Brain myths popular science presentation לחוג הירושלמי

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  • לשאול פיזית! "תרימו יד..."100 billion? 30 billion? 86 billion? 115 billion?10:1 Glia? לשאול את עדין ומשרל את זה ספציפית!!!! עד המחקרים של H&H לא היו ספירות מדויקות של כמות התאים או כמות כל סוג של התאים במוח!
  • האם המוח "ייחודי" או מיוחד?
  • לא ידעו לפניכן כמה תאים\\נוירונים! לא ידעו כמה גליה!
  • uses sections and estimates the total number of cells from the number of cells sampled from spaces covering the entire region of interest in 3d .Another way: multiply (counted) average cell density with the volume of the investigated region of interest (estimated with the Cavalieri estimator)לוקחים חתך דק, סופרים תאים ליחידת נפח (סופרים בתלת מימד) וע"פ זה והכפלה הצפיפות בנפח מעריכים כמותDensity x Volumeבעיות: מניב הערכה. שינויים בתוך אותו אזור. קשה לביצוע. דורש מיומנות רבה. הרבה מקום לטעויות אנוש. לא עובד לניתוח מוחות שלמים, רק אזורים (שדורשים הגדרה).
  • 1. I = הרקע התיאורטי
  • לכל תא גרעין תא אחד.אנטיגן שמתבטא רק בתאים נוירונאליים– בגרעין תא (וקצת בציטופלזמה שלהם). לא מתבטא ב:cerebellar Purkinje cells, olfactory  and retinal photoreceptorsneuron-specific nuclear protein (Nuclear Proteins - Proteins found in the nucleus of a cell.) :NeuN (Neuronal Nuclei).
  • Homogenization: cells are mechanically disrupted, releasing  organelles and cytoplasmThe tissue of interest is dissolved by mechanical dissociation in detergent and transformed into an isotropic suspension of known volume that contains all the cell nuclei present in the originalVat = גיגית
  • A – DAPI StainedB – NeuNImmunoreactivity
  • 4 Rat Brains counted. 2-3 months old.
  • 4 Healthy male adult brains. ~50 (x3) + 71 (had more neurons) years old. Whole brain numbers. Cortex. Neuron count. Cerebellum.
  • מדובר על היחס בין : ratio of the total cortical surface (if it was flat and unfolded) to total exposed cortical surface.מוח גדול יותר נהיה מקופל יותר.
  • No! Smaller than elephant, whale, dolphin..
  • “Ok, what about more sophisticated/normalized comparisons? Such as Encephalization..”
  • שיטה allometry = the science of relating quantitatively the size of one part of the body to another"encephalization quotient" ( "EQ"), measures ratio of an animal's brain and body size relative to other, similarly sized animals
  • NO to Both!Capuchin is much smarter than Capybara (rodent) – Different Cellular scaling rules!Gorilla is much smarter than Capybara – larger.
  • “The ONLY Brain That Studies Brains!”
  • אוכלי חרקיםInsectivores: Hypermetric for Cortex, Linear for Cerebellum.
  • Brain myths popular science presentation לחוג הירושלמי

    1. 1. NEURON: Glial cells are nerve cells that dont carry nerve impulses. Include: Immune system, support, nutrients..
    2. 2. 5 BRAIN MYTHS: #1 YOU ONLYUSE 10 % OF YOUR BRAIN.NO! Evidence1. : fMRI. PET scans.2. Effects of Damage.3. Evolution.(Wasted space)
    3. 3. 5 BRAIN MYTHS:MYTH #2: BIGGER = BETTER BRAIN The bigger = better relationship collapses, when Humans 1.5kg comparing species across orders . Elephants 5.6kg •Cows have larger brains than just about any Whales 7.8 kg species of monkey.. •Capybara & Capuchin monkey..MYTH #3: HUMAN BRAINS ARE THERELATIVELY LARGEST1. Brain/body mass ratio2. Encephalization quotient
    4. 4. MYTH #4: BIGGER BRAIN = MORENEURONS THAN A SMALLER BRAIN neuronal density = # neurons relative to mass of brainMYTH #5: 100 BILLION NEURONSNeurons are the fundamental building blocks of any nervoussystem. These cells, tree-like branches which reach out with theirneighbors, forming vast electrical and chemical network that is ourbrain. Its our neurons that allow our brains to do all of these thingsmore rapidly and efficiently than any machine.
    5. 5. DEAR (FUTURE) SCIENTISTS, WHO CAN TELL ME: How Many Cells in the brain?  % Neurons? 10%? 25%?  % Glia? 90%? 1%?
    6. 6. I. Comparative Brains:Isotropic Fractionation +FindingsII. Is the Human Brain Neuroanatomically Unique?
    7. 7. “There was, to our knowledge,no actual, direct estimate ofnumbers of cells or of neuronsin the entire human brain to becited until 2009”.“It is commonly assumed that gliaoutnumber neurons in the brain andspecifically in humans by a factor of 10 or50 despite the lack of data for theseassumptions = {Kandel, 2000} .Azevedo, Herculano-Houzel, Lent et al. (2009). Equal numbers of neuronal and nonneuronal cells make thehuman brain an isometrically scaled-up primate brain. The Journal of comparative neurology, 513(5), 532-41.
    8. 8. Optical Fractionation:Count average cell density, multiply by volume of investigated “slice”. Problems: ”Estimate cell count” (Looks at regions, not whole) Different regions -different densities # Reached by {cell} Density X Volume. This is not an independent variable and cannot be used in statistical comparisons against volumeStereology.Info, MBF Bioscience; West 1999
    9. 9. THE ISOTROPIC FRACTIONATOR1. Method I. Theoretical basis. II.How it works.2. Benefits3. Findings: a. Rats & Glia b. Humans.
    10. 10. ISOTROPIC FRACTIONATION THEORETICAL BASIS: 2 AXIOMS 1. 1 Cell = 1 Nucleus 2. NeuN - neuronal nuclei specific proteinIso = EqualMullen, et al. (1992). "NeuN, a neuronal specific nuclearprotein in vertebrates". Development 116;
    11. 11. ISOTROPIC FRACTIONATIONHOW IT WORKS (I):A. “Slice” Preserved Brain (Or structures)B. “Stir” (Homogenize + Centrifugate)C. DAPI (DNA dye) Stain.D.“Pour” homogenate+DAPI into Vat(s) in a isotropic suspension
    12. 12. ISOTROPIC FRACTIONATION HOW IT WORKS (II): Arrowheads = NeuN negative (=Glia)E. Extract (8+) aliquots ( ) A: DAPIF. Count with hemocytometer(= microscope counting).Total Cell # = Nuclei Density X VolumeG. Add NeuN specific Antigen(Mark Neurons).H. Count “Neurons” (NeuN+)Glia Cell# = Total Cell# - #NeuN+ B: NeuN
    13. 13. ISOTROPIC FRACTIONATION BENEFITS:Absolute, Less room for human error.accurate Can Analyze whole brain, not justquantitative slices or regions.count of Yields absolute Cell CountNeurons, Glia independent of Brain Volume/Mass.
    14. 14. ISOTROPIC FRACTIONATION FINDINGS (I): Rat Brain: Rat brain: ~331.65 million cells No correlation between Brain Cerebellum: 70% of Weight & Cell #! Neurons. 60% Neurons (140,000,000) (200,000,000) (±17% ~ ±3% ) X5 as the Cortex! More Neurons Than Glia!!!!Herculano-Houzel and Lent; Isotropic Fractionator: A Simple, Rapid Method for theQuantification of Total Cell and Neuron Numbers in the Brain; Journal of Neuroscience, 2005
    15. 15. FINDINGS (II): - HUMANS:
    16. 16. FINDINGS (III): - HUMANS:Our brain has 86 ± 8 billion NeuN+ (“neurons”) and ~84.6 billion “Glia”. NOT 100 Billion!• More Neurons than Glia! Nonneuronal/Neuronal ratio = 0.99 for whole human brain.• Cerebral Cortex: contains just 19% of neurons despite size and mass (82%)!• Cerebellum: Just 10% of brain mass, But ~69 billionNeuronal and Nonneuronal Cells Make the Human Brain an Isometrically Scaled-UpEqual Numbers of neurons - 80%!Primate Brain; HERCULANO-HOUZEL et al., J. of Comparative Neurology, 2009
    17. 17. IS THE HUMAN BRAINUNIQUE?“we have brains that are bigger thanexpected for an ape, we have a neocortexthat is three times bigger than predicted forour body size, we have … areas of theneocortex and cerebellum that are largerthan expected..” (Gazzaniga, 2008).“The only brain that studies brains”
    18. 18. CORTEX SIZE“Oversized Neo-cortex” - 82%of the Brain’s mass.The cortex contains only 19%of neurons!Cerebellar cortex & CerebellumSize = Same relative size as ApesBUT! Mass =!>Neuron “No Correlation of Variance between Brain Weight & # neurons!“ (Semendeferi, 2001)
    19. 19. CLAIMS OF HUMAN UNIQUENESS: CORTICAL FOLDING? No!The folding ratio increases along with overallbrain volume Humans: 2.86; Dolphins and whales- 4.0 - 8.55..Von Bonin (1941); (Macphail, 247)
    20. 20. CLAIMS OF HUMAN UNIQUENESS: BRAIN SIZEAbsolute Size?
    21. 21. CLAIMS OF HUMAN UNIQUENESS: BRAIN/BODY MASS RATIOHumming bird: 1/25Squirrel monkeys: 1/20Mice: 1/40Humans: 1/49Dolphins: ~1/80Cats: 1/100Dogs: 1/125Lions: 1/500Elephants: 1/560Horses: 1/600Sharks: 1/2500 Kuhlenbeck (1973)
    22. 22. CLAIMS OF HUMAN UNIQUENESS: ENCEPHALIZATION Encephalization Quotient : E.Q>1 : bigger brain than expected. Human E.Q ~ 7Jerison (1973)
    23. 23. CLAIMS OF HUMAN UNIQUENESS: ENCEPHALIZATION“A brain 7 times too large for amammal of its size…”(Marino, 1998)(Jerison, 1973).(Macphail, 243)
    24. 24. CLAIMS OF HUMAN UNIQUENESS: ENCEPHALIZATION No! • The expected body–brain ratio depends on the Species compared! • Compared to Primates: E.Q of 3 • Compared to small monkeys: E.Q 1.1! “gorillas and orangutans, rather than humans, are outlier species in terms of body size” {Brain: 1% vs 2% of body mass} (Semendeferi and Damasio, 2000)(Barton, 2006; Herculano-Houzel et al.,2007).The human brain in numbers: a linearly scaled-up primate brain; Herculano-Houzel, 2009
    25. 25. WHAT MATTERS:RELATIVE OR ABSOLUTE BRAIN SIZE ? Absolute? Capybara vs Capuchin Monkey: Relative? Gorilla Vs Capuchin(Roth and Dicke, 2005)
    26. 26. WHAT MAKES US SPECIAL? 1. Absolute Number of Neurons. Why? 2. We Have the Largest PRIMATE Brain!Different Specie Orders’Brains SCALEDifferently! *Primates Vs Rodentia VsInsectivores…
    27. 27. WHAT MAKES US SPECIAL:BIGGEST PRIMATE BRAIN3. (Efficient) IsometricPrimate Brain Scaling.“Primate brain size increasesisometrically as a functionof neuron number”.Rodents – Hypermetric X10 neurons inIncrease. Primates  X11 larger - “average neuronal size brain.increases together withneuronal number, but not in X10 neurons in rodentsprimates”  X35 larger brain.Linear, economical cellular scaling rules apply to primate brains. Herculano-Houzel et al, Natl Acad Sci USA (2007).;Equal Numbers of Neuronal and Nonneuronal Cells Make the Human Brain an Isometrically Scaled-Up Primate Brain. Herculano-Houzel et al. Journal of Comparative Neurology 513:532–541 (2009)
    28. 28. POTENTIAL SOURCES OF HUMAN SPECIALNESS: • Neuroanatomical regions (Area 10 Prefrontal, specific layers of cortex..) • Lengthy infant Development (Increased Learning Plasticity/development). • Connectivity (Dendritic connection density..) • Genes. • Special Cellular traits • Absolute # Neurons • …

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