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Neurobiology

Neurobiology. Outline. Basic plan of the nervous system Cellular neurobiology and – physiology Neurotransmission Neuroplasticity N euromodulation Stem cells in neurology Circadian rhythm , sleep , wakefulness Windows on the brain

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Neurobiology

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  1. Neurobiology

  2. Outline • Basic plan of the nervous system • Cellular neurobiologyand –physiology • Neurotransmission • Neuroplasticity • Neuromodulation • Stem cells in neurology • Circadianrhythm, sleep, wakefulness • Windows on the brain • Pathophysiology of epilepsyandepileptogenesis • Visual perception, attention andspatialcognition • The prefrontal cortex and executive brainfunctions

  3. Chapter 1:Basic plan of the nervous system

  4. Evolution

  5. Evolution

  6. Evolution • excitatory/inhibitroy switches • pattern detectors/generators • pacemakers

  7. Evolution

  8. Development of vertebrate NS

  9. Development of vertebrate NS

  10. Development of vertebratebrain

  11. Basic plan of system connectivity

  12. Adult mammaliannervous system

  13. Chapter 2:Cellular Neurophysiology

  14. Cellular components of nervous tissue • Neurons • Inhibitory neurons • localconnections • distantconnections • Excitatory neurons • localconnections • distantconnections • Neuromodulatory neurons

  15. Inhibitorylocal circuit neurons • Inhibitoryinterneurons of cerebral cortex • Contain the inhibitory neurotransmitter GABA • Localinhibitoryeffects • Richvariety of targets andmorphoogies • Basket cells: inhibitionto soma • parvalbuminpositive, cholecystokinin • Chandeliercells • axonalboutons • axon initial segment • axoaxoniccells • most powerfull • Double bouquet cells • Martinotticells • Neurogliaformcells

  16. Inhibitoryprojection neurons • Medium-sizedSpinycells (only in striatum) • Denselycoveredwithspines • Major output of striatum • GABA, neuropeptidesandcalbindin • Dramaticloss in Huntington diease • invountarymovementsand dementia • Purkinjecells • Cerebellar cortex • GABA andcalbindin • Spinocerebellarataxia (ataxicgait, dysarthria, tremor)

  17. ExcitatoryLocal Circuit Neurons • Spinystellatecells • loollikepyramidal neurons • lackapicaldendrite • restrictedcorticallocation • Rela y of thalamicinputs

  18. Excitatoryprojection neurons • Pyramidalcells • highlypolarized • orthogonaltocorticalsurface • large dendriticarborization • axonswithcollateral branches • subdivisionsbased on morphology, laminarlocation, connectivity

  19. Excitatoryprojection neurons • Spinal motor neurons • α-motor neurons • skeletalmuscles/spindleorgans • ventral root of peripheralnerves • somatotopicrepresentation • acetylcholine

  20. Neuromodulatory neurons • Dopaminergic neurons • pars compacta substantia nigra • ventraltegmental area • projectsto large expanses of cerebral cortex andbasalganglia • Serotonergic neurons • Raphe nuclei • Noradrenergic neurons • Locus coeruleus

  21. Neuroglia • Oligodendrocytes, microglia, astrocytes • Schwanncells

  22. Oligodendrocytes • Myelination • axonalsize <<<< insulation • Squid axon (10-20 m/s)

  23. Schwanncells • Schwanncells (diffwitholigodendrocytes) • individualmyelinatingschwanncells form a single internode • ECM secretion • Respondvigorouslytoinjury • growth factor secretion • debrisremoval • axonalguidancefunction of basal lamina • P0 (PNS) / PLP (proteolipidprotein; CNS) • heavy packingpossiible

  24. Astrocytes • CNS homeostasis • Protoplasmatic • Fibrousastrocytes • Radialglia • Syncitium (gap junctions) • GFAP, S-100

  25. Astrocytes • Multiple roles • Support function • Brain homeostasis • Blood brainbarrier • Angiogenesis • Neurogenesis andguidance • Growth factors • Recycling/buffering of neurotransmitters andions • Hypertrophic/hyperplastic: astrogliosis

  26. Astrocytes

  27. Astrocytes

  28. Microglia • Bonemarrowderived: monocytes • Phagocytosis • Growth factors and cytokines • angiogenesis • gliogenesis • Antigen presentation • Homeostasis

  29. Vasculature

  30. Vasculature • Endothelialtightjunctions • Blood brainbarrier (BBB) • Regulated transfer • P-gp/MDR (drugs) • GLUT-1 (glucose) • L-DOPA • Disruption • Edema • MS/Epilepsy/AD

  31. SubcellularOrganization of the Nervous system selectivemRNA in dendrites (MAP2, no neurofilament) dendriticremodellingwithage Dorsal root ganglion (no dendrites) Amacrinecells (no axons)

  32. Axonal transport • Cytoskeletalproteins • (neurofilament/microtubuli) • Solubleenzymes • Dynein • 0,1 – 4 mm/day

  33. Mitochondria • Membrane-associatedreceptors • Synapticvesicleproteins • Neurotransmitters/Neuropeptides • 100-400 mm/day • Anterograde/Retrograde • Kinesin • Packagedbefore transport

  34. Electrotonic Properties of AxonsandDendrites Basic neuronalfunctions

  35. Spreading of activity? • intrinsicactivity • synapticpotentials • activepotentials • Determines input-output operations of neuron • Passivemembraneproperties, membranereceptors, internalreceptors, synapticallygatedmembranechannels, intrinsic voltage-gatedchannels, second messengers

  36. Electrotonic properties • Cable properties (Rallcompartmental model) if x= λ V/V0= 0.37 But also

  37. Membranepotential • Giant squid axon • Hodgkin and Huxley • Electricallypolarized • Restingmembrane potential-60 mVinside versus outsoide • Action potential: rapiddepolarizationfollowedbyrapidhyperpolarization

  38. Hodgkin and Huxley

  39. For example:

  40. “shunt” effect at equilibrium potential !

  41. Ion pumps • Constant flow of ionsacross the membrane • Ionic pumps • Na+/K+ pump: ATP dependent • Ca2+,Mg2+ ATP ase • Na+-Ca2+exchanger: Na+gradient • Cl-/Na+/HCO3-exchanger

  42. Action potential Increasedconductanceduring action potential. Extracellular Na+concentration ~ amplitude of action potential Action potentialinducedthroughrapidincrease in conductancefor Na+ions? measurment of ioninccurrentsnecessary !!!

  43. Patch clamptechnique • Kenneth Cole (1949)

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