious side effects © McGraw Hill, LLC 124  Alzheimer Disease 2 a: © Science Source; b: © Jose Luis Calvo/Shutterstock Access the text alternative for slide images. Figure 12.33 © McGraw Hill, LLC 125  Parkinson Disease 1 Parkinson disease (PD)—progressive loss of motor function due to degeneration of dopamine-releasing neurons Dopamine normally prevents excessive activity in motor centers (basal nuclei) Symptoms: Involuntary muscle contractions Pill-rolling motion, facial rigidity, slurred speech Illegible handwriting, slow gait Treatment—drugs and physical therapy Dopamine precursor (L-dopa) crosses brain barrier; bad side effects on heart and liver MAO inhibitor slows neural degeneration Surgical technique to relieve tremors © McGraw Hill, LLC 126  Parkinson Disease 2 a-b: ISM/Pr J.J. Hauw/Medical Images Access the text alternative for slide images. Figure 12.34 © McGraw Hill, LLC 127  End of Main Content Because learning changes everything. ® www.mheducation.com © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC.