NerveNerve tissuetissue 1. Nerve tissue – characteristic s, histogenesis and classification 2. – classes and structure :  cell body (perikaryon)  neuronal processes 3. Nerve fibers – types 4. 5. Neurotransmitters and receptors 6. Neuroglial cells 7. Nerve endings :  sensory (afferent ) receptors  effector (efferent) endings NerveNerve tissuetissue  TextusTextus nervosus:nervosus:  cellscells – nervenerve andand glialglial cellscells  extracellularextracellular matrixmatrix  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 by the plasma membrane

Prof. Dr. Nikolai Lazarov 2 Classification of

Prof. Dr. Nikolai Lazarov 3 NeurulationNeurulation  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  ridge  PNS  transverse segmentation of neural tube:  cranial neuropore – Е25  caudal neuropore – Е27 Prof. Dr. Nikolai Lazarov 4 HistogenesisHistogenesis  undifferentiated neuroepithelial cells (stem cells) – pluripotential:  unipotent progenitor cells :  neuroblasts (immature neurons)  unipolar, bipolar and multipolar  glioblasts (glial precursor cells)   protoplasmic  fibrillar astrocytes  ependymal cells   mesenchymal origin?  histogenesis – zones :  ependymal layer  mantle layer  marginal layer

Prof. Dr. Nikolai Lazarov 5 NerveNerve cellscells  neuron – more than 10 billion in the human NS  cell body (perikaryon)(perikaryon  – Golgi type І and ІІ neurons 

Prof. Dr. Nikolai Lazarov 6 CellCell bodybody  perikaryon (Gr. peri,peri around + karyon, nucleus)  a trophic and receptive center of the neuron  diameter – 2040 m (4120 m)  composition:  shape – pyramidal, stellate, fusiform, flaskshaped etc.  large, euchromatic nucleus with a prominent nucleolus  organelles:  Nissl bodies  Golgi complex  mitochondria  microtubules   lypofuscin and neuromelanin

Prof. Dr. Nikolai Lazarov 7 NerveNerve processesprocesses  axon (Lat. axis, axle or pivot)  length – 1 mm100 cm diameter – 0.220 m  structure:    initial segment  collateral branches  axonal ending ( terminal)    :axoplasm  ribosomes – occasionally absence of rER and GA  axonal transport:transport  slow stream – 0.2 m/day anterograde flow  fast stream – 1040 cm/day anterograde and retrograde flow

Prof. Dr. Nikolai Lazarov 8 NerveNerve processesprocesses  dendrites (Gr. dendron, tree)  number – variable, most frequently 515 8090% of the surface  structure:   short, dendritic tree  spines  dendritic cytoplasm:cytoplasm  Nissl bodies  mitochondria  neurofilaments  microtubules  absence of Golgi complex

Prof. Dr. Nikolai Lazarov 9 BasicBasic neuronalneuronal typestypes  functional classes:  morphological classes:  motor (efferent ) neurons  pseudounipolar neurons  sensory (afferent ) neurons  bipolar neurons   multipolar neurons

Prof. Dr. Nikolai Lazarov 10 NerveNerve fibersfibers  Nerve fiber :  axon  sheath derived from cells of ectodermal origin:  – CNS  Types of nerve fibers:fibers  – PNS  unmyelinated – 0.12 m diameter  both in the CNS and PNS  absence of nodes of Ranvier  0.52 m/sec conduction velocity  myelinated – 120 m  both in the CNS and PNS  mesaxon  nodes of Ranvier  internodal segment – 12 mm  Schmidt -Lanterman clefts  4120 m/sec velocity

Prof. Dr. Nikolai Lazarov 11 MyelinationMyelination  myelination in humans :  begin – fetal period  end – 7 years  regulation – neuroregulin NRG1  forming cells:  oligodendrocytes – CNS  Schwann cells – PNS  myelin :  lipids – 70%  proteins – 30% in CNS  MBP (myelin basic protein)  P0 – peripheral  PMP22 – peripheral axons  myelin sheath:  major dense lines  intraperiod lines

Prof. Dr. Nikolai Lazarov 12 SynapsesSynapses  synapse (Gr. synaptein , to join together )  structure:  presynaptic component ,  presynaptic membrane  presynaptic grid  mitochondria  synaptic vesicles – (2065 nm)  transmitters C.S. Sherrington  synaptic cleft (2030 nm) 1857 –1952  postsynaptic membrane  postsynaptic thickening  receptors

Prof. Dr. Nikolai Lazarov 13 TypesTypes ofof synapsessynapses  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 NeurotransmittersNeurotransmitters

 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 TransportersTransporters andand receptorsreceptors  Transporters:Transporters  Acetylcholinesterase (AChE)  integral proteins – Na + transport symporters  Transmitter receptors:receptors  ionotropic – transmitter gated ion channels  for ACh, GABA, Gly, SER  for glutamate • NMDAreceptors • nonNMDAreceptors (AMPA and kainate)  metabotropic receptors  Gprotein coupled receptors • muscarinic ACh receptors • α and βadrenergic receptors • receptors for Glu, SER, GABA, neuropeptides  tyrosine kinases receptor family  guanylate cycl ase receptor s  cytokine receptors  autoreceptors

Prof. Dr. Nikolai Lazarov 16 Arvid CarlssonCarlsson, Paul Greengard andandand Eric Kandel for their discoveries concerning "signal transduction in the nervous system" Arvid CarlssonCarlsson, 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 GreengardGreengard, 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 KandelKandel, 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 NeurogliaNeuroglia

 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 CentralCentral gliocytesgliocytes (Gr . astron  astrocytes – star )  protoplasmic  fibrous astrocytes  oligodendrocytes (Gr. oligos  large light – small )  mediumsized  small dark – ¼ of the light cells  myelinforming 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 )  (ependymal astrocytes)  microglia – 15% of the total cells of CNS  nondividing cells  derived from monocytes  role of macrophages (mononuclear phagocyte system in ) Prof. Dr. Nikolai Lazarov 19 PeripheralPeripheral gliocytesgliocytes  Schwann cells (neurolemmocytes )

 neural crest origin  myelinforming 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 C.S. Sherrington  by sensory modality: 1857 –1952  baroreceptors – respond to pressure  chemoreceptors – chemical stimuli  mechanoreceptors – mechanical stress  – 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 SenseSense ofof touchtouch  four kinds of touch sensations :  light t ouch (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 EncapsulatedEncapsulated receptorsreceptors

 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 EffectorEffector nervenerve endingsendings  myoneuralmyoneural junctionjunction – 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 ThankThank youyou ……

Prof. Dr. Nikolai Lazarov 25