Neurobiology Cells of the nervous system Anthony Heape 2011 1 Cells of the nervous system Neuroglia : part 2 The non excitable cells of the nervous system that provide support to neuronal survival and function 2 1
Myelinating Neuroglia CNS Oligodendrocytes Form multiple myelin sheaths around one or more axons Radial glia Astrocytes Regulate extracellular brain fluid composition Promote tight junctions to form blood-brain barrier Ependymal Cells Line brain ventricles and spinal cord central canal Help form choroid plexuses that secrete CSF Microglia Specialized macrophages PNS Schwann cells Wrap around one portion of only one axon to form a single myelin sheath Satellite cells Surround neuron cell bodies in ganglia, provide support and nutrients CNS PNS 3 CNS Myelin, or PNS Myelin? What s the difference? They (almost) look the same and do the same job. So who cares? 4 2
Oligodendrocytes & Schwann Cells Embryological Origin 5 From neural plate to neural tube Notoch ordal plate Neural crest Neural crest Neural tube 6 3
Cellular structure of the neural tube 7 Basal progenitor (BP) Early stage neuron Late stage neuron from BP Late stage neuron from RG Radial glia (RG) (Apical surface) Neuroepithelium to oligodendroglia transition Neuroepithelial cells (NEP) progressively convert to radial glia. Radial glia elongate following the thickening of the neural tube wall. Radial glia produce neurons and astrocytes in first waves. Oligodendrocytes appear in third wave of radial glial cell proliferation and differentiation. 8 4
Fates of cells from the neural crest 9 From neural crest to Schwann cell precursors PNS neurons Ganglion = a cluster of a large number of neuronal cell bodies outside of the brain 10 5
Oligodendrocytes Location and Structure 11 White & Grey Matter in the CNS Grey matter is rich in neuronal cell bodies White matter is rich in myelinated neuronal processes Grey matter Spinal cord White matter Grey matter Brain White matter Optic nerve 12 6
White matter in the brain 13 The optic nerve The olfactory nerves (CN I) and the optic nerves (CN II) do not originate from the brainstem. Of all the cranial nerves, only the optic nerves are myelinated by oligodendrocytes. Optic nerve 14 7
CNS Myelin White matter in the cerebrum The CNS myelin sheath is a segmental, fatty insulation composed of modified oligodendrocyte plasma membrane that surrounds axons and promotes the rapid and efficient conduction of electrical impulses along the axons. Oligodendrocyte soma (associated with several myelinated axons) Myelin Optic nerve Transverse section Myelinated Axons Axon 15 The myelin sheath is segmented Each CNS myelin unit is derived from a single oligodendrocyte A given oligodendrocyte may form myelin units around several axons. Each axon may have several myelin units derived from the same oligodendrocyte Several oligodendrocytes usually contribute to myelin units around a given axon The oligodendrocyte soma is located at a distance from its myelin units, and is linked to them via cellular processes. Node of Ranvier OG-GalCB Myelin unit Myelin sheath astrocyte Oligodendrocyte 16 8
Oligodendrocytes & CNS myelin Mature myelin in the CNS The compact myelin compartment is a tightly packed, multi-lamellar, membrane structure. Cytosol is excluded by the fusion of the inner leaflets of the oligodendrocyte (O) plasma membrane lipid bilayer. Non compact myelin compartments in CNS myelin include: Paranodal loops (PL) of the nodes of Ranvier (NR) Periaxonal collar (PC) & mesaxons O O Optic nerve O O CM CM Astrocyte foot process NR PL axon PC axon CM 17 Intra sheath communication and adhesion in the CNS 18 9
Schwann cells Location and Structure 19 Location of Schwann cells Olfactory ensheathing cells Oligodendrocytes? Schwann cells 20 10
Location of Schwann cells 21 Location of Schwann cells Schwann cells form the last layer surrounding the axons of peripheral nerves 22 11
Location of Schwann cells 100x epineurium endoneurium myelin sheath fascicle fascicle axon perineurium Peripheral Nerve (cross section) 23 Location of Schwann cells 14-day-old mouse sciatic nerve PNS nerves, like the CNS white matter, get their colour from myelin Images from Pereira et al: JCB (2009) 185:147-161 24 12
Schwann cells Theodore Schwann (19th cent. German anatomist) Form the myelin sheaths around the larger nerve fibers and amyelin sheaths around non myelinated (ANS) nerve fibres in the PNS. They also have trophic functions (e.g. secrete NGF) and contribute to neuronal regeneration The soma of the Schwann cell is always in direct contact with its myelin sheath. 25 Schwann cells Mature myelin in the PNS CM SL CM Compact myelin (CM) Schmidt Lantermann (SL) clefts (PNS) Paranodal loops (PL) of the nodes of Ranvier Periaxonal collar (PC) CM ax PL PC CM CM ax ax ax 26 13
Schwann cells Gap junctions The nodes of Ranvier are covered by interdigitations of the plasmalemma of adjacent Schwann cells 27 Schwann cell sheaths in the PNS All mature Schwann cell sheaths are enclosed in a basal lamina secreted by the Schwann cells. CM ax Axonal segregation Fetal fibres promyelin fibre Sciatic nerve (spinal nerve) Basal lamina C fibres (ANS) Vagus nerve (cranial nerve X) 28 14
Differences between CNS and PNS myelins CNS PNS Myelin Yes Yes Myelin-producing cell Oligodendrocyte Schwann cell Embryological origin Neural tube Neural crest Associated cell-types Astrocytes (at nodes of Ranvier) None Basal lamina and collagenbased connective tissue No Yes Number of sheaths/cell 30-40 1 Intra-sheath junctions & channels Myelin-specific proteins Both have Radial component (tight junctions) MAG, MBP, PLP/DM20, MOG Low H 2 O content Schmidt-Lanterman incisures (+ gap junctions) MAG, MBP, P0, PMP22 High lipid content (responsible for white colour of myelinated PNS nerves and CNS white matter ) 29 30 15
31 MYELINATION myelin: a highly differentiated plasma membrane of Oligodendrocytes (CNS) and Schwann Cells (PNS) The Four Stages of Myelination Contact Radial sorting & Envelopment Mesaxon extension Compaction & Growth (Transverse sections) 32 16
Myelin function in the CNS and PNS The myelin sheath is segmental, presenting discontinuities at (±) regular intervals (forming the nodes of Ranvier). Note: the axon is NOT naked at the nodes. Voltage gated Na + and K + channels are clustered at the nodes. The lipid rich, water poor, nature of compact myelin gives the latter good electrical insulating properties. Action potentials are transmitted much faster along the axons (by saltatory conduction) due to the ion channel clustering and the insulating properties of the myelin sheath. 1 mm (1000 nsec) 33 Myelin and action potential transmission speed The speed with which the action potentials are propagated along the axons depends on: The diameter of the axon (determines the number and surface density of voltage gated ion channels) The presence, or absence of a myelin sheath around the axon (saltatory conduction is faster) The thickness of the myelin sheath (thicker is faster). Nerve fibres (axons) of the PNS have been placed into 3 categories based on these criteria A fibres B fibres C fibres Note: belong to neurons of the somatic nervous system. They are generally medium to large diameter axons with myelin sheaths of variable thickness. A fibres are further sub divided into alpha (fastest: 100 m/sec), beta, delta and gamma (slowest: 20 m/sec) fibres. belong to neurons of the ANS. They are medium diameter axons with thin myelin sheaths, and an action potential transmission speed of 3 15 m/sec. also known as Remak fibres, belong to neurons of the ANS. They are small diameter axons with amyelin sheaths (i.e. no myelin), and an action potential transmission speed of 0.7 2.3 m/sec. different fibre types (A, B, or C) predominate in different peripheral nerves, but all three may be present: e.g. B fibres predominate in the vagus nerve, while A fibres predominate in the sciatic nerve. 34 17
Myelinating Neuroglia 35 18