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Nerve tissue 1. Nerve tissue – characteristics, histogenesis and classification 2. Neurons – classes and structure: cell body (perikaryon) neuronal processes 3. Nerve fibers – types 4. Synapses 5. Neurotransmitters and receptors 6. Neuroglial cells 7. Nerve endings: sensory (afferent) receptors effector (efferent) endings Nerve tissue Textus nervosus: cells – nerve and glial cells extracellular matrix main functions: sensing stimuli and creating, analyzing and integrating information regulates and controls body functions provides the unity with the environment properties: irritability capacity to respond to a stimulus – generation of a nerve impulse conductivity capacity to transfer the response throughout the neuron by the plasma membrane Prof. Dr. Nikolai Lazarov 2 Classification of nervous system Prof. Dr. Nikolai Lazarov 3 Neurulation embryonic origin: neuroectoderm formation of neural tube (neurulation) neurulation begin of the process – E17 neural (primary embryonic) induction – signaling molecules (growth factors) from the underlying notochord: neural plate neural groove neural fold neural tube CNS neural crest ganglion ridge PNS transverse segmentation of neural tube: cranial neuropore – Е25 caudal neuropore – Е27 Prof. Dr. Nikolai Lazarov 4 Histogenesis undifferentiated neuroepithelial cells (stem cells) – pluripotential: unipotent progenitor cells: neuroblasts (immature neurons) unipolar, bipolar and multipolar glioblasts (glial precursor cells) oligodendrocytes protoplasmic astrocytes fibrillar astrocytes ependymal cells microglia mesenchymal origin? histogenesis – zones: ependymal layer mantle layer marginal layer Prof. Dr. Nikolai Lazarov 5 Nerve cells neuron – more than 10 billion in the human NS cell body (perikaryon) (perikaryon axon – Golgi type І and ІІ neurons dendrites Prof. Dr. Nikolai Lazarov 6 Cell body perikaryon (Gr. peri, peri around + karyon, nucleus) a trophic and receptive center of the neuron diameter – 20-40 µm (4-120 µm) composition: shape – pyramidal, stellate, fusiform, flask-shaped etc. large, euchromatic nucleus with a prominent nucleolus organelles: Nissl bodies Golgi complex mitochondria microtubules neurofilaments lypofuscin and neuromelanin Prof. Dr. Nikolai Lazarov 7 Nerve processes axon (Lat. axis, axle or pivot) structure: length – 1 mm-100 cm diameter – 0.2-20 µm axon hillock initial segment collateral branches axonal ending (terminal) synapse axolemma axoplasm: axoplasm ribosomes – occasionally absence of rER and GA axonal transport: transport slow stream – 0.2 µm/day anterograde flow fast stream – 10-40 cm/day anterograde and retrograde flow Prof. Dr. Nikolai Lazarov 8 Nerve processes dendrites (Gr. dendron, tree) number – variable, most frequently 5-15 structure: 80-90% of the surface short, dendritic tree dendrite spines dendritic cytoplasm: cytoplasm Nissl bodies mitochondria neurofilaments microtubules absence of Golgi complex Prof. Dr. Nikolai Lazarov 9 Basic neuronal types morphological classes: pseudounipolar neurons bipolar neurons multipolar neurons Prof. Dr. Nikolai Lazarov functional classes: motor (efferent) neurons sensory (afferent) neurons interneurons 10 Nerve fibers Types of nerve fibers: fibers Nerve fiber: axon sheath derived from cells of ectodermal origin: oligodendrocyte – CNS Schwann cell – PNS unmyelinated – 0.1-2 µm diameter both in the CNS and PNS absence of nodes of Ranvier 0.5-2 m/sec conduction velocity myelinated – 1-20 µm both in the CNS and PNS mesaxon nodes of Ranvier internodal segment – 1-2 mm SchmidtSchmidt-Lanterman clefts 4-120 m/sec velocity Prof. Dr. Nikolai Lazarov 11 Myelination myelination in humans: begin – fetal period end – 7 years regulation – neuroregulin NRG1 Myelin-forming cells: oligodendrocytes – CNS Schwann cells – PNS myelin: lipids – 70% proteins – 30% in CNS MBP (myelin basic protein) P0 – peripheral axons PMP-22 – peripheral axons Prof. Dr. Nikolai Lazarov myelin sheath: major dense lines intraperiod lines 12 Synapses synapse (Gr. synaptein, to join together) structure: presynaptic component, axon terminal presynaptic membrane presynaptic grid mitochondria synaptic vesicles – (20-65 nm) transmitters C.S. Sherrington synaptic cleft (20-30 nm) postsynaptic membrane 1857–1952 postsynaptic thickening receptors Prof. Dr. Nikolai Lazarov 13 Types of synapses way of transmission: electrical synapses chemical synapses contacting structures: axosomatic synapses axodendritic axoaxonic dendrodendritic somatodendritic etc. morphologically: asymmetrical (type I) – Glu symmetrical (type IІ) – GABA functionally: excitatory synapses inhibitory synapses atypical synapses: reciprocal dendrodendritic serial synapses “ribbon” synapse synaptic glomeruli Prof. Dr. Nikolai Lazarov 14 Neurotransmitters neurotransmitters – criteria neuromodulators types of neurotransmitters: classical transmitters amino acids biogenic amines other major transmitters – ACh neuroactive peptides (neuropeptides) atypical neural messengers: arachidonic acid derivatives purines adenosine, ATP gaseous – NO, CO postsynaptic effect: excitatory acetylcholine glutamate aspartate inhibitory monoamines GABA and glycine Prof. Dr. Nikolai Lazarov 15 Transporters and receptors Transporters: Transporters Acetylcholinesterase (AChE) integral proteins – Na+ transport symporters Transmitter receptors: receptors ionotropic – transmitter-gated ion channels for ACh, GABA, Gly, SER for glutamate • NMDA-receptors • non-NMDA-receptors (AMPA and kainate) metabotropic receptors G-protein-coupled receptors • muscarinic ACh receptors • α- and β-adrenergic receptors • receptors for Glu, SER, GABA, neuropeptides tyrosine kinases receptor family guanylate cyclase receptors cytokine receptors autoreceptors Prof. Dr. Nikolai Lazarov 16 Arvid Carlsson, Carlsson Paul Greengard and Eric Kandel for their discoveries concerning "signal transduction in the nervous system" Arvid Carlsson, Carlsson Department of Pharmacology, Göteborg University, Sweden, is rewarded for his discovery that dopamine is a brain transmitter of great importance for our ability to control movements that has led to the realization that Parkinson's disease is caused by a lack of dopamine in certain parts of the brain. Paul Greengard, Greengard Laboratory of Molecular and Cellular Science, Rockefeller University, New York, USA, is rewarded for his discovery of how dopamine and a number of other transmitters exert their action in the nervous system. Eric Kandel, Kandel Center for Neurobiology and Behavior, Columbia University, New York, USA, is rewarded for his discoveries of how the efficiency of synapses can be modified, and which molecular mechanisms that take part. Prof. Dr. Nikolai Lazarov 17 Neuroglia Glial cells – glioblastic origin: central – macroglia and microglia (in CNS) peripheral – in PNS central gliocytes – neural tube: astrocytes oligodendrocytes ependymal cells microglial cells peripheral gliocytes – neural crest: Schwann cells (neurolemmocytes) satellite cells of Cajal (syn: mantle cells or amphicytes) Prof. Dr. Nikolai Lazarov 18 Central gliocytes astrocytes (Gr. astron – star) protoplasmic fibrous astrocytes oligodendrocytes (Gr. oligos – small) large light medium-sized small dark – ¼ of the light cells myelin-forming cells in the CNS ependymal cells – neural crest line the ventricles of the brain and central canal of the spinal cord absorption and secretion of cerebrospinal fluid (liquor) tanycytes (ependymal astrocytes) microglia – 15% of the total cells of CNS non-dividing cells derived from monocytes role of macrophages (mononuclear phagocyte system in nervous tissue) Prof. Dr. Nikolai Lazarov 19 Peripheral gliocytes Schwann cells (neurolemmocytes) neural crest origin myelin-forming cells in the PNS maintenance of the axon integrity phagocytotic activity and cellular debris that allows for regrowth of PNS neuron satellite cells (amphicytes) in sensory and autonomic ganglia help regulate the external chemical environment Prof. Dr. Nikolai Lazarov 20 Sensory receptors – classification 3 main groups – Sherrington, 1906: exteroceptors proprioceptors interoceptors by sensory modality: C.S. Sherrington 1857– 1857–1952 baroreceptors – respond to pressure chemoreceptors – chemical stimuli mechanoreceptors – mechanical stress nociceptors – pain perception thermoreceptors – temperature (heat, cold or both) by location: cutaneous receptors – in the skin muscle spindles – in the muscles by morphology: morphology free nerve endings encapsulated receptors Prof. Dr. Nikolai Lazarov 21 Sense of touch four kinds of touch sensations: light touch (contact) cold heat pain free nerve endings: endings unencapsulated unspecialized, detect pain most widely distributed, most numerous in the skin, mucous&serous membranes, muscle, deep fascia, viscera walls peritrichal endings of hair follicles tactile discs of Merkel: Merkel mechanoreceptors – pressure and texture superficial layers of glabrous and hairy skin Prof. Dr. Nikolai Lazarov 22 Encapsulated receptors tactile corpuscles of Meissner – glabrous skin end bulbs (of Krause) – responds to pressure, genital corpuscles Pacinian (Vater-Pacini) corpuscles – vibration Golgi-Mazzoni corpuscles – in the fingertips Ruffini endings – responds to pressure neurotendinous organs (Golgi tendon organs) neuromuscular spindles – proprioceptors: intrafusal fibers extrafusal fibers Prof. Dr. Nikolai Lazarov 23 Effector nerve endings myoneural junction – motor end plate: structure: myelinated axon collaterals ~50 axon terminals (boutons) • synaptic vesicles – ACh • presynaptic membrane sarcolemma junctional folds postsynaptic membrane • nicotinic ACh receptors autonomic effector endings: sympathetic – adrenergic (NA) parasympathetic – cholinergic (ACh) purinergic – ATP and adenosine do not make specialized synaptic contacts Prof. Dr. Nikolai Lazarov 24 Thank you… Prof. Dr. Nikolai Lazarov 25