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Basic neuroanatomy Characteristic of nervous tissue • Nervous tissue is specialized for intake, workabout and transfer of infos and that way coordinates most of the functions in the body • cells: – proper excitability neurons – Support cells (astrocytes, oligodendrocytes, microglia and ependymal cells) • Anatomically we divide nervous system into central (CNS – brain and medulla spinalis) and peripheral (PNS – nerves and ganglias) • In the CNS we distinguish gray and white matter • White matter visage is due to myelin – lipoprotein complex covering individual axons Classification of nervous tissue cells • Nervous tissue contains two types of cells: – neurons – major cells carrying informations – Glial cells (neuroglia, glia) (neuroglia) – provide support for neurons, protect them and participate in nutrition and function • • • • astrocytes (astrocytus) oligodendrocytes (oligodendrocytus) mikroglia (microgliocytus) Ependymal cells (ependymocytus) Neurons I • Are principal units of nervous tissue • Responsible for intake, workabout and transfer of signal • Composed of cell body (soma, perikaryon), dendrites (dendritum) and axon (axon) • Size of neurons vary in interval 5 µm (granular cells of cerebellum) to 150 µm (Purkynje cells of cerebellum) • After delivery no mitoses (not valid for hippocampal cells and bulbus olfactorius) • Wallerian neurodegeneration and neuroregeneration rules (axon and dendrite regenerate regularly, neuronal body only in several localities – dentate gyrus of hippocampus) Neurons II Neurons classification I • According to shape we divide neurons into: – multipolar (neuron multipolare) • More then 2 outlets (axon + dendrites) • Vast majority of neurons – bipolar (neuron bipolare) • Only 2 extensions (axon + dendrite) • retina, olfactory epithelium, ganglion n. vestibulocochlearis (VIII) etc. – pseudounipolar (neuron pseudounipolare) • Only 1 extension, subs. Splitting into dendrite and axon „T“ shaped • Sensory ganglia of spinal and cranial nerves – unipolar (neuron unipolare) • only 1 extension • Amacrine and horizontal cells of retina Neurons classification II Neurons classification III • From functional point we divide them into: – motor neurons (neuron motorium) • Controll effector organs (skeletal and smooth muscles; endocrine and exocrine glands) – sensory neurons (neuron sensorium) • Maintain infos intake from body and environment – interneurons (interneuron, neuron internuntiale) • Create complicated net between sensory and morot neurons Perikaryon (soma) I • Nucleus is big, ovoid and euchromatic with prominent nucleolus – great transcriptory activity • GER is rich and on surface it has numerous polyribosomes – together it forms so called Nissl substance • GA is located only in perikaryon and it gives rise to transport and secretory vesicules • mitochondrias are concentrated mostly in axonal hillocks and in pericaryon Perikaryon (soma) II • From cytoskeletal structures are important: – microtubules – maintain axonal transport (Hemeroff theory of quantuum states mediating quantuum information share in the matter) – neurofilaments – 10 nm thick intermediary filaments specific for nervous tissue – stained by silver or gold. • In the cytoplasm we may find also lipofuscin inclusions („pigment from wearing out“) or melanin Perikaryon (soma) III Dendrites • Are short extensions amplifying neuron surface enabling 1 neuron to receive infos from many neurons • In contrast to axon their width decreases with branching • At the synapsis there are dendritic spikes (its decrease is effect of chronic stress – Sapolsky et al.) • Cytoplasm of dendrites is almost equivalent to perikaryon, but no GA Dendritic spikes Dendritic spikes Axon I • Provides signal transduction from perikaryon and its further elaboration to other neuron or effector cell • neuron contains mostly 1 axon • At the origin is axonal hillock with no ribosomes or GER from perikaryon • In myelinized axons is between axonal hillock and origin of myelin sheet inicial segment (dense layer under axolemma in EM) – here originates action potencial Hillock and initial segment Axon II • axon is not branching for most of its course with exception of collateral branches returning into perikaryon • Branching happens at the terminal part of axon and each branch has synaptic ending – so called bouton terminaux • synaptic endings may be present during axonal course as boutons en passage Bouton terminaux Visual cortex, Macaque, Nature 2006 Axonal transport I • Due to missing GER is axon dependent of protein supply from perikaryon • Nutrition maintains axonal transport • Function of axonal transport is granted by specific microtubular organization – these function oas „railroad “ • „machine“ of carried particles (secretory vesicles with neuromediators, mitochondrias etc.) is molecular engine dynein and kinesin • There is axonal transport anterograde (from perikaryon) and retrograde (to perikaryon) Axonal transport II http://www.bio.unipd.it/~bubacco/html/body_lrrk2.html Synapse I • synapse (synapsis) is specialized structure for excitation transfer from on neuron to the other on (or on effector cell) • According to transfer variant we divide synapses into: – chemical (synapsis chemica): happens molecular secretion diffusing to target cell – electrical (synapsis electrica): cells are directly connected by nexus – depolarization propagates directly to target cell - rare Synapse II • According to location are synapses: – axodendritic (synapsis axodendritica) – most common – axosomatic (synapsis axosomatica) – axoaxonal – for example in presynaptic inhibition when carrying painful stimuli – dendritodendritic (synapsis dendritodendritica) – rare Synapse III Chemical synapse I • Three major subparts: – presynaptic membrane (membrana presynaptica) – cytoplasmatic membrane of axonal terminal – cytoplasm rich in secretory (synaptic) vesicules with neurotransmitter – synaptic cleft (fissura synaptica) – 20-30 nm wide (wider then between neuron and glia) – postsynaptic membrane (membrana postsynaptica) – cytoplasmatic membrane of target cell containing receptores for neurotransmitter Chemical synapse II • synaptic transfer has several phases: – Action potential after „arriving“ into synpase opens voltage gated Ca2+ channels – influx of Ca2+ into axonal teminal – Increased concentration of Ca2+ starts exocytosis of synaptic vesicles – Ca2+ is fast inactivated – pumped into ECT – Mediators from synaptic vesicles diffuse to target cell and react with its receptors – By reaction with receptors is indirectly changed permeability of post synaptic membrane for Na+, K+, Cl- or other ions – creation of excitatory post synaptic potential (EPSP) or inhibitory post synaptic potential (IPSP) • Synaptic delay is 0,3-0,5 s Chemical synapse III Neuromediators • Chemical substances at the connection between neurons or neuronsmuscles or other cells • acetylcholin • monoamines (noradrenalin, dopamin) • serotonin • GABA • glycin • Motor plate – presynaptic membrane of axon, synaptic cleft, postsynaptic membrane of muscle • substance P, neuropeptid Y Glial cells (neuroglia) • More numerous then neurons 10-50x, but due to smaller size form approx. 50 % of the CNS • „cooperate“ with neurons – offer support, nutrition, form myelin sheath of axons, phagocyte etc. • Staining by silver or gold impregnation and histochemical methods • Morphologically 4 types – astrocytes, oligodendrocytes, microglia and ependymal cells • After delivery may do mitosis Astrocytes I • Bigest neuroglial cells • Emanates numerous extensions (so colled vascular pedicles) covering blood vessels – Participate in hematoencephalic barrier • Contain numerous 10 nm thick intermediary filaments formed by glial fibrilal acidic protein (GFAP) • Offer neurons mechanical protection and help with metabolism • In case of injury astrocytes proliferate and form glial scar Blood-brain barrier (hematoencephalic barrier) Astrocytes II • Morphologically we recognize 2 types: – protoplasmic astrocytes • Numerous granulas in cytoplasm • Extensions are shorter and richly branching • Occur mostly in grey matter – Fibrilary astrocytes • Longer externsions w/o branching • Occur mostly in white matter Astrocytes III Astrocytes IV Oligodendrocytes I • Smaller compared to astrocytes and have less intermediary filaments • Form myelin sheath in the CNS – Perform same function as Schwann cells in PNS • Oligodendrocytes contain more axons at once (in contrast to Schwann cells) • Their number phylogenetically increases Oligodendrocytes II Microglia I • Smallest neuroglia • Part of monocyto-macrophage system – Mesodermic origin • Movable and phagocytic • Nuclei elongated – As opposed to other glial cells that have round nuclei • have „spiky“ shape – During activation acquire shape of macrophages Microglia II Microglia III Ependymal cells I (ependymocyti) • Originate from inner (germinal) zone of neuroepithelium • Maintain epiteloid arrangement • ependyme covers CNS cavities – brain ventricles, Sylvius aqueduct, central canal of medulla spinalis • Cells have nexus and zonulae occludentes • Cillia at the apical pole facilitate flow of CSF • tanycytes – Special group o ependymal cells at the bottom of the 3rd ventricle – Have long extensions into nervous tissue – May play role in chemical singal transduction from CSF Ependymal cells II Nerve fibers (neurofibra) • Axons or dendrites covered by special sheaths of ectodermal origin • Nerve fiber bundles form: – In CNS tracts (cover is formed by oligodendrocytes) – In PNS nerves (cover formed by Schwann cells) • We recognize fibers: – Non-myelinated – myelinated Non myelinated nerve fibers I • In the CNS located freely between neurons and glial cells • In the PNS „invaginates“ into simple rifts in Schwann cells • Schwann cells (Schwannocytus) located along nerve fiber mutually interconnected – missing Ranvier fissures Non myelinated nerve fibers II Myelinated nerve fibers I • Myelination occurs in several steps: – Invagination of axon into sulcus of sheat cell (oligodendrocyte or Schwann cell) originate so called mesaxon (mesaxon) – mesaxon „rotates“ around axon by 150x – By modification of cytoplasmic membrane of covering cell originate lipoprotein complex myelin Myelinated nerve fibers II Myelinated nerve fibers III • Between individual Schwann cells is myelin sheath interrupted by Ranvier fissure (nodi interruptionis myelini) • Interval between Ranvier fissures is named internodium and has length 1-2 mm • In the CNS are Ranvier fissures not readily visible • Schmidt-Lanterman incisure (incisurae myelini) – cytoplasm of Schwann cell „imprisoned“ during myelination inside myelin sheath – Form lighter stripes in myelin sheath http://en.wikipedia.org/wiki/Myelin_sheath_gap Myelinated nerve fibers IV Myelin sheath – electrone microscope Schmidt – Lanterman incisures J Neurosci 2013 Nerves I • Formed by bundles of nerve fibers • Nerve fibers have coverings similar to muscle fibers: – endoneurium • Layer of reticular fibers around individual nerve fibers – perineurium • „sleeve“ covering bundles of nerve fibers formed by layers of epitheloid cells • Numerous zonulae occludentes – non passable barrier protecting nerve fibers – epineurium • Tissue cover of whole nerve Nerves II Ganglia I • Nerve ganglia is accumulation of perikarya in the PNS • Have ovoid shape and their surface is covered by pouch from thick non arranged tissue • Typical are so called satellite cells (gliocyti ganglionici) – snall cuboideal cells surrounding neuronal perikarya http://en.wikipedia.org/wiki/Dorsal_root_ganglion http://www.pharmainfo.net/introduction-autonomic-nervous-system/classification Ganglia II • spinal ganglia – sensory (ganglion sensorium) – In posterior radices of spinal nerves and in the course of cranial nerves (V, IX, X) – Contain typical pseudounipolar neurons – Bring in sensory inputs from periphery to CNS • autonomous (vegetative) ganglia (ganglion autonomicum) – – – – In the course of autonomic nerves Contain multipolar neurons Layer of satellite cells is not complete intramural ganglia • parasympatic ganglia in the wall of the hollow organs Ganglia III Development of neural tube I Nervous tissue originates from neuroectoderm • NE originates from ectoderm by induction of notochored neural plate durgin neurulation process creates neural tub = foundation of CNS • Remnant of neuroectoderm separates neural crest (crista neuralis) = foundation of PNS and other structures (ectomesenchyme of the head ) Development of neural tube II • Primary neurulation – Separates ectoderm into three cell types (inside positioned nerve tube, epidermis externally and cells of the neural crest) • Secondary neurulation – Cells of the nerve plate form chorda dorsalis • In the time of 35th somite formation Development of neural tube III Epitelium of nerve tube soon changes into multilayer neuroepithelium where are 3 layers: • inner (germinal) zone (zona ventricularis; matrix germinalis) – Up to half of gravidity richly proliferates (origin of neuroblasts) – Then reduced into ependyme • Middle (shell) zone (zona intermedia; zona pallii) – Formed primarilly by migrating neuroblasts – Gives rise to grey matter • outer (marginal) zone (zona marginalis) – Formed by extensions of neuroblasts Development of neural tube IV Somite (somitus) • somitomeres around 3rd week • At the end of 5th week 42-44 somites http://www.aps.uoguelph.ca/~swatland/HTML10234/LEC5/LEC5.html http://www.uprightape.net/Image_Pages/UA_Fig7-4_SomiteDevel.html Myotome • Central part of initial segment • During differentiation from 4th week it retain longest epitheloid organization • Gives rise to skeletal muscle Sclerotome • Dorsomedial part of initial segment • During differentiation from 4th week transforms into mesenchyme • Thickens around chorda dorsalis • Gives rise to axial skeleton (vertebras, costas, sternum) and basis of the skull Dermatome • Ventrolateral part of initial segment • During differentiation from 4th week transforms into mesenchyme • Migrates into somatopleura • Gives rise to connective tissue basis of skin (dermis and tela subcutanea) • Parts arising from the same dermatome have same innervation via spinal root Composition of brain tissue • Grey matter (substantia grisea) – perikarya of neurons, mostly non myelinated nerve fibers – Protoplasmic astrocytes, oligodendrocytes and microglia • White matter (substantia alba) – Mostly myelinated fibers – Fibrilar astrocytes, oligodendrocytes and microglia http://fuckyeahnervoussystem.tumblr.com/post/1276369326/spinal-cord-light-micrograph-of-a-cross-section http://library.med.utah.edu/WebPath/HISTHTML/NEURANAT/CNS230A.html CNS description - parts • Spinal cord (Medulla spinalis) • Brain stem (Truncus encephali) – – – – Oblongate (Medulla oblongata) Pons (Pons) – formerly pons Varoli Midbrain (Mesencephalon) Hindbrain (Rhombencephalon) • Cerebellum (Cerebellum) • Diencephalon (Diencephalon) • Terminal brain (Telencephalon) – Bazal ganglia (nuclei basales) – Brain cortex (cortex cerebri) – Forebrain (ventral brain) Brain stem Mesencephalon Pons Medulla oblongata Medulla spinalis CNS description • Inside CNS cavities – 4th ventricle, 3rd ventricle and two lateral ventricles • CNS covered by meninx: – Hard meninx (pachymeninx = dura mater) – Soft meninx (leptomeninx) • arachnoidea (arachnoidea mater) • pia (pia mater) http://faculty.irsc.edu/FACULTY/TFischer/AP1/AP%201%20resources.htm • Inside cavities cerebospinal fluid (liquor cerebrospinalis = CSF) http://mortdev.blogspot.cz/2008/09/brain-autopsy.html Brain stem • Transfer of all ascending and descending nerve pathways (tractus) • Reticular formation (RF; formatio reticularis) – Vitaly important reflexory centers • Cardiac activity, respiration, vasomotorics, consciousness • Nuclei of cranial nerves – n. III - XII CNS function • Spine – reflexes, ascending and descending tracts • Brain stem – vitally importatn reflexes (respiratory, cardiovascular, vomitus, eye ball synchro) • Midbrain – hormonal production, circadian rhythm, termoregulation, food intake, autonomic regulation • Terminal brain – Brain cortex: functional cortical areas – Basal ganglias: motion patterns • limbic system – behavior, emotions, memory Peripheral nervous system (Systema nervosum periphericum) • spinal nerves (nervi spinales) – 31 pairs • cranial nerves (nervi craniales) – 12 pairs • autonomic nerves (systema autonomicum) – sympathetic (pars sympathica) – parasympathetic (pars parasympathica) – enteric system Macroscopy of spinal nerve branching Pyramidal tract (Tractus pyramidalis) • 2-neuron pathway • cerebral cortex → skeletal muscle • 1st neuron = pyramidal cell of cortex • 2nd neuron = alfa-motoneuron of anterior horn of spinal cord • decussated (C1 level) • disorder: central contralateral palsy Rami anteriores nervorum spinalium • plexus cervicalis (C1-4) • plexus brachialis (C4-T1) • nn. intercostales (T1-T12) • plexus lumbalis (T12-L4) • plexus sacralis (L4-S4) • plexus coccygeus (S5-Co) Plexus brachialis (C4-T1) • truncus (trunk) superior (C4+C5+C6) medius (C7) inferior (C8+T1) fissura scalenorum • fasciculus (cord) lateralis medialis posterior axilla - relation to a. axillaris • pars supraclavicularis Plexus brachialis - axilla Plexus brachialis Nerves and their roots n. musculocutaneus n. medianus n. ulnaris n. cutaneus antebrachii med. n. cutaneus brachii med. n. axillaris n. radialis C5-7 C5-T1 C8-T1 C5-6 C5-C8 (T1)