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Chapter 9 Nervous Tissue Copyright 2010, John Wiley & Sons, Inc. Structures of the Nervous System Brain: neurons enclosed within skull Spinal cord: connects to brain and enclosed within spinal cavity Nerves: bundles of many axons of neurons Cranial nerves (12 pairs) emerge from brain Spinal nerves (31 pairs) emerge from spinal cord Ganglia: groups of neuron cell bodies located outside of brain and spinal cord Enteric plexuses: networks in digestive tract Sensory receptors: monitor changes in internal or external environments Copyright 2010, John Wiley & Sons, Inc. Structures of the Nervous System Copyright 2010, John Wiley & Sons, Inc. Functions of the Nervous System Sensory receptors and sensory nerves Integration: information processing Carry information into brain and spinal cord Perception = awareness of sensory input Analyzing and storing information to help lead to appropriate responses Motor activity: efferent nerves Signals to muscles and glands (effectors) Copyright 2010, John Wiley & Sons, Inc. Organization of the Nervous System Central Nervous System (CNS) Brain and spinal cord Peripheral Nervous System (PNS) All nervous system structures outside of the CNS Copyright 2010, John Wiley & Sons, Inc. Histology of the Nervous System Neurons Can respond to stimuli and convert stimuli to electrical signals (nerve impulses) that travel along neurons Neuroglia cells: support, nourish and protect neurons Neuroglia critical for homeostasis of interstitial fluid around neurons Copyright 2010, John Wiley & Sons, Inc. Neuronal Structure Cell body: nucleus, cytoplasm with typical organelles Dendrites: highly branched structures that carry impulses to the cell body Axon: conducts away from cell body toward another neuron, muscle or gland Emerges at cone-shaped axon hillock Axon terminals: contain synaptic vesicles that can release neurotransmitters Copyright 2010, John Wiley & Sons, Inc. Neuronal Structure Copyright 2010, John Wiley & Sons, Inc. Structural Classes of Neurons Multipolar Bipolar Have several or many dendrites and one axon Most common type in brain and spinal cord Have one dendrite and one axon Example: in retina of eye and inner ear Unipolar Have fused dendrite and axon Sensory neurons of spinal nerves Copyright 2010, John Wiley & Sons, Inc. Functional Classes of Neurons Sensory (afferent) Motor (efferent) Convey impulses into CAN (brain or spinal cord) Convey impulses from brain or spinal cord out through the PNS to effectors (muscles or glands) Interneurons (association neurons) Most are within the CNS Transmit impulses between neurons, such as between sensory and motor neurons Copyright 2010, John Wiley & Sons, Inc. Neuroglia Cells smaller but much more numerous than neurons Can multiply and divide and fill in brain areas Gliomas: brain tumors derived from neuroglia Functions Do not conduct nerve impulses Do support, nourish and protect neurons Copyright 2010, John Wiley & Sons, Inc. Neuroglia Astrocytes: help form blood brain barrier Oligodendrocytes: produce myelin in CNS Microglia: protect CNS cells from disease Ependymal cells: form CSF in ventricles Schwann: produce myelin around PNS neurons; help to regenerate PNS axons Satellite cells: support neurons in PNS ganglia Copyright 2010, John Wiley & Sons, Inc. Myelination Axons covered with a myelin sheath Nodes of Ranvier: gaps in the myelin Many layers of lipid and protein: insulates neurons Increases speed of nerve conduction Appears white (in white matter) Nodes are important for rapid signal conduction Some diseases destroy myelin: Multiple sclerosis Tay-Sachs Copyright 2010, John Wiley & Sons, Inc. Collections of Nervous Tissue Clusters of neuron cell bodies Ganglion: cluster of cell bodies in PNS Nucleus: cluster of cell bodies in CNS Bundles of axons Nerve: bundle of axons in PNS Tract: bundle to axons in CNS Copyright 2010, John Wiley & Sons, Inc. Gray and White Matter White matter: primarily myelinated axons Gray matter: cell bodies, dendrites, unmyelinated axons, axon terminals, neuroglia Locations of gray and white matter Spinal cord: white matter (tracts) surround centrally located gray matter “H” of “butterfly” Brain: gray matter in thin cortex surrounds white matter (tracts) Copyright 2010, John Wiley & Sons, Inc. Grey & White matter Neuron Regeneration Regeneration of PNS neurons Axons and dendrite in the PNS can be repaired if cell body is intact and Schwann cells functional. These form a regeneration tube and grow axons or dendrites if scar tissue does not fill the tube Regeneration of CNS neurons Very limited even if cell body is intact Inhibited by neuroglia and by lack of fetal growthstimulators “Unique cells in neuronal tissues, called olfactory ensheathing glia (OEG) cells, have been reported to be the only nerve cells of the CNS capable of constant regeneration; They have successfully been used to partially recover the locomoter activity in dogs paralyzed due to traumatic spinal cord injury!" Copyright 2010, John Wiley & Sons, Inc. Organization of the Nervous System Central nervous system (CNS) structures: Brain Spinal cord Peripheral nervous system (PNS) structures: Cranial nerves and branches Spinal nerves and branches Ganglia Sensory receptors Copyright 2010, John Wiley & Sons, Inc. Organization of the Nervous System Copyright 2010, John Wiley & Sons, Inc. Organization of the Nervous System Peripheral nervous system (PNS) divisions Somatic (SNS) Sensory neurons from head, body wall, limbs, special sense organs Motor neurons to skeletal muscle: voluntary Autonomic (ANS) nervous systems Sensory neurons from viscera Motor neurons to viscera (cardiac muscle, smooth muscle, glands): involuntary Sympathetic: “fight-or-flight” Parasympathetic: “rest-and-digest” Enteric nervous system (ENS): “brain of the gut” Copyright 2010, John Wiley & Sons, Inc. Organization of the Nervous System Peripheral nervous system (PNS), Enteric nervous system (ENS): “brain of the gut” Sensory neurons monitor chemical changes and stretching of GI wall Motor neurons regulate contractions, secretions and endocrine secretions (involuntary) Copyright 2010, John Wiley & Sons, Inc. Structure and Function of the Nervous System Interactions Animation Introduction to Structure and Function of the Nervous System You must be connected to the internet to run this animation. Copyright 2010, John Wiley & Sons, Inc. Action Potentials Action potentials = nerve impulses Require A membrane potential: a charge difference across cell membrane (polarization) Ion channels: allow ions to move by diffusion from high to low concentration Leakage channels: allow ions to leak through membrane; there are more for K+ than for Na+ Gated channels Open and close on command Respond to changes in membrane so can generate and conduct action potentials Copyright 2010, John Wiley & Sons, Inc. Resting Membrane Potential Typically –70 mV Inside of membrane more negative than outside Caused by presence of ions: Inside (more negative) because cytosol has: Many negative ions (too large to leak out): amino acids (in cellular proteins) and phosphates (as in ATP) K+ that easily leaks out through many K+ channels Outside (more positive) because interstitial fluid has: Few negative ions Na+ that does not leak out of cell: few Na+ channels Membrane “pumps” that quickly pump out Na+ that does leak (diffuse) into cell Copyright 2010, John Wiley & Sons, Inc. Resting Membrane Potential Copyright 2010, John Wiley & Sons, Inc. Action Potential Series of events that activate cell membrane in neuron or muscle fiber An initial event (stimulus) is required Triggers resting membrane to become more permeable to Na+ Causes enough Na+ to enter cell so that cell membrane reaches threshold (~ –55 mv) If so, the following events occur: action potential which spreads along neuron or muscle fiber Copyright 2010, John Wiley & Sons, Inc. Action Potential Depolarizing phase Na+ channels open as more Na+ enters cell, membrane potential rises and becomes positive (–70 0 + 30 mv) Repolarizing phase K+ channels open as more K+ leave cell, membrane potential is returned to resting value (+ 30 0 –70 mv) May overshoot: hyperpolarizing phase Typically depolarization and repolarization take place in about 1 millisecond (1/1000 sec) Copyright 2010, John Wiley & Sons, Inc. Action Potential Copyright 2010, John Wiley & Sons, Inc. Key events of action potential Action Potential Recovery Levels of ions back to normal by action of Na+/K+ pump Refractory period (brief): even with adequate stimulus, cell cannot be activated All-or-none principle If a stimulus is strong enough to cause depolarization to threshold level, the impulse will travel the entire length of the neuron at a constant and maximum strength. Copyright 2010, John Wiley & Sons, Inc. Membrane Potentials Interactions Animations Membrane Potentials You must be connected to the internet to run this animation. Copyright 2010, John Wiley & Sons, Inc. Conduction of Nerve Impulses Nerve impulse conduction (propagation) Each section triggers the next locally as even more Na+ channels are opened (like row of dominos) Types of conduction Continuous conduction Saltatory conduction In unmyelinated fibers; slower form of conduction In myelinated fibers; faster as impulses “leap” between nodes of Ranvier Factors that increase rate of conduction Myelin, large diameter and warm nerve fibers Copyright 2010, John Wiley & Sons, Inc. Conduction of Nerve Impulses Copyright 2010, John Wiley & Sons, Inc. Conduction of Nerve Impulses Copyright 2010, John Wiley & Sons, Inc. Synaptic Transmission Similar sequence of events occurs at Synapse (neuron-neuron) Neuromuscular junction (neuron-muscle fiber: chapter 8) Neuroglandular junction (neuron-gland) Triggered by action potential (nerve impulse) Components of synapse: Sending neuron: presynaptic neuron (releases neurotransmitter) Space between neurons: synaptic cleft Receiving neuron: postsynaptic neuron Copyright 2010, John Wiley & Sons, Inc. Synaptic Transmission Action potential arrives at presynaptic neuron’s end bulb Opens voltage gated Ca2+ channels Ca2+ flows into presynaptic cytosol Increased Ca2+ concentration exocytosis of synaptic vesicles Neurotransmitter (NT) released into cleft NT diffuses across cleft and binds to receptors in postsynaptic cell membrane Copyright 2010, John Wiley & Sons, Inc. Synaptic Transmission NT serves as chemical trigger (stimulus) of ion channels Postsynaptic cell membrane may be depolarized or hyperpolarized Depends on type of NT and type of postsynaptic cell 1000+ neurons converge on synapse; the sum of all of their NTs determines effect If threshold reached, then postsynaptic cell action potential results Copyright 2010, John Wiley & Sons, Inc. Synaptic Transmission One-way transmission only because Only presynaptic cells release NT Only postsynaptic cells have receptors for NT binding Finally, NT must be removed from the cleft. Three possible mechanisms Diffusion out of cleft Destruction by enzymes (such as ACh-ase) in cleft Transport back (recycling) into presynaptic cell Copyright 2010, John Wiley & Sons, Inc. Signal Transmission at the Chemical Synapse Copyright Copyright 2010, 2009 John John Wiley Wiley & & Sons, Sons, Inc. Inc. 39 Diversity of Neurotransmitters About 100 substances that are either known or suspected neurotransmitters have been identified in the human body. Many neurotransmitters are amino acids or derivatives thereof. Some neurotransmitter are activating by depolarizing the post synaptic cell; they are excitatory Other neurotransmitter are inhibiting by hyperpolarizing the post synaptic cell; they are inhibitory Many important drugs are interfering with the biological function of neurotransmitters in the CNS Neurotransmitters Acetylcholine (ACh): common in PNS Amino acids Glutamate, aspartate, gamma aminobutyric acid (GABA), glycine Modified amino acids Stimulatory (on skeletal muscles) Inhibitory (on cardiac muscle) Norepinephrine (NE), dopamine (DA), serotonin Neuropeptides such as endorphins Nitric oxide (NO) Copyright 2010, John Wiley & Sons, Inc. Neurotransmitter inhibitors Neurotransmitter Acetylcholine (ACh) Mode of action excitatory/inhibitory - via either muscarinic (m) or nicotinic (n) receptors Interfering drugs / effects / disorders Inhibitors Curare (- AChR) --> at NMJ, Botox & local anesthetics (-) --> ACh release Atropin (- AChR) --> parasympaticus Parasympatomimetics Muscarin (+ AChR) --> parasympaticus Nicotine (+ AChR) --> vegetative ganglia & NMJ Carbachol (+) --> ACh mimetic Pilocarpin (+) --> ACh mimetic Norepinephrine (Nor) excitatory Isoprotenerol (+) -stimulate the α1, α2, β1 and β2 Propranolol (-) --> beta-receptors (heart) Adrenaline (Adr) adrenoceptors; Phentolamine (-) --> alpha-receptors (blood vessels) Glutamate excitatory (NMDA-Receptor) Aspartate excitatory gamma amino butyric acid (GABA)inhibitory Diazepam ("Valium") (+) Glycine inhibitory Dopamin (DA) excitatory Cocaine (+) - inhib. of reuptake Zyprexa (-) - inhib. of DA receptor binding Schizophrenia (excess DA) Chlorpromazine (-) Endorphins, Enkephalins excitatory Acupuncture (+) - stim. of analgesia Euphoria - "Runner's high" effect Serotonin excitatory Imipramine (+) Fluoxetine (+) - selective serotonin reuptake inhibitors (SSRIs) Sertraline (+) Nitric oxide (NO) excitatory (local neurotransmitter) Neurological Pathology – Disease & disorders affecting nerves Neurology = branch of medical sciences that deals with the normal functioning and disorders of the nervous system Polyneuritis = Inflammatory neurodegenerative disorder characterized by the degeneration of myelin sheaths due to chronic lack of vitamin B1 (thiamin); affected patients show impaired reflexes SSRI = selective serotonin re-uptake inhibitors; molecules, such as fluoxetine (Prozac) or sertaline that selectively block the re-uptake of the excitatory neurotransmitter serotonin from the synaptic gap; they block the binding of serotonin to the serotonin transporter; commonly administered to patients for treatment of depression and other mood disorders Prozac (fluoxetine) The most commonly used anti-depressant in the U.S.; class of SSRIs which targets the transporter protein (5-HTT) of the neurotransmitter serotonin in brain; in presence of Prozac, the excitatory neurotransmitter serotonin remains longer in synaptic gap Multiple sclerosis (MS) = progressive, inflammatory disease of the CNS; caused by the entering of white blood cells into the brain and their subsequent destruction of the axon-surrounding myelin sheaths; more prevalent in females than in males; affects about 2 million people worldwide; cause is unknown, but there seems to be a connection to previous viral infection of the CNS, e.g. by the herpes virus; DEET = popular synthetic insect repellent, which is used by an estimated 200 million people worldwide; according to a recent study it is suspected to cause CNS damaeg the same way as some insecticides and nerve gases, e.g. sarin, do. Acetylcholinesterase enzyme inhibitor. NMDA ("Ecstasy") = Synthetic acetoamphetamine derivative; transient euphoria-triggering, illegal "fashion drug", which strongly affects the serotonin system of the CNS; leads to serotonin increase in the synaptic gaps due to interfering with the serotonin transporter/ 5-HTT uptake system; Ecstasy & Toxicology “Animal studies strongly suggest that NMDA inflicts lasting damage to the brain's serotonin system. According to an UK long-term effect study, people who took ecstasy performed worse on mental performance tests, e.g. memory, attention, planning, showed deficiencies in verbal and working memory tests, showed signs of depression and a weakened immune system.” End of Chapter 9 Copyright 2010 John Wiley & Sons, Inc. All rights reserved. Reproduction or translation of this work beyond that permitted in section 117 of the 1976 United States Copyright Act without express permission of the copyright owner is unlawful. Request for further information should be addressed to the Permission Department, John Wiley & Sons, Inc. The purchaser may make back-up copies for his/her own use only and not for distribution or resale. The Publishers assumes no responsibility for errors, omissions, or damages caused by the use of theses programs or from the use of the information herein. Copyright 2010, John Wiley & Sons, Inc.