Cellular Components of the Nervous System

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1 Cellular Components of the Nervous System Lee Anna Cunningham Dept. Neurosciences January 18, 2017 Reading Fundamental Neuroscience, ed. Larry Squire, Chapter 3 Cellular Components of Nervous Tissue

2 CELL TYPES OF THE NERVOUS SYSTEM NEURONS Impulse Conduction Information Processing GLIA Macroglia Oligodendrocytes Schwann Cells Astrocytes Myelination Metabolic Support Blood Brain Barrier Inflammation Information Processing? Microglia Inflammation ENDOTHELIAL CELLS Blood Brain Barrier

3 Number of neurons in the Human Nervous System ~90 billion Number of glial cells in the Human Nervous System- ~360 billion Stars in the Milky Way 100 billion US Federal Deficit in Billion Current US Debt 18.2 Trillion

4 DENDRITIC SPINES

5 NEURONS CLASSIFICATION SCHEMES PROPERTIES EXAMPLES LOCATION FUNCTION CONNECTIONS NEUROTRANSMITTER MORPHOLOGY CNS vs. PNS Motor vs. Sensory Projection vs. Interneuron Cholinergic vs. Adrenergic Multipolar vs. Bipolar

6 Neurons are Polarized Cells with Distinct Structural and Functional Cellular Domains DENDRITES SOMA AXON Camillo Golgi

7 Basic Morphological Features of Neurons

8 Asymetric Synapse (excitatory) Symmetric Synapse (Inhibitory)

9 Site of Excitatory Synapses Display Morphological Plasticity DENDRITIC SPINES Structure - Stability - Function Site of Postsynaptic Density - Intricate interaction of glutamate receptors, scaffold proteins and actin cytoskeleton

10 Protein Synthesis Occurs Primarily in the Cell Body and Dendrites Nissl Golgi Axon is largely devoid of protein synthetic machinery Microtubules Neurofilaments Smooth ER

11 Microtubules Largest (25 nm) Axonal Transport of Organelles Intermediate Filaments (10 nm) Neurofilaments Unique to neurons Structure and Stability NEURONAL CYTOSKELETAL FILAMENTS Microfilament Actins (7 nm) Shape and ECM /cell surface signaling and Growth Cone Function, pre and post synaptic specializations Neurofilaments NEUROFILAMENTS MICROTUBULES

12 MICROTUBULES ARE THE TRACTS FOR AXONAL TRANSPORT Proteins and Organelles are Transported Along the Axon in both Anterograde (away from cell body) and Retrograde (toward cell body) Directions by FAST AXONAL TRANSPORT ( mm/day) Basis of neuroanatomical tracing

13 NEUROANATOMICAL TRACING (Identification of Neuronal Pathways) Relies on Axonal Transport Retrograde Tracer Into Target Region (HRP, Fluorogold)

14 Cytoskeletal Associated Proteins are Compartmentalized and Can be used to Distinguish Somatodendritic from Axonal Regions using Immunocytochemical Staining Somatodendritic Compartment Axon TAU microtubule MAP-2 MAP2 TAU

15 Glial Cells

16 Oligodendrocytes are the myelinating cells of the CNS

17

18 Myelin is a specialized cytoplasmic extension of the oligodendrocyte.

19 MYELIN STRUCTURE Interperiod line Major Dense Line Extracellular Cytoplasm CNS MBP PNS Lipid Bilayer MAG PLP Po

20 OLIGODENDROCYE MYELINATING CELLS OF THE CNS Internodal Segment Nodes of Ranvier Myelination increases the axonal conduction velocity by allowing current to jump from node to node by saltatory conduction. This minimizes the need for giant axons and conserves space. An evolutionary advantage. Not all axons are myelinated.

21 CNS PNS Oligodendrocyte Schwann Cell Neuroepithelium Neural Crest 1 Oligo : multiple segments 1 Schwann : 1 Segment

22 ASTROCYTES (STAR) Support Cells CNS Glial Fibrillary Acidic Protein (GFAP)+ Neuroepithelial Derivatives FIBROUS White Matter Multifunctional 1. Developent - Neuroblast migration, Synaptogenesis, BBB induction, Neurotrophic Support, Stem cells 2. Adult - K+ homeostasis, BBB maintenance, CNS Metabolism and Blood Flow, Neuronal synaptic transmission 3. Disease - Neuroinflammation, Glial Scar Formation PROTOPLASMIC Grey Matter

23 DEVELOPMENT Radial Processes of Glial Cells Serve as Tracts for Migrating Neuroblasts during early CNS development.

24 DEVELOPMENT Astrocytes promote the formation of new synapses are likely to be involved in early synaptogenesis

25 CEREBRAL VASCULATURE Astrocyte endfeet induce and maintain blood brain barrier properties of endothelial cells of intraparenchymal cerebral capillaries

26 ASTROCYTES AND BRAIN ENERGY METABOLISM Glutamate-Activated Glycolosis

27 NEUROTRANSMITTER UPTAKE AND METABOLISM Astrocytes remove glutamate and GABA from the synaptic cleft through high affinity transporters. The neurotransmitters are recycled by conversion to Glutamine by the astrocyte enzyme, glutamine synthesase (GS). Glutamine is returned to neurons to serve as the precursor to GABA and Glutamate. Disruption of astrocyte glutamate transporter function results in excitotoxic death of neurons.

28 NEURONAL TRANSMISSION Perisynaptic astrocytes might regulate neuronal synaptic neurotransmission through the release of gliotransmitters. Glia release glutamate which can stimulate pre and post-synaptic receptors on neurons. This involves bidirectional communication between neurons and astrocytes.

29 D8Xoii503k0

30 NEUROINFLAMMATION GLIAL SCAR FORMATION CNS INJURY Normal Astrocyte Reactive Astrocyte IL1b TNF PROLIFERATION, PROCESS FORMATION, INCREASED GFAP EXPRESSION, CYTOKINE RELEASE, ECM PRODUCTION BREAKDOWN OF BBB and IMMUNE CELL INFILTRATION GLIAL SCAR FORMATION and INHIBITION OF AXON REGENERATION

31 Principle Immune Effector Cells in CNS Related to Blood Monocytes and Tissue Macrophages Subclasses: Leptomeningeal Perivascular Parenchymal Derived from Bone Marrow Seed CNS in early development Resident macrophages MICROGLIA

32 MICROGLIAL ACTIVATION Injury or Pathogens Resting Activated Phagocytic CD11b+ Ox42+ ramified bushy round ED1+,MAC-1 MHC II expression Amplify inflammation Cytokine Release Immune Cell Recruitment to injury site Release of Neurotoxic Substances Nitric Oxide and TNF

33 MICROGLIA AS MEDIATORS OF INFLAMMATORY AND DEGENERATIVE DISEASES HIV Infection of CNS, Alzheimer s Disease Plaque Formation, Multiple Sclerosis, Parkinson s disease

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