MUSCLE TISSUE Dept. Histology & Embryology Faculty of Medicine MU pvanhara@med.muni.cz Petr Vaňhara, PhD Výsledek obrázku pro skeletal muscle fluorescence Epithelium Muscle Nerve Connective Based on morphology and function: Cytoskeleton à contraction Mesoderm – skeletal muscle, myocard, mesenchyme – smooth muscles Rarely ectoderm (eg. m. sphincter a m. dilatator pupillae) Neurons and neuroglia Reception and transmission of electric signals Ectoderm, rarely mesoderm (microglia) Dominant extracellular matrix Connective tissue, cartilage, bone… Mesenchyme Continual, avascular layers of cells with different functions, oriented to open space, with specific junctions and minimum of ECM and intercellular space. Derivates of all three germ layers http://www.arthursclipart.org/medical/humanbody/muscle%20tissue.gif http://djpowell.files.wordpress.com/2009/02/neuron-network.jpg http://www.technion.ac.il/~mdcourse/274203/slides/Connective%20%20Tissue/2-Loose%20Connective%20Tis sue-A.jpg http://www.temple.edu/dentistry/admissions/Images/epithelium.jpg CONTEMPORARY TISSUE CLASSIFICATION •Hallmarks §Unique cell architecture §Excitability and contraction §Mesodermal origin • • GENERAL CHARACTERISTIC OF MUSCLE TISSUE Striated skeletal Striated cardiac Smooth MUSCLE TISSUE Výsledek obrázku pro popeye http://www.med.muni.cz/histol/MedAtlas_2/img_1024x768/OH_img6-1.jpg STRIATED SKELETAL MUSCLE TISSUE -Composition: muscle cells + connective tissue, blood vessels -Unique cell architecture – long multinuclear cells – muscle fibers (rhabdomyocytes) -Long axis of cells is oriented parallel with direction of contraction -Specific terminology: •cell membrane = sarcolemma •cytoplasm = sarcoplasm •sER = sarcoplasmic reticulum •Muscle fiber – microscopic unit of skeletal muscle •Myofibril – LM unit – myofilaments – unit of muscle fibers •Myofilaments – filaments of actin and myosin (EM) HISTOLOGY OF SKELETAL MUSCLE TISSUE Image285 Svalová tkáň - 1 Kosterní svalovina musske skmusadi STRUCTURE OF SKELETAL MUSCLE http://www.iupui.edu/~anatd502/Labs.f04/muscle%20lab/muscle%20CT%20coats%20schematic.jpg -Endomysium – around each muscle cell (fiber) -Perimysium – around and among the primary bundles of muscle cells -Epimysium – dense irregular collagen c.t., continuous with tendons and fascia -Fascia – dense regular collagen c.t. • http://faculty.etsu.edu/forsman/Histology%20of%20musclefor%20web_files/image011.jpg -Containment -Limit of expansion of the muscle -Transmission of muscular forces CONNECTIVE TISSUE OF SKELETAL MUSCLE CONNECTIVE TISSUE OF SKELETAL MUSCLE EM006b image1 EM007b CONNECTIVE TISSUE OF SKELETAL MUSCLE SouvisejÃcà obrázek ORGANIZATION OF SKELETAL MUSCLE TISSUE WHY IS SKELETAL MUSCLE TISSUE STRIATED? -morphological and functional unit: muscle fiber (rhabdomyocyte) – elongated, cylindrical-shaped, multinucleated cell (syncytium) -nuclei are located at the periphery (under sarcolemma) -myofibrils show cross striation -diameter of muscle fiber: 25-100 mm -length: millimeters - centimeters (up to 15) STRUCTURE OF SKELETAL MUSCLE •Myosin heavy chain (MHC) type I and II -distinct metabolic, contractile, and motor-unit properties -ATPase activity •Twitch type -Fast vs. slow •Fiber color -Red vs. white •Myoglobin content •Glycogen content •Energy metabolism •Endurance - http://upload.wikimedia.org/wikipedia/commons/thumb/b/b7/Denervation_atrophy_-_atp94_-_intermed_mag .jpg/1920px-Denervation_atrophy_-_atp94_-_intermed_mag.jpg https://lazyhclimbingclub.files.wordpress.com/2012/09/muscle-fiber-types.jpg CLASSIFICATION OF SKELETAL MUSCLE Properties Type I fibers Type IIA fibers Type IIX fibers Motor Unit Type Slow Oxidative (SO) Fast Oxidative/Glycolytic (FOG) Fast Glycolytic (FG) Twitch Speed Slow Fast Fast Twitch Force Small Medium Large Resistance to fatigue High High Low Glycogen Content Low High High Capillary Supply Rich Rich Poor Myoglobin High High Low Red Color Dark Dark Pale Mitochondrial density High High Low Capillary density High Intermediate Low Oxidative Enzyme Capacity High Intermediate-high Low Z-Line Width Intermediate Wide Narrow Alkaline ATPase Activity Low High High Acidic ATPase Activity High Medium-high Low CLASSIFICATION OF SKELETAL MUSCLE •Muscle fiber = myofiber = syncitium = rhabdomyocyte •Muscle fiber – morphological and functional unit of skeletal muscle [Ø 25 – 100 mm] •Myofibrils – compartment of fiber sarcoplasm [Ø 0.5 – 1.5 mm] •Sarcomere – the smallest contractile unit [2.5 mm], serial arrangement in myofibrils •Myofilaments – actin and myosin, are organized into sarcomeres [Ø 8 and 15 nm] • Muscle_Cell_Close-up_1 Sarcomere ULTRASTRUCTURE OF RHABDOMYOCYTE T-tubule terminal cisterna mitochondria myofibrils sarcolemma Sarcolemma + t-tubules, Sarcoplasm: Nuclei, Mitochondria, Golgi apparatus, Glycogen (b granules) Sarcoplasmic reticulum (smooth ER) – reservoir of Ca2+ Myofibrils (parallel to the length of the muscle fiber) tubules + cisternae of sER ULTRASTRUCTURE OF RHABDOMYOCYTE -elongated structures [Ø 0.5 – 1.5 m] in sarcoplasm of muscle fiber oriented in parallel to the length of the fiber, MuscleSarcomere -Actin + myosin myofilaments -Sarcomere -Z-line -M-line and H-zone -I-band, A-band muscle3 myogeom MYOFIBRILS MYOFIBRILS http://apbrwww5.apsu.edu/thompsonj/Anatomy%20&%20Physiology/2010/2010%20Exam%20Reviews/Exam%203%20R eview/09-03bc_skelemusfi_1.jpg SARCOMERE Imag108 A–band I–band ½ I-band H-zone SARCOMERE sarcomere-e SARCOMERE 179 019852403x •Terminal cistern •T-tubule •Terminal cistern • TRIAD •T-tubules (“T” system ) are invaginations of sarcoplasm and bring action potential to terminal cisternae change permeability of membrane for CaII+ ions • SARCOPLASMIC RETICULUM emmodel SARCOPLASMIC RETICULUM https://s-media-cache-ak0.pinimg.com/736x/13/d8/fb/13d8fb80fa4169d09365bbbdec8c07a9.jpg ULTRASTRUCTURE OF RHABDOMYOCYTE •Fibrilar actin (F-actin), (Æ 7 nm, «1 mm) • • •Tropomyosin – thin double helix in groove of actin double helix, spans 7 monomers of G-actin •Troponin – complex of 3 globular proteins •TnT (Troponin T) – binds tropomyosin •TnC (Troponin C) – binds calcium •TnI (Troponin I) inhibits interaction between thick and thin filaments Subversion of the actin cytoskeleton during viral infection external image TN1a.jpg THIN MYOFILAMENTS http://163.178.103.176/Tema1G/Grupos1/GermanT1/GATP20/e2_files/7no5.gif •Myosin II • -Large polypeptide, golf stick shape, (Æ 15 nm, «1,5 mm) -Bundles of myosin molecules form thick myofilament http://www.aps.uoguelph.ca/~swatland/HTML10234/LEC11/PS50.gif •Nebulin -600-900kDa -F-actinu stabilization - •Titin ->MDa -Myosin II stabilization Výsledek obrázku pro nebulin THICK MYOFILAMENTS http://upload.wikimedia.org/wikipedia/commons/thumb/6/6e/Sarcomere.svg/1350px-Sarcomere.svg.png MYOFILAMENTS ASSEMBLE TO CONTRACTIVE STRUCTURES -Propagation of action potential (depolarization) via T-tubule (= invagination of sarcolemma) -Change of terminal cisternae permeability – releasing of Ca+ ions increases their concentration in sarcoplasm -Myosin binds actin - sarcomera then shortens by sliding movement – contraction -Relaxation: repolarization, decreasing of Ca2+ ions concentration, inactivation of binding sites of actin for myosin • Imag110 myosin actin MYOFILAMENTS ASSEMBLE TO CONTRACTIVE STRUCTURES 1.Impulse along motor neuron axon 2.Depolarization of presynaptic membrane (Na+ influx) 3.Synaptic vesicles fuse with presynaptic membrane 4.Acetylcholine exocyted to synaptic cleft 5.Acetylcholine diffuses over synaptic cleft 6.Acetylcholine binds to receptors in postsynaptic membrane 7.Depolarization of postsynaptic membrane and sarcolemma (Na+ influx) 8.T-tubules depolarization 9.Depolarization of terminal cisternae of sER 10.Depolarization of complete sER 11.Release of CaII+ from sER to sarcoplasm 12.CaII+ binds TnC 13.Troponin complex changes configuration 14.Tropomyosin removed from actin-myosin binding sites 15.Globular parts of myosin bind to actin 16.ATPase in globular parts of myosin activated 17.Energy generated from ATP®ADP + Pi 18.Movement of globular parts of myosin 19.Actin myofilament drag to the center of sarcomere 20.Sarcomeres contract (H-zone, I-band shorten) 21.Myofibrils contracted 22.Muscle fiber contracted http://jessicaz.me.cmu.edu/molecular_data/NMJ_files/image002.jpg MECHANISM OF CONTRACTION [USEMAP] http://highered.mheducation.com/sites/0072495855/student_view0/chapter10/animation__breakdown_of_at p_and_cross-bridge_movement_during_muscle_contraction.html MECHANISM OF CONTRACTION Courtesy Dr. Pacherník, Faculty of Science MU Výsledek obrázku pro muscle proprioreceptor PROPRIORECEPTORS Výsledek obrázku pro muscle spindle TEM Golgiho tendon organs -myotendineous junction -senzory endings synapsed with inhibitory neurons -tension, stretch Muscle spindles -change in muscle elongation (stretch) -modified perimysium -thin muscle (intrafusal) fibers -sensory endings -reflexes, coordination of muscle groups http://www.embryology.ch/images/mimgmuskel/m2histogenese/musc_junction.jpg http://apbrwww5.apsu.edu/thompsonj/Anatomy%20&%20Physiology/2010/2010%20Exam%20Reviews/Exam%203%20R eview/neur-musc-junc.fig.9.8a.jpg 1 2 3 4 Myelinated axons Neuromuscular junction Capillaries Muscle fiber nucleus NEUROMUSCULAR JUNCTION NEUROMUSCULAR JUNCTION NEUROMUSCULAR JUNCTION http://www.chop.edu/sites/default/files/myasthenia-gravis-neuromuscular-junction-illustration-773x9 49.png http://www.chop.edu/sites/default/files/myasthenia-gravis-neuromuscular-junction-illustration-773x9 49.png MYASTHENIA GRAVIS Ptóza víček u myasténie gravis NEUROMUSCULAR JUNCTION Výsledek obrázku pro kurare Výsledek obrázku pro curare synapsis Curare Výsledek obrázku pro botulotoxin poisoning Výsledek obrázku pro botox alternativní popis obrázku chybí Botulotoxin Clostridium botulinum NEUROMUSCULAR JUNCTION https://classconnection.s3.amazonaws.com/456/flashcards/545456/png/costamere-141C2C681FD3C54184F.pn g •Structural components linking myofibrils to sarcolemma •Circumferential alignment • dystrophin-associated glycoprotein (DAG) complex •links internal cytoskelet to ECM •Integrity of muscle fiber COSTAMERES http://www.nature.com/nrm/journal/v10/n4/images/nrm2634-f1.jpg https://upload.wikimedia.org/wikipedia/commons/5/52/Costamere_structure_in_mouse_quadriceps_-_journ al.pone.0002604.g003-cropped.png COSTAMERES http://www.nature.com/nrg/journal/v14/n6/images/nrg3460-f1.jpg COSTAMERES https://www.researchgate.net/profile/Anders_Nedergaard/publication/230894835/figure/fig6/AS:2028394 70153739@1425372106375/This-figure-shows-the-structure-of-the-costamere-and-known-molecular-interac tions-Below.png COSTAMERES http://ajs.sagepub.com/content/33/5/745/F1.large.jpg COSTAMERES DUCHENNE MUSCULAR DYSTROPHY http://compbio.berkeley.edu/people/ed/rust/dys-gene.png http://neuromuscular.wustl.edu/pics/biopsy/dmd/dmdrevhe.jpg http://neuromuscular.wustl.edu/pics/biopsy/dmd/dmdrevdys2.jpg http://neuromuscular.wustl.edu/pics/biopsy/dmd/dystrophinwb.jpg Lane 1: Becker dystrophy; Dystrophin has reduced abundance but normal size. Lane 2: Becker dystrophy; Dystrophin has reduced size and abundance. Lane 3: Normal; Dystrophin has normal size and amount. Lane 4: Duchenne dystrophy; Almost no protein is present. http://neuromuscular.wustl.edu/pathol/dmdpath.htm COSTAMERES http://www.humanillnesses.com/original/images/hdc_0001_0002_0_img0183.jpg https://kin450-neurophysiology.wikispaces.com/file/view/timeline-DMD-patient.png/478191732/462x258/ timeline-DMD-patient.png COSTAMERES CARDIAC MUSCLE TISSUE MUSCLE TISSUE Výsledek obrázku pro romeo julia shakespeare Výsledek obrázku pro romeo julia shakespeare •made up of long branched fiber (cells) – cardiomyocytes, •cardiomyocytes are cylindrical cells, branched on one or both ends (Y, X shaped cells), •sarcoplasm: single nucleus in the center of cell, striated myofibrils, numerous mitochondria, •cells are attached to one another by end-to-end junctions – intercalated discs. HISTOLOGY OF CARDIAC MUSCLE TISSUE chains of cardiomyocytes blood capillary with erythrocytes Intercalated disc HISTOLOGY OF CARDIAC MUSCLE TISSUE cardiacmuscle heartmuscle1 HISTOLOGY OF CARDIAC MUSCLE TISSUE 4 C) cardiac muscle; 5. E) striations, branched fibers, central nuclei image1 arm8 ULTRASTRUCTURE OF CARDIOMYCYTE -no triads, but diads: 1 t-tubule + 1 cisterna -t-tubules around sarcomeres at Z lines rather than at zone of overlap -sarcoplasmic reticulum via its tubules contact sarcolemma as well as the t-tubules -cardiac muscle cells are totally dependent on aerobic metabolism to obtain the energy -large numbers of mitochondria in sarcoplasm and abundant reserves of myoglobin (to store oxygen) -abundant glycogen and lipid inclusions http://esciencenews.com/files/images/20080622204300.jpg http://medicalpicturesinfo.com/wp-content/uploads/2011/08/Cardiac-muscle-2.jpg CARDIAC MUSCLE COMPARED TO SKELETAL -fasciae adherentes (adhesion of cells) -nexus (quick intercellular communication – transport of ions, electric impulses, information) - „scalariform“ shape of cell ends - Muscle7 https://s-media-cache-ak0.pinimg.com/originals/ab/8c/4a/ab8c4abe938a777282f58e1acef9a46a.jpg http://www.cheaplasereye.com/wp-content/uploads/2014/05/intercalated-discs-gap-junctions.png INTERCALATED DISC A) Cardiac muscle nexus fascia adherens Intercalated disc: pure2 INTERCALATED DISC •Actin + myosin myofilaments •Sarcomere •Z-line •M-line and H-zone •I-band, A-band •T-tubule + 1 cisterna = diad (around Z-line) MuscleL1 MYOFIBRILS IN CARDIOMYOCYTE abdelaziz_html_m5d945a9f MYOFIBRILS IN CARDIOMYOCYTE ULTRASTRUCTURE OF CARDIOMYOCYTES PURKINJE FIBERS -are located in the inner layer of heart ventricle wall -are specialized cells fibers that conduct electrical stimuli or impulses that enables the heart to contract in a coordinated fashion -numerous sodium ion channels and mitochondria, fewer myofibrils Image:Purkinje fibers.jpg gr84 SPECIALIZED CARDIOMYOCYTES https://upload.wikimedia.org/wikipedia/commons/thumb/0/0b/ECG_Principle_fast.gif/220px-ECG_Principl e_fast.gif https://upload.wikimedia.org/wikipedia/commons/thumb/9/9d/Jan_Vil%C3%ADmek_-_Jan_Evangelista_Purkyn %C4%9B.jpg/225px-Jan_Vil%C3%ADmek_-_Jan_Evangelista_Purkyn%C4%9B.jpg ATRIAL CARDIOMYOCYTES Soubor:C-type natriuretic peptide.png •Natriuretic peptide A (ANP) •atrial cardiomyocytes •vasodilatation, diuresis SPECIALIZED CARDIOMYOCYTES SMOOTH MUSCLE TISSUE Výsledek obrázku pro smooth muscle cells MUSCLE TISSUE •Cells – leiomyocytes - form layers - eg. in walls of hollow organs B) Smooth muscle Crosssection Longitudinal image006 Výsledek obrázku pro oesophagus histology SMOOTH MUSCLE TISSUE •spindle shaped cells (leiomyocytes) with myofilaments not arranged into myofibrils (no striation), 1 nucleus in the centre of the cell •myofilaments form bands throughout the cell •actin filaments attach to the sarcolemma by focal adhesions or to the dense bodies substituting Z-lines in sarcoplasm •sarcoplasmic reticulum forms only tubules, CaII+ ions are transported to the cell via pinocytic vesicles •zonulae occludentes and nexuses connect cells •calmodulin http://download.e-bookshelf.de/download/0000/6653/27/L-X-0000665327-0001397099.XHTML/images/c04uf00 1.jpg SMOOTH MUSCLE TISSUE Caveolae •caveolae are equivalent to t-tubules •transmembrane ion channels image1 CAVEOLS Výsledek obrázku pro caveolin smooth muscle cells Výsledek obrázku pro caveolin smooth muscle cells CAVEOLS SmoothMuscle Smooth Muscle + nexuses CONTRACTION OF LEIOMYCYTES https://universalchangegroup.files.wordpress.com/2014/09/muscle-cells.jpg INNERVATION OF LEIOMYCYTES http://www.austincc.edu/rfofi/NursingRvw/NursingPics/MusclePics/Picture36.jpg http://www.austincc.edu/rfofi/NursingRvw/NursingPics/MusclePics/Picture37.jpg http://www.austincc.edu/rfofi/NursingRvw/NursingPics/MusclePics/Muscle_clip_image016.jpg CONTRACTION OF LEIOMYCYTES SMOOTH MUSCLE TISSUE Hallmark Skeletal muscle Cardiac muscle Smooth muscle Cells Thick, long, cylindrical, non-branched Branched, cylindrical Small, spindle-shaped Nuclei Abundant, peripherally 1-2, centrally 1, centrally Filaments ratio (thin:thick) 6:1 6:1 12:1 sER and myofibrils Regular sER around myofibrils Less regular sER, myofibrils less apparent Less regular sER, myofibrils not developed T tubules Between A-I band, triads Z lines, diads Not developed Motor end plate Present Not present Not present Motor regulation Voluntary control No voluntary control No voluntary control Other Large multinucleated cells in bundles, c.t. Intercalated discs, working and specialized cardiomyocytes Caveoli, overlapping cells in layers SUMMARY EMBRYONIC DEVELOPMENT OF MUSCLE SYSTEM Výsledek obrázku pro somites fluorescence Výsledek obrázku pro myotomes embryo EMBRYONIC DEVELOPMENT OF MUSCLE SYSTEM http://cshperspectives.cshlp.org/content/4/2/a008342/F1.large.jpg EMBRYONIC DEVELOPMENT OF MUSCLE TISSUE Výsledek obrázku pro limb muscles development AER LIMB MUSCLES Výsledek obrázku pro TRUNK MUSCLES EMBRYONIC DEVELOPMENT Výsledek obrázku pro muscles trunk embryo Deep back muscles Intercostal muscles Surface back muscles: limb origin Spinocostal muscles http://cshperspectives.cshlp.org/content/4/2/a008342/F1.large.jpg TRUNK MUSCLES TRUNK MUSCLES Výsledek obrázku pro prune belly syndrome PRUNE BELLY SYNDROME •Absence of abdominal muscles •Failure of hypaxial specification •VACTERL and aneuploidy association Cross section of standard fish.svg •V - Vertebral anomalies •A - Anorectal malformations •C - Cardiovascular anomalies •T - Tracheoesophageal fistula •E - Esophageal atresia •R - Renal (Kidney) and/or radial anomalies •L - Limb defects EMBRYONIC DEVELOPMENT OF SKELETAL MUSCLE TISSUE http://image.slidesharecdn.com/ch10muscletissue-140721070554-phpapp01/95/ch10-muscle-tissue-65-638. jpg?cb=1405944451 http://cshperspectives.cshlp.org/content/4/2/a008342/F3.large.jpg REGENERATION http://www.intechopen.com/source/html/43847/media/image3.jpeg REGENERATION http://www.intechopen.com/source/html/18233/media/image3.jpeg DIFFERENTIATION IN VITRO Výsledek obrázku pro fibroblasts Výsledek obrázku pro ips on matrigel http://www.nature.com/nmat/journal/v11/n10/images_article/nmat3438-f1.jpg TISSUE ENGINEERING https://www.nature.com/news/artificial-jellyfish-built-from-rat-cells-1.11046 https://www.nature.com/articles/nbt.2269 BREAK 5 min. Image result for coffee break Nerve tissue Brno, April 2020 •Nerve tissue •Neuron •Synapse •Neuroglia •Nerve •Saltatory signal propagation •Development of nerve tissue •Nerve regeneration Lecture 9 Nerve tissue – general 1 Controls and integrates all body activities within limits that maintain life Key functions 1. •sensing changes with sensory receptors • •interpreting and remembering those changes • •reacting to those changes with effectors 48-01-VertebNervousSys-NL.gif 000784A6Macintosh HD BC4DC1A3: Somatic X Autonomous (vegetative) Anatomical organization of nervous system 1 Central nervous system - CNS Definition: Unpaired, bilaterally symmetrical structures extending along the longitudinal axis of the midsagittal plane of the body. Structures arising directly from the neural tube. Includes: •Brain •Spinal cord Peripheral nervous system - PNS Definition: Made up of transmission pathways carrying information between the CNS and external/internal environments. Afferent (sensory) pathways: Carry information to the CNS. Efferent (motor) pathways: Carry information from the CNS. Includes: •Cranial nerves (12 pairs) •Spinal nerves (31 pairs) •Peripheral nerves •Ganglia 08_06-AnatOrgNervousSys_L Anatomical organization of nervous system 2 Nerve tissue – General – Neuron 1 Nervová tkáň - 1 Typy neuronů Nervous tissue is made up of just 2 types of cells: •Neurons •Neuroglia - glial cells (supporting cells) •Neurons are the basic functional units of nervous tissue. •They are highly specialized to transmit nerve impulses. • • • Neuron 2 1.Perikaryon (neurocyte) 2.Processes: (one-way signal conduction) - axon (always only one; centrifugal conduction) - dendrit(es) (centripetal conduction) 173826 48-00x1-AplysiaNeurons.jpg 000784A6Macintosh HD BC4DC1A3: Neuron 3 - Perikaryon Position: CNS – grey matter PNS – ganglia Shape: pyramidal, shpherical, ovoid, peer-shaped Size: 5 to 150 mm Organelles: •Nuclues – large + pale + prominent nucleoli •Nissl substance – rough ER •Neurofibrils (neurofilaments + neurotubules + actin) •Lipofuscin pigment clumps Image006 Neuron 4 - Perikaryon Cell and Tissue Ultrastructure – A Functional Perspective; 1993; Cross and Mercer, Freeman and Co.; Page 127 Nissl substance in TEM Neuron 5 - Perikaryon > Nissl body Neurofibril H-E stains Silver nitrate Neuron 6 - Perikaryon 91 lipofuscine granules Cilium derived from unused centriole Neuron 7 – Neurites / Processes 92 Dendrites Collaterals Axon (axon branching, telodendria) Neuron 7 – Neurites / Processes Axon (nerve fiber) Dendrites •Conducts impulses towards the cell body • •Typically short, highly branched & unmyelinated • •Surfaces specialized for contact with other neurons • •Contains neurofibrils & Nissl bodies •Receptive surface for synaptic junctions • •Contain MAP-2 (distinction from axon) • •Tens of thousands of synapses on large dendrites • •Dendritic spines located on surface of some dendrites • •Spines diminish with age and poor nutrition •1 axon projects from cell body at axon hillock • •Axon hillock - pyramid shaped region of the soma that is devoid of RER • •Some axons are up to 100 cm • •Initial segment = Spike trigger zone (a portion of axon from its origin to the beginning of myelin sheath) • •At spike trigger zone trigger zone summation of excitatory and inhibitory impulses occurred • •Collateral branches, Terminal arbor • •Myelinated or Unmyelinated • •Conduct impulses away from cell body • •Swollen tips called synaptic knob (terminal button) contain synaptic vesicles filled with neurotransmitters • •Cell membrane = axolemma • •Cytoplasm = axoplasm White matter: areas of myelinated axons Gray matter: areas of unmyelinated axons, cell bodies, and dendrites Neuron 8 – Neurites / Processes Neuron in TEM Axon hilloc Neuron 9 – Axonal transport •Slow transport: 1-5 mm/day • •Fast transport: 200-400 mm/day Why? many proteins made in soma must be transported to axon and axon terminal to repair axolemma, serve as gated ion channel proteins, as enzymes or neurotransmitters How? axonal transport – two-way passage of proteins, organelles, and other material along an axon •anterograde transport – movement down the axon away from soma (dynein) •retrograde transport – movement up the axon toward the soma •(kinesin) Nerve tissue – Neuropil 1 96 pyramidal cells - impregnation motoneurons - HE motoneurons – combined method All the material filling space among the bodies of neurons and glial cells + ECM Nerve tissue – Neuropil 2 97 C:\Documents and Settings\Sedláčková.HIST4\Dokumenty\cortex cerebri potkan\999008a\999008_a ko cortex cerebri-06.JPG Neuropil in TEM Neuron – Classification 1 According to the number of the processes Multipolar several dendrites & one axon (most common cell type) Bipolar one main dendrite & one axon (in retina, vestibular and cochlear ganglion) Unipolar (pseudounipolar) one process only (develop from a bipolar) (always sensory, in spinal ganglia) [USEMAP] 99 Neuron – Classification 2 According to the function Motor (efferent) neurons: •conduct impulses to muscles, neurons, glands Sensory (afferent) neurons: •receive sensation Interneurons: •local circuit neurons Synapse 1 Definition Synapses are highly specialized intercellular junctions, which link the neurons of each nervous pathway •Axon terminal forms bouton terminal • •Presynaptic membrane - contains mitochondria, and an abundance of synaptic vesicles with neurotransmitter • •Presynaptic dense projections - are associated with synaptic vesicles form active sites of synapse • •Synaptic vesicles (smaller + larger – storage) •Postsynaptic membrane - contains receptors and some dense materials • •Synaptic cleft - 20-30 nm width, occupied by fine filaments • •Glial cells increase synaptic efficacy • •Asymmetric synapses are excitatory (a thick postsynaptic membrane and a 30 nm synaptic cleft) • •Symmetric synapses are inhibitory (thin postsynaptic membrane and a 20 nm synaptic cleft) • • Need special staining to see by light microscopy Synapse 2 Inhibitory synapses •postsynaptic Cl- (or other anion) channels open •influx of anions •hyperpolarizition of membrane of postsynaptic neuron Excitatory synapses •postsynaptic Na+ channels open •influx of Na+ •depolarizition of membrane of postsynaptic neuron X Neurotransmitters •Acetylcholine • •Amioacids – gluatamate, glycin, GABA (gamma-amminobutyric acid) • •Monoamines – serotonin, catecholamines, dopamine, adrenaline, … • •Neuropeptides – enkefalin, somatostatin, neurotensin, …. • •Others – adenosine, nitric oxide Synapse 3 102 Synapse 4 103 C:\Documents and Settings\Sedláčková.HIST4\Dokumenty\cortex cerebri potkan\999012A\999012A cortex cerebri-25.JPG C:\Documents and Settings\Sedláčková.HIST4\Dokumenty\cortex cerebri potkan\999013A\999013A cortex-07.JPG Synapse in TEM Synapse 5 Classification according to the constitution Note: Neuromuscular junction – synapse between neuron and effector muscle fibre Axodendritic Axosomatic Axoaxonic Synapse 7 48-02-VertNeuronStruct-NL.jpg 000784A6Macintosh HD BC4DC1A3: One neuron may have 1 000 to 10 000 synapses !!! 48-13b-IntegraSynapticInput.jpg 000784A6Macintosh HD BC4DC1A3: Neuroglia General features •non-neuronal cells of several types •support and protect the neurons •bind neurons together and form framework for nervous tissue •in fetus, guide migrating neurons to their destination •if mature neuron is not in synaptic contact with another neuron it is covered by glial cells •prevents neurons from touching each other •gives precision to conduction pathways •only nuclei visible by light microscopy without special staining •there are several glial cells for each neuron Number of neurons: about 100 billions to 1 trillion Number of glial cells: 50x more then neurons Central neuroglia •Astrocytes •Oligodendrocytes •Microglia •Ependymal cells Peripheral neuroglia •Schwann cels •Satelite cells Neuroglia - Astrocytes Image015 Membrana limitans gliae… …superficialis …perivascularis •most abundant glial cell in CNS •covers entire brain surface and most non-synaptic regions of the neurons in the gray matter of the CNS •diverse functions: üform a supportive framework of nervous tissue ühave extensions (perivascular feet) that contact blood capillaries that stimulate them to form a tight seal called the blood-brain barrier üconvert blood glucose to lactate and supply this to the neurons for nourishment ünerve growth factors secreted by astrocytes promote neuron growth and synapse formation ücommunicate electrically with neurons and may influence synaptic signaling üregulate chemical composition of tissue fluid by absorbing excess neurotransmitters and ions üastrocytosis or sclerosis – when neuron is damaged, astrocytes form hardened scar tissue and fill space formerly occupied by the neuron ücontains GFAP Neuroglia - Astrocytes protoplasmic astrocyte fibrous astrocyte capillary perivascular foot (predominant in grey matter) (predominant in white matter) Neuroglia - Oligodendrocytes üsmaller than astrocytes; darker, round nucleus, abundant RER, well developed golgi apparatus üform myelin sheaths in CNS üone cell serves more then one axon ücannot migrate around axons (unlike Schwann cells) must push newer layers of myelin under the older ones so myelination spirals inward toward nerve fiber ünerve fibers in CNS have no Schwann sheath (neurilemma) or endoneurium üeach arm-like process wraps around a nerve fiber forming an insulating layer that speeds up signal conduction üdamaged in multiple sclerosis oligodendrocyte Neuroglia - Microglia üsmallest neuroglial cell üsmall, dark, elongated nuclei üpossess phagocytotic properties üwhen activated – antigen presenting cell üoriginate in bone marrow (mesodermal origin) Neuroglia – Ependymal cells üline ventricles of CNS and central canal of spinal cord ücuboidal or low columnar shape üno basal lamina üsecrete cerebrospinal fluid (CSF) üsome are ciliated, facilitate movement of CSF üparticipate in formation of Choroid plexus Nervová tkáň - 33 Ependym Neuroglia – Central - Summary Copyright © The McGraw-Hill Companies, Inc. 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Ependymal cell Cerebrospinal fluid Neurons Astrocyte Perivascular feet Microglia Oligodendrocyte Capillary Myelinated axon Myelin (cut) Neuroglia in PNS – Schwann cells 1 •cells that encircle all axons in PNS •provide structural and metabolic support to axons •provide guidance for axonal growth X Small diameter axons Enveloping by only cytoplasm Large diameter axons Wrapping by myelin sheaths only Schwann sheath – gray nerve fiber Schwann + myelin sheath– double contoured nerve fiber Neuroglia in PNS – Schwann cells 2 Neuroglia in PNS – Schwann cells 3 005 Small diameter axons Non-myelinated fibers One Schwann cell can ensheath multiple axons (typical for autonomous nerve system) only Schwann sheath – gray nerve fiber Neuroglia in PNS – Schwann cells 4 Myelination •begins 14th week of development •proceeds rapidly during infancy •completed in adolescence Large diameter axons Myelinated fibers Mesaxon Myelin sheath Neuroglia in PNS – Schwann cells 5 Schwann sheath + Myelin sheath Double contoured nerve fiber = Neurilemma Neuroglia in PNS – Schwann cells 6 Myelin sheath is segmented = Many Schwann cells are needed to cover one nerve fibre Schmidt-Lanterman clefts - Schwann cell cytoplasm trapped within the lamellae of myelin Internode 200 – 1500 mm Neuroglia in PNS – Schwann cells 7 Schmidt-Lanterman clefts Neuroglia – Functional effect of myelination 0356_0001 Signal propagation Saltatory (salta=jump) Non-myelinated axons – slow (0.5 – 2 m/s) Myelinated axons – fast (15 – 20 m/s) Peripheral nerve – Organization 1 Connective tissue layers composing nerves: •Endoneurium - surrounds axons •Perineurium - surrounds fascicles •Epineurium - surrounds the entire nerve Neurilemma Consists of 100’s to 100,000’s of myelinated and unmyelinated axons (nerve fibers). Peripheral nerve – Organization 2 epineurium perineurium endoneurium Peripheral nerve – Organization 3 perineurium endoneurium Axony s myelinovou pochvou Gastrulation Formation of the three germ layers •Ectoderm: outside, surrounds other layers later in development, generates skin and nervous tissue. •Mesoderm: middle layer, generates most of the muscle, blood and connective tissues of the body and placenta. •Endoderm: eventually most interior of embryo, generates the epithelial lining and associated glands of the gut, lung, and urogenital tracts. Nerve tissue – Development 1 Nerve tissue – Development 2 Neural Induction In addition to patterning the forming mesoderm, the primitive node also sets up the neural plate Endoderm + Mesoderm BMP-4 Ectoderm to Skin Primitive node BMP-4 antagonists Ectoderm to Nerve tissue noggin chordin follistatin X Nerve tissue – Development 3 ~AUT0008 Neurulation Folding and closure of the neural plate •neural folds close • •neural crest delaminates and migrates away • •closure happens first in middle of the tube and then zips rostrally and caudally • •anterior neuropore closes around day 25 • •posterior neuropore closes around day 28 Nerve tissue – Development 4 The early neural tube is a pseudostratified epithelium •The “apical” portion abuts the central canal •The “basal” portion abuts the surrounding tissue (e.g. somites, notochord, etc.). •Cell division occurs in the apical portion. S G2 M G0 G1 Nerve tissue – Development 5 Neural crest the “4th germ layer” C:\Users\Matt Velkey\Documents\TEACHING\EMBRYOLOGY\embryoImages\LangmansEmbryo-11thEd-figures\chapter06\jpg\Figur e 6-05.jpg Signals from: •Mesoderm •Adjacent skin •Neural plate Neural crest cells •Down-regulate cadherin •Delaminate from neuroepithelium •Transform into migratory mesenchymal cells •Give rise to many cell types Nerve tissue – Development 5 Neural crest derivatives Nerve tissue regeneration - CNS Stem / progenitor cells resiging in some areas of adult brain Life-long plasticity of CNS •Sprouting new dendrites •Synthesis of new proteins •Changes of synaptic contacts Nerve tissue regeneration - PNS Axons and dendrites may be repaired if: •Neuron cell body remains intact •Schwann cels remains active and form tube •Scar tissue does not form too rapidly injury Breakdown of axon Breakdown of myelin sheath Schwann cells divide Axon begins to grow (1.5 mm/day) Navigaion by Schwann cells Collaterals will die Thank you for your attention ! Questions and comments at: ahampl@med.muni.cz THANK YOU FOR ATTENTION pvanhara@med.muni.cz http://www.med.muni.cz/histology