Notes can be found as interactive webpage at

2: DNA, Synapses, and Neuroanatomy

4: Genes and the History of Molecular Biology #

Overview of History #

  • Mid-1850s:
    • Charles Darwin proposes that all life is deeply related and that there must be some underlying source of variation that is associated with how information is stored and passed on from one generation to the next.
    • Gregor Mendel investigates inheritance in pea plants, which leads to the idea that information needed to build an organism is packaged into a gene – some abstract kind of units associated with specific traits, segregated and sorted in reproduction
  • 1920s: Based on groundwork laid by Max Planck in 1900 and Albert Einstein in 1905, a large group of physicists begin to develop Quantum Mechanics.
  • 1932: Niels Bohr speaks to a group of clinicians in Copenhagen, Denmark, about the limits of investigating structure and function of living organisms at the subcellular level; he speculates that such study could kill the cell.
  • 1935: Max Delbrück publishes “On the nature of gene mutation and gene structure,” in which he proposes that genes are likely to be large molecules. In 1937 he moves to the United States and begins working with bacteria and viruses (called “bacteriophages”) as a way to investigate the physical properties of heredity.
    • Viruses are simple–consisting of protein, nucleic acid, and lipid–yet carry genes to replicate themselves
  • 1944:
    • Erwin Schrödinger publishes What Is Life?, dealing with deep questions concerning the molecular basis of life and drawing attention to Delbrück’s idea that genes are likely to be large molecules. His book inspires a significant number of physicists to research the physical basis of life, a field of study that eventually becomes called molecular biology.
    • Oswald Avery and colleagues publish a report that describes experiments with pneumococcal bacteria demonstrating that DNA can carry genetic information from one cell to another. The report concludes “a nucleic acid of the deoxyribose type is the fundamental unit of the transforming principle” (not protein). His work was essentially ignored by the scientific community, which considered DNA too “stupid” a molecule to carry genetic information.
  • 1952: Alfred Hershey and Martha Chase infect bacteria with T2 phages containing radioactive sulfur atoms (incorporated into protein) and radioactive phosphorous atoms (incorporated into DNA) and showed that it is the radioactive DNA that is transferred to the bacteria during viral infection (more below)
  • 1953: Francis Crick and James Watson propose their famous double-helical structure for the DNA molecule.
    • Realized that genes where sequences of (A,T,C,G)s in DNA and that there was some genetic code between this DNA sequence and the ammino acids in proteins

The Hershey-Chase Blender Experiment #

  • Sought to answer the question: Are Genes Made of Protein or DNA?
  • Steps involved:
    1. Bacteriophage virus T2 is grown on two different media: one containing radioactive sulfur atoms and one containing radioactive phosphorus atoms.
      • Most proteins contain sulfur atoms, while DNA does not; DNA contains phosphorus atoms, while proteins do not.
    2. The viruses are allowed to infect bacteria in a solution with it’s genes, but not given enough time to replicate.
    3. The cells are agitated (bended) enough to dislodge the virus particles from the surface of the bacteria.
    4. Spinning in a centrifuge causes the larger, heavier bacteria to settle into a pellet at the bottom of the tube, while the smaller, lighter virus particles remain in the supernatant liquid.
      • Radioactivity remains in the supernatant, and thus protein stays with the original phages after the infection.
      • Radioactivity is in the pellet, and thus DNA is transferred to the bacteria during the infection; thus, Genes are made of DNA.

5: How Neurons Generate Signals #

  • Diffusion
    • Things tend to spread out from high to low areas of concentration
    • With ions, they diffuse as a function attempting to equalize the concentration difference along with the electrostatic attractions/repulsions
  • Ion channels proteins:
    • Are often gated, sometimes allowing certain substances through
    • Passive; substances move across membrane down concentration gradient so they do not require energy (unlike pumps)
    • This leads to concentration differences of the major ions for neural function
      • Na+, Cl-, Ca++ tend to be more concentrated on the outside of the neuron
      • K+ tends to be more concentrated on the inside
      • This produces a resting potential of -65 millivolts (negative inside) – when no signals are being sent
  • Hyperpolarization: The membrane potential, wrt the resting, becomes more negative when a K+ or Cl- channel open
  • Depolarization: The membrane potential becomes more positive when a Na+ or Ca+ enter

  • Axon hillock: where all dendrites meet, where depolarization first occurs
    • Spatial and temporal summation of neuronal input: superposition of signals from dendrites occur
  • Action potential: The amount of energy needed for a neuron to fire
    • Research done by Alan Hodgkin, Andrew Huxley
    • Voltage-gated ion channels open and close to create this phenomena
    • Action potential propagation along axon with Na+ entering and K+ exiting
      • Sodium-potassium pumps Na+ out of neuron and K+ into neuron to ‘recharge’ the neuron
      • This requires energy in the form of ATP
        • 1 ATP => 3 Na+ out / 2 K+ in
        • 25% of our energy is consumption by human brain
    • Refractory period is the 2-3 ms cooldown where it can’t fire again
  • Myelin coats axons, forming nodes of Ranvier
    • Speeds up propagation via Saltatory conduction
    • Allows the AP to ‘jump’, increasing up signal speed from 10 m/s to 100 m/s
    • Only in vertebrae animals
    • Made up of 40% phospholipid, 30% cholesterol, 30% protein
    • Forming myelin
      • Oligodendrocytes operates in the central nervous system, working on various axons simultaneously
      • Schwann cells operate in peripheral nervous system

6: Synapses, Neurotransmitters, and Receptors #

  • Electrical synapse
    • Gap junction: where ions flow from one to another
    • Connexons: channel
    • Connexins: subunit
  • Chemical synapse:
    • Default synapse people reference
    • Dendritic spine increase the surface area, act as input channel
    • AP propagates down through VG Na+ and K+ channels which trigger the VG Ca++ channels
    • Synaptic vesicle then fuse to membrane-to-membrane to terminals which…
    • Involve neurotransmitters (e.x. serotonin, dopamine) which release into the synaptic cleft
      • Synaptic cleft is ~20nm between in and output
        • Pre-synaptic neuron: axon terminal
        • Post-synaptic neuron: dendritic spine, dendrite, cell body
    • Reuptake transporter reabsorb the neurotransmitter and repackage/resynthesize them
  • Otto Loewi discovered this concept of chemical neurotransmitters
    • Done by triggering the Vagus nerve to slow down a heart in water, then setting another new heart in the same water and finding it slowed down as well
    • Called this Vagusstoff, now known as Acetylcholine
  • Two most common neurotransmitters (NTs)
    1. Glutamate: primary excitatory (more positive, gain of ions) NT in human brain
    2. GABA: primary inhibitory NT in human brain
    • Glutamic acid decarboxylase is an enzyme than can convert glutamate to GABA
  • Two common receptors
    1. Ionotropic receptor / Ligand-gated channel
      • One type of NT receptor protein
      • NT opens the channel, allowing ions through (Ionotropic)
      • Ligand = small molecule that binds to a larger
      1. Ionotropic glutamate receptors
        • Channels for Na+ and Ca++
        • Produces EPSP: excitatory post-synaptic potential
      2. Ionotropic GABA receptors
        • Channels for Cl-
        • Produce IPSP: inhibitory post-synaptic potential
    2. Metabotropic receptor, GPCR: G-Protein coupled receptor
      • NT trigger the GPCR which activates G-protein which interact with…
      • Effector Enzyme makes cAMP which can interact with..
      • Protein Kinase which activate substrate proteins causing cellular effects
      • This is very complex intracellular messaging

7: Neuroanatomy and Excitability #

  • CNS: Brain, Spinal Cord
  • PNS: Everything else; e.x. sensory systems, muscles/movement, autonomic
    • Cranial nerves: 12 nerves that connect the (periphery) senses to the brain
      • Four biggies: olfactory, optic, auditory/vestibular, and vagus nerve
    • Autonomic nervous system: Regulate automatic processes (i.e breathing, heart beat)
      • Sympathetic: Stimulatory, ‘fight or flight’, effects:
        • Increase heart rate, blood pressure
        • Dilates lung airways, pupil
        • Constricts bladder
        • Decreases intestinal mortality
        • NT: norepinephrine
      • Parasympathetic: Inhibitory effects (opposite of those above)
        • NT: acetylcholine
  • Drug molecules: molecules that have an impact on the physiology of the body
    • Agonist: Chemical that triggers NT receptor
      • Sympathomimetic
      • Parasympathomimetic
    • Antagonist: Chemical that blocks NT receptor
      • Sympatholytic
      • Parasympatholytic
  • Monoamine Neurotransmitters: nerve fibers emerge from small clusters of cells in the brainstem yet innervate the whole brain
    • Acetylcholine:
      • Used in the neuromuscular junction (NMJ)
      • Found in relatively small proportionally in brain in the Basal Forebrain Nuclei & Midbrain Pontine Nuclei
    • Serotonin: ~100-200k found in the raphe nuclei
      • Made from tryptophan (amino acid)
    • Dopamine: found in the ventral tegmentum & substantia nigra
    • Norepinephrine: found in the locus coeruleus
  • Peptide neurotransmitters:
    • Made up of chains of ammino acids joined by peptide bonds
    • E.x. endorphins (opioids peptides), substance P
  • Seizure: run-away neural activity in the brain
    • Characterized by aura, muscle convulsions/spasms, amnesia, loss of consciousness
    • Causes of seizures:
      • Idiopathic – underlying cause is not known
      • Genetic and developmental components
    • Associations / factors – all vary widely person-to-person
      • Physical trauma
      • Infection, fever, tumor
      • Emotional stress
      • Sleep deprivation
      • Drug use/withdrawal
      • Intense sensory stimuli
    • Medication: all involve reducing neural excitability
      • Inhibit voltage-gated sodium/calcium/potassium channels
      • Activate GABA receptors
      • Block glutamate receptors
    • Prevalence: 1% ~ 3 million people have it; 30% continue even with medication
    • Surgical treatment:
      • Severing of corpus collosum (rare)
      • Excision of epileptogenic brain tissue
      • Brain electrical stimulation