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  • NEURONS AND GLIA

  • IntroductionNeurophilosophyBrain (neurons) is the origin of mental abilitiesGlia and NeuronsGlia Insulates, supports, and nourishes neurons90% of brain cells are glial cellsNeuronsProcess informationSense environmental changes Communicate changes to other neuronsCommand body response

  • The Neuron DoctrineThe birth of neurohistologyMicroscopy inventionDiscovery of fixation method for cutting thin slicesStaining methods for selectively coloring parts of cells

    The Nissl StainDeveloped by by the German neurologist Franz NisslStain the nuclei and surrounding material (Nissl body)Made it possible to distinguish neurons vs. glia and to study the arrangements of neurons in different parts of brain (cytoarchitecture)

    Fig2.1

  • The Neuron DoctrineThe Golgi StainCamillo Golgi discovered that by soaking brain tissue in a silver chromate solution, a small percentage of neurons became darkly colored in their entiretySoma (cell body or perikaryon) and neurites (axons and dendrites)

    Fig 2.3

  • The Neuron DoctrineCajals ContributionSantiago Ramon y Cajal used Golgi stain method and worked out the circuitry of many regions of the brain : Father of neuroanatomyGolgi versus CajalReticular theory vs. cell theoryNeuron doctrineNeurons communicate by contact, not continuityFinal proof had to wait until EM got developed in the 1950s

  • The Prototypical NeuronThe Soma~20 um in diameterCytosol: Potassium rich watery fluid inside the cellOrganelles: Membrane-enclosed structures within the somaCytoplasm: Contents within a cell membrane (e.g., organelles, excluding the nucleus)

    Fig2.7

  • The Prototypical NeuronThe AxonBegins with axon hillock, initial tapered segment where action potentials are generated Rough ER does not extend into axon Protein composition of axon membarane is fundamentally different from that of somaNo protein synthesis in the axonMay extend from less than a millimeter to over a meter longMay branch out (generally at right angles) to form axon collaterals that could return to the same cell (recurrent collaterals)Diameter ranges from less than 1 mm to 25 mm in humans - The speed of nerve impulses depends on axonal diameter

  • The Prototypical NeuronThe Axon Terminal (terminal bouton)A site where the axon comes in contact with other neurons and passes information on to themTerminal arbor or boutons en passantSynapse - To fasten togetherInnervation - making synaptic contactDifferences between the cytoplasm of axon terminal and that of axon No microtubules in the terminalPresence of synaptic vesicles (~50 nm in diameter)Dense covering of proteins on the inside surface of the synaptic membraneLarge number of mitochondria (high energy demand)

  • The Prototypical NeuronSynapsePre- and Postsynaptic sides : directionality of information flowSynaptic transmissionSynaptic cleft Electrical-to-chemical-to-electrical transformationNeurotransmitter

  • The Prototypical NeuronAxoplasmic transportWallerian degenerationDegeneration of axon when severed (axotomy) is due to the lack of protein synthesis machinery within axon

    Kandel Fig 55-18 Anterograde transport by kinesin and retrograde transport by MAP-1C (dynein)

  • The Prototypical NeuronSlow Axoplasmic transportPaul Weisss experimentTied off a sciatic nerve (axon) to find that material accumulate on the proximal side of the knotWhen the knot was untied, the bulged out accumulation continued down the axonThe speed of movement was measured to be about 1 - 10 mm per day ; SLOW AXOPLASMIC TRANSPORTOnly anterograde directionSlow transport itself can be at two different speedsSlower (0.2-2.5mm per day) : fibrillar elements of cytoskeleton (neurofilament subunits, tubulins..)Faster (about twice as fast as the slower) : various cytosolic proteins (clathrin, actin, actin-binding proteins, enzymes..)

  • The Prototypical NeuronFast Axoplasmic transportBernice GrafsteinInjected radioactive amino acids into somataTraced the synthesized (hot) proteins along the axon

    Large membraneous organelles are transported via fast transportIncludes vesicles of the constitutive secretory pathways, synaptic vesicles precursor membranes, mitochondria, smooth ER elements..ATP dependent but not protein synthesis dependent (once synthesized)Soma-independent (isolated axon still can transport

  • The Prototypical NeuronDendritesGreek for treeDendritic tree for all the dendrites of a neuronAntennae of neurons - covered with thousands of synapsesDendritic membrane (postsynaptic membrane) contains many specialized receptors for neurotransmittersDendritic spinesSome neurons have these structures for receiving some types of inputsDiscovered by CajalBelieved to isolate various chemical reactionsDynamic structures affected by the type and amount of inputs and developmental changes of environmentFig 2.17Fig 2.18

  • Mental Retardation and dendritic spinesBrain function depends on the highly precise synaptic connections, which are formed during the fetal period and are refined during infancy and early childhood95% of population falls within two standard deviations from the mean of IQ (around 70 when the mean is set to be 100). Some 2-3% of humans with intelligence score below are considered to be mentally retarded IF the cognitive impairment affects the persons ability to adapt their behavior to the setting in which they live

    Fig ACan have many causesGenetic disorders such as PKU or Down syndromeAccidents or infection during pregnancy or early childhoodPoor nutrition during pregnancyEnvironmental impoverishment such as the lack of good nutrition, socialization, sensory stimulation during infancySome with clear physical correlates (retarded growth, abnormal structures of head, hands, and body), most with only behavioral manifestationsDendritic spine abnormality has been found to be correlated with mental retardation

  • Classifying NeuronsClassification Based on the Number of Neurites Unipolar cell Found in invertebrate nervous system - single process with different segments serving as receptive surfaces or releasing terminalsBipolar cell Two neuritesMultipolar cellMost neurons in the brain are multipolarKendal fig 2-4

  • Classifying NeuronsClassification Based on Dendritic and Somatic MorphologiesOften unique to a particular region of the brain Cortex - Stellate cells (star-shaped) and pyramidal cells (pyramid-shaped)Spiny or aspinous

  • Classifying NeuronsFurther ClassificationBased on connections within the CNSPrimary sensory neuronsmotor neuronsinterneuronsBased on axonal lengthGolgi Type I - projection neurons that extend their axons to other parts of the brain (e.g. pyramidal neurons in the cortex)Golgi Type II - local circuit neurons that have short axons that do not extend beyond the vicinity of cell body (e.g. stellate cells in the cortex)Based on neurotransmitter typeCholinergic, glutamatergic, GABAergic

  • GliaSleeping Giants ?Function of Glia Supports neuronal functions Without glia brain cannot function! AstrocytesMost numerous glia in the brainFill spaces between neuronsImporatant regulator of the chemical contents of extracellular spaces (Not much left after filling up)Envelop synaptic junctions - restrict the spreading of released neurotransmittersPossess their own neurotransmitter receptors!!

  • GliaMyelinating GliaOligodendroglia (in CNS) and Schwann cells (in PNS)Insulate axons by wrapping axons around Myelin sheath One Oligodedroglia can provide insulation to several axons but each Schwann cell does to a only a single axonNode of RanvierRegion where the axonal membrane is exposed

  • Glia

    Other Non-Neuronal CellsMicroglia as phagocytes (immune)Ependymal cells provide lining of fluid-filled ventricles and directs cell migration during brain developmentVasculature

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