Source: Textbook Chapters 4–6, Lecture Notes
Tags: DNA, double helix, gene transcription, translation, Hershey-Chase, action potential, ion channels, myelin, saltatory conduction, synapse, neurotransmitter, glutamate, GABA, EPSP, IPSP, ionotropic, metabotropic, GPCR, UC Berkeley, Brain-Mind Odyssey
Chapter 4 traces how scientists figured out that DNA (not protein) carries genetic information, from Darwin and Mendel through the discovery of the double helix. Chapter 5 explains how neurons generate electrical signals: resting potential, ion flow, action potentials, and myelin. Chapter 6 covers how neurons talk to one another via synapses, neurotransmitters, and two types of receptors (ionotropic and metabotropic).
Gene
The fundamental unit of heredity. Represented as a sequence of nucleotides.
Double helix
The structure of DNA, discovered in 1953 by Watson and Crick with critical X-ray data from Rosalind Franklin. Two strands held together by hydrogen bonds.
Gene transcription
Copying the DNA nucleotide sequence into messenger RNA (mRNA). "Transcription" = making a copy.
Gene translation
Converting the nucleotide sequence information in mRNA into a sequence of amino acids to build a protein.
Nucleotide codons
Triplet sequences of nucleotides that each correspond to a specific amino acid. This mapping is the genetic code.
Hershey-Chase experiment
Demonstrated that DNA, not protein, carries genetic information. Used bacteriophage T2. Labelled protein with sulfur (red) and DNA with phosphorus (green). After injection into bacteria and centrifugation, phosphorus (DNA) appeared in daughter cells.
Diffusion
Particles move apart and distribute uniformly over whatever volume of fluid is available. The basic mechanism by which ions move through open channels.
Ion channel
A membrane protein that allows specific ions to pass through when the channel is open.
Ion pump
Uses energy (ATP) to move specific ions from one side of the membrane to the other, against their concentration gradient.
ATP (adenosine triphosphate)
The intracellular energy currency. Adenosine is also a component of DNA. Food is metabolised to glucose, which generates ATP.
Resting membrane potential
The voltage across a neuron's membrane at rest: approximately -65 millivolts.
Hyperpolarization
The cell becomes more negative (greater magnitude of charge separation). Occurs when Cl- flows in or K+ flows out.
Depolarization
The cell becomes more positive (smaller magnitude of charge separation). Occurs when Na+ or Ca2+ flows in.
Action potential
A rapid, all-or-none change in membrane voltage that propagates along the axon. Once initiated, it travels the full length of the axon without stopping.
Voltage-gated ion channels
Sodium and potassium channels located along the axon that open and close in sequence during an action potential. Na+ channels open first (fast), then K+ channels open (slow).
Refractory period
The recovery period (1–2 milliseconds) after an action potential, during which the neuron cannot fire again. Prevents reverse propagation and reverberation of the nerve impulse.
Na+/K+ pump
Pumps 3 Na+ out and 2 K+ in per cycle, using ATP. These are not ion channels. They restore the concentration gradients after action potentials.
Axon hillock
The junction between the soma and the axon. Has the highest density of ion channels and is where the action potential begins.
Myelin
Glial cells that wrap around axons. Composition in human CNS: ~40% phospholipid, ~30% cholesterol, ~30% protein. Speeds up nerve impulse propagation.
Nodes of Ranvier
Small gaps along a myelinated axon between segments of myelin. The only places where ion channels are exposed and ions can diffuse in and out.
Saltatory conduction
Action potential "jumps" from one node of Ranvier to the next. Like an express train. Dramatically increases conduction speed.
Oligodendrocytes
Glial cells that produce myelin in the central nervous system.
Schwann cells
Glial cells that produce myelin in the peripheral nervous system.
Synapse
The junction between two neurons. "Synapse" comes from Greek meaning "to fasten together."
Chemical synapse
Neurons separated by a synaptic cleft. Signal crosses via neurotransmitter release.
Electrical synapse (gap junction)
Built from connexon channels (composed of connexin proteins) that directly connect the interiors of two adjacent cells.
Neurotransmitter
A chemical messenger released from synaptic vesicles at the axon terminal into the synaptic cleft.
SNARE complex
Attachment proteins that cause synaptic vesicles to fuse with the axon terminal membrane, enabling neurotransmitter release (exocytosis).
Neurotransmitter inactivation
Two mechanisms: reuptake (transporter proteins remove neurotransmitter from the cleft) or enzymatic degradation (only occurs with acetylcholine).
Glutamate (glutamic acid)
The most abundant excitatory neurotransmitter in the brain. Glutamatergic cells are found everywhere in the brain.
GABA (gamma-aminobutyric acid)
The most abundant inhibitory neurotransmitter. Made from glutamic acid by the enzyme glutamic acid decarboxylase (GAD). The pathway: glutamate → GAD → GABA.
EPSP (excitatory postsynaptic potential)
Depolarization of the postsynaptic cell. The inside becomes more positive. Caused by Na+ or Ca2+ flowing in.
IPSP (inhibitory postsynaptic potential)
Hyperpolarization of the postsynaptic cell. The inside becomes more negative. Caused by Cl- flowing in or K+ flowing out.
Ionotropic receptor (ligand-gated channel)
A neurotransmitter receptor that directly opens an ion channel when a neurotransmitter binds. Faster response.
Metabotropic receptor (GPCR)
G-protein coupled receptor. Binding does not directly open an ion channel. Instead, it activates a G-protein, which splits and affects effector enzymes, intracellular messengers, ion channel states, or gene transcription. Slower but more diverse response.
Otto Loewi
Discovered chemical neurotransmission using two beating frog hearts. Identified "Vagusstoff" (the substance released by the vagus nerve) as acetylcholine, the first neurotransmitter discovered.
Four molecular building materials for life: lipids, proteins, carbohydrates, nucleic acids
Key sequence of discovery:
Charles Darwin proposed evolution
Gregor Mendel (Austrian, originally studied astronomy) investigated inheritance with pea plants
Quantum mechanics era: Einstein, Planck, Bohr, Curie, Heisenberg, Schrödinger
Bohr: in observing nature, we change it
Schrödinger wrote What Is Life? (1944), addressing the molecular basis of life
Pauling was ill and bored, which led him to discover the alpha helix
For a time, scientists thought genes were made of protein. DNA was dismissed as "the stupid substance."
Oswald Avery demonstrated that DNA carries genetic information from one cell to another
Hershey-Chase experiment confirmed DNA as the genetic material:
Sulfur labels protein, phosphorus labels DNA
Phosphorus appeared in daughter cells after bacteriophage T2 infected bacteria
Rosalind Franklin's X-ray photograph was critical evidence for the double helix
Watson and Crick published the double helix structure in 1953
The two strands are held together by hydrogen bonds
Central dogma: DNA → (transcription) → mRNA → (translation) → protein
Wendell Stanley (Stanley Hall at Berkeley): showed viruses can be crystallised; viruses inject DNA into bacteria, which then burst with new virus particles
Max Delbrück and Lise Meitner: originally studied astronomy and theoretical physics, then biology. Atomic fission.
Robert Oppenheimer: head of the Manhattan Project at Los Alamos
Edward Tolman (UC Berkeley psychology faculty): studied cognitive maps in animals (hippocampus). Led resistance against an anti-communist loyalty oath; was fired. The oath still exists today.
Pauling was suspected of being a communist for opposing nuclear weapons testing
Key ion concentrations:
Higher outside the cell: Na+, Cl-, Ca2+
Higher inside the cell: K+
Resting membrane potential: -65 mV
Measurement technique: place electrodes on either side of the membrane. Octopus/squid giant axons were used because of their large size.
Hodgkin and Huxley used squid giant axons to directly measure voltage changes across the axon membrane during action potentials
Action potential sequence:
Voltage-gated Na+ channels open (fast) → depolarization (upstroke)
Na+ channels close
Voltage-gated K+ channels open (slow) → repolarization (downstroke)
K+ channels close
Brief hyperpolarization (undershoot) before return to resting potential
All-or-none principle: once triggered, the action potential propagates to the end of the axon
The refractory period (1–2 ms) prevents the signal from travelling backwards
Na+/K+ pump restores gradients using ATP: 3 Na+ out, 2 K+ in
Energy facts:
Body burns ~1,440 kilocalories per day
Heart and brain use roughly half the body's energy
~250 calories per day power the Na+/K+ pumps alone
Unmyelinated axon conduction: ~100 m/s
Myelinated axon conduction: ~200 m/s
The electrochemical gradient (combined difference in charge and chemical concentration) drives axon propagation
Louis-Antoine Ranvier discovered the nodes of Ranvier
Chemical synapse transmission sequence:
Action potential arrives at axon terminal
Voltage-gated Ca2+ channels open
Calcium influx triggers exocytosis of synaptic vesicles (via SNARE complex)
Neurotransmitter binds to postsynaptic (and some presynaptic) receptors
Inactivation via reuptake or enzymatic degradation
Synapses can form anywhere on a neuron, not just at dendrites
Cortical neuropil = the closely packed structure of neurons in the cortex
EEG (electroencephalography) records the summed electrical activity of the brain
Glutamate: primary excitatory NT → ionotropic receptors → Na+ and Ca2+ flow in → EPSP (depolarization)
GABA: primary inhibitory NT → ionotropic receptors → Cl- flows in (or K+ out) → IPSP (hyperpolarization)
Conversion pathway: glutamic acid → GAD (glutamic acid decarboxylase) → GABA
To confirm a neuron is GABAergic, check for the presence of GAD
Ionotropic: neurotransmitter binds → channel opens directly → fast, ion-mediated response
Metabotropic (GPCR): neurotransmitter binds → G-protein splits → activates effector enzymes → intracellular messengers → diverse downstream effects (ion channels, gene transcription, metabolism). Slower but amplified response.
⚠️ Hershey-Chase experiment: know the logic (sulfur = protein, phosphorus = DNA) and the conclusion (DNA carries genetic info). This is a classic exam question.
⚠️ Central dogma: DNA → transcription → mRNA → translation → protein. Be able to define transcription and translation separately.
⚠️ Know the ion concentration asymmetries: Na+, Cl-, Ca2+ higher outside; K+ higher inside.
⚠️ Action potential sequence: Na+ channels open (depolarize) → Na+ channels close → K+ channels open (repolarize) → K+ channels close → undershoot → rest. The graph goes up, peaks, comes down, dips below baseline, returns.
⚠️ Na+/K+ pump: 3 Na+ out, 2 K+ in, uses ATP. These are pumps, not channels.
⚠️ Myelinated vs. unmyelinated conduction speeds (200 m/s vs. 100 m/s) and the mechanism of saltatory conduction.
⚠️ Glutamate = excitatory, GABA = inhibitory. Know the conversion pathway (glutamate → GAD → GABA) and the postsynaptic potentials each produces (EPSP vs. IPSP).
⚠️ Ionotropic vs. metabotropic: be able to compare mechanism, speed, and downstream effects. Know that metabotropic receptors are also called GPCRs.
⚠️ Otto Loewi's frog heart experiment and the identification of acetylcholine as the first neurotransmitter.
Q: What did the Hershey-Chase experiment demonstrate, and how?
A: It showed that DNA, not protein, carries genetic information. They labelled protein with sulfur and DNA with phosphorus in bacteriophage T2, infected bacteria, and found phosphorus (DNA) in daughter cells.
Q: What is the central dogma of molecular biology?
A: DNA is transcribed into mRNA, which is then translated into a protein. Transcription = copying DNA to RNA; translation = converting nucleotide sequence into amino acid sequence.
Q: What is the resting membrane potential of a neuron?
A: Approximately -65 millivolts.
Q: Describe the sequence of ion channel events during an action potential.
A: Voltage-gated Na+ channels open first (depolarization), then close. Voltage-gated K+ channels open next (repolarization), then close. There is a brief undershoot (hyperpolarization) before return to resting potential.
Q: What is the refractory period, and why does it matter?
A: The 1–2 millisecond recovery period after an action potential during which the neuron cannot fire again. It prevents the signal from propagating backwards and stops reverberation.
Q: How does the Na+/K+ pump work?
A: It uses ATP to pump 3 Na+ ions out of the cell and 2 K+ ions into the cell per cycle, restoring the concentration gradients needed for future action potentials.
Q: What is saltatory conduction?
A: In myelinated neurons, the action potential jumps from one node of Ranvier to the next, dramatically increasing conduction speed. Positive ions inside the axon repel each other until they reach the next exposed node.
Q: What is the difference between an EPSP and an IPSP?
A: An EPSP is depolarization of the postsynaptic cell (more positive inside, caused by Na+ or Ca2+ influx). An IPSP is hyperpolarization (more negative inside, caused by Cl- influx or K+ efflux).
Q: How is GABA synthesised from glutamate?
A: Glutamic acid is converted to GABA by the enzyme glutamic acid decarboxylase (GAD).
Q: What is the key difference between ionotropic and metabotropic receptors?
A: Ionotropic receptors are ligand-gated ion channels that open directly when a neurotransmitter binds (fast response). Metabotropic receptors (GPCRs) activate intracellular signalling cascades via G-proteins, producing slower but more diverse effects including changes to gene transcription.
Q: Who discovered chemical neurotransmission, and how?
A: Otto Loewi, using two frog hearts. He stimulated one heart's vagus nerve, then transferred the surrounding fluid to a second heart, which slowed without direct stimulation. The chemical substance was acetylcholine ("Vagusstoff").
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