• Mic on
• Zoom share screen, set sound output
• 2nd computer connect to Zoom
• Projector on

http://eyewire.org

• Quiz 1 key (with explanations)
• Exam 1 next Thursday, 9/24
  • 40 questions
• Complete 1 “component/section” in EyeWire, earn 5 extra credit points.
  • Take screen shot, email to Shekoo
  • Due before Friday, 10/16

• Cells of the nervous system
  • Glia
  • Neurons
• How do these cells communicate?

• Old “lore”: ~100 billion neurons
• New estimate (Azevedo et al., 2009)
  • ~86 +/- 8 billion neurons
  • ~85 +/- 9 billion glia
• 100-500 trillion synapses, 1 billion/mm^3

• “Glia” means glue
• Functions
  • Structural support
  • Metabolic support
  • Brain development
  • Neural plasticity?

• “Star-shaped”
• Physical and metabolic support
  • Blood/brain barrier
  • Regulate concentration of key ions (Ca++/K+) for neural communication
  • Regulate concentration of key neurotransmitters (e.g., glutamate)

• Shape brain development, synaptic plasticity
• Regulate local blood flow
• Regulate/influence communication between neurons, (Bazargani & Attwell, 2016)
• Disruption linked to cognitive impairment, disease (Chung, Welsh, Barres, & Stevens, 2015)

• Produce myelin or myelin sheath
  • White, fatty substance
  • Surrounds many neurons
  • The “white” in white matter
• Provide electrical/chemical insulation
• Make neuronal messages faster, less susceptible to noise

• Oligodendrocytes
  • In brain and spinal cord (CNS)
  • 1:many neurons
• Schwann cells
  • In PNS
  • 1:1 neuron
  • Facilitate neuro-regeneration

• Phagocytosis
• Clean-up damaged, dead tissue
• Prune synapses in normal development and disease
• Disruptions in microglia pruning -> impaired functional brain connectivity and social behavior, (Zhan et al., 2014)

• Specialized for electrical & chemical communication
• Post-mitotic – don’t divide
• Most born early in life, (Bhardwaj et al., 2006)
• Among longest-lived cells in body, may scale with organism lifespan (Magrassi, Leto, & Rossi, 2013)
• Can extend over long distances

• Dendrites
• Soma (cell body)
• Axons
• Terminal buttons (boutons)

• Branch-like “extrusions” from cell body
• Majority of input to neuron
• Cluster close to cell body/soma
• Usually receive info
• Passive (do not regenerate electrical signal) vs. active (regenerate signal)
• Spines

• Varied shapes
• Nucleus
  • Chromosomes
• Organelles
  • Mitochonrdria
  • Smooth and Rough Endoplasmic reticulum (ER)

• Another branch-like “extrusion” from soma
• Extend farther than dendrites
• Usually transmit info

• Parts
  • Initial segment (closest to soma, unmyelinated)
  • Nodes of Ranvier (unmyelinated segments along axon)
  • Terminals, axon terminals, terminal buttons, synaptic terminals, synaptic boutons

• Synapse (~5-10K per neuron)
• Presynaptic membrane (sending cell) and postsynaptic (receiving cell) membrane
• Synaptic cleft – space between cells
• Synaptic vesicles
  • Pouches of neurotransmitters
• Autoreceptors (detect NTs); transporters (transport NTs across membrane)

• Functional role
  • Input (sensory), output (motor/secretory), interneurons
• Anatomy
  • Unipolar
  • Bipolar
  • Multipolar

• By specific anatomy
  • Pyramidal cells
  • Stellate cells
  • Purkinje cells
  • Granule cells

• Electrical
  • Fast(er)
  • Metabolically costly
  • Within neurons

• Chemical
  • Slow(er)
  • Metabolically cheap
  • Between neurons, & brain <-> body (via hormones)

• Electrical potential (== voltage)
  • Think of potential energy
  • Voltage ~ pressure
  • Energy that will be released if something changes

• Resting potential
• Action potential

• How to measure
  • Electrode on inside
  • Electrode on outside
  • Inside - Outside = potential

• Neuron (and other cells) have potential energy
  • Inside neuron is -60-70 mV, with respect to outside
  • About 1/20th typical AAA battery
• Like charges repel, opposites attract, so
  • Positively charged particles pulled in
  • Negatively charged particles pushed out

• Ions
• Ion channels
• Separation between charges
• A balance of forces

• Potassium, K+
• Sodium, Na+
• Chloride, Cl-
• Organic anions, A-

• A balance of forces
  • Force of diffusion
  • Electrostatic force
• Forces cause ion flows across membrane
• Ion channels allow ion flow

• Openings in neural membrane
• Selective
• Vary in permeability

• Passive/leak
  • Always open
• Voltage-gated
  • Open/close at certain voltages

• Ligand-gated (chemically-gated)
  • Open/close in presence of special chemicals (ligands)
• Transporters/pumps
  • Move (transport/pump) ions using metabolic energy

• Passive K+ channels open
• [K+] concentration inside >> outside
  • Transporter pumps K+ in
• And then, K+ flows out
  • Force of diffusion

• Organic anions (A-) too large to move outside of cell
• A- and K+ largely in balance == no net internal charge
• K+ outflow creates charge separation: K+ <-> A-
• Charge separation creates a voltage
• Outside +/inside -
• Voltage build-up stops outflow of K+ (before inside/outside concentrations are ==)

• Force of diffusion
  • K+ moves from high concentration (inside) to low (outside)

• Electrostatic force
  • Positive K+ accumulate along outside
  • Negative A- accumulate along inside
  • K+ || A- along membrane creates battery-like voltage
  • Voltage build-up stops K+ outflow

• Specific voltage called equilibrium potential for K+
• K+ positive, so equilibrium potential negative (w/ respect to outside)
• Equilibrium potential close to neuron resting potential

• Resting potential not just due to K+ flow
• Other ions flow
• Resting potential == net effects of all ion flows across membrane

• More on neural communication
• What are the other ions doing?