Nerve tissue Brno, April 2024 • Nerve tissue • Neuron • Synapse • Neuroglia • Nerve • Saltatory signal propagation • Development of nerve tissue • Nerve regeneration Nerve tissue – general 1 Controls and integrates all body activities within limits that maintain life Key functions • sensing changes with sensory receptors • interpreting and remembering those changes • reacting to those changes with effectors 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 Anatomical organization of nervous system 2 Nerve tissue – General – Neuron 1 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) Neuron 3 - PerikaryonPosition: 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 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 10 lipofuscine granules Cilium derived from unused centriole Neuron 7 – Neurites / Processes 11 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 15 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 16 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) 18 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 21 Synapse 4 22 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 One neuron may have 1 000 to 10 000 synapses !!! 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 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: ✓ form a supportive framework of nervous tissue ✓ have extensions (perivascular feet) that contact blood capillaries that stimulate them to form a tight seal called the blood-brain barrier ✓ convert blood glucose to lactate and supply this to the neurons for nourishment ✓ nerve growth factors secreted by astrocytes promote neuron growth and synapse formation ✓ communicate electrically with neurons and may influence synaptic signaling ✓ regulate chemical composition of tissue fluid by absorbing excess neurotransmitters and ions ✓ astrocytosis or sclerosis – when neuron is damaged, astrocytes form hardened scar tissue and fill space formerly occupied by the neuron ✓ contains GFAP Neuroglia - Astrocytes protoplasmic astrocyte fibrous astrocyte capillary perivascular foot (predominant in grey matter) (predominant in white matter) Neuroglia - Oligodendrocytes ✓ smaller than astrocytes; darker, round nucleus, abundant RER, well developed golgi apparatus ✓ form myelin sheaths in CNS ✓ one cell serves more then one axon ✓ cannot migrate around axons (unlike Schwann cells) must push newer layers of myelin under the older ones so myelination spirals inward toward nerve fiber ✓ nerve fibers in CNS have no Schwann sheath (neurilemma) or endoneurium ✓ each arm-like process wraps around a nerve fiber forming an insulating layer that speeds up signal conduction ✓ damaged in multiple sclerosis oligodendrocyte Neuroglia - Microglia ✓ smallest neuroglial cell ✓ small, dark, elongated nuclei ✓ possess phagocytotic properties ✓ when activated – antigen presenting cell ✓ originate in bone marrow (mesodermal origin) Neuroglia – Ependymal cells ✓ line ventricles of CNS and central canal of spinal cord ✓ cuboidal or low columnar shape ✓ no basal lamina ✓ secrete cerebrospinal fluid (CSF) ✓ some are ciliated, facilitate movement of CSF ✓ participate in formation of Choroid plexus 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 only by 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 double contoured nerve fiber (myelinated) gray nerve fiber (non-myelinated) Neuroglia in PNS – Schwann cells 3 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 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 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” 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