survey of neural basis (exam 1)

Aristotle — what did he believe about the brain, and why?

He did not believe the brain controls behavior. His evidence: cut a chicken's head off and it still runs; some insects live up to six weeks headless. • The resolution: the spinal cord contains preprogrammed neural networks that pattern frequently used movements (running, swimming). • Insects have ganglia — clusters of cell bodies outside the CNS, in every body segment, capable of basic reflexes. || TIP: A headless body moves by REFLEX, not brain-controlled behavior.

Galen — his contribution to brain science

Physician to the gladiators in Rome. He noticed that people with head/brain injuries were different after they recovered. — Credited as the origin of modern brain science. || TIP: Brain LESION DAMAGE is how we learned most early information about what brain areas do.

Fritsch & Hitzig — name their THREE findings

German medical students, 1870. Anesthetized dogs, removed the skull (dorsal view), applied very low voltage with portable batteries. • 1. The brain is electrically excitable • 2. Regional specificity — different spots move different muscle groups (one-to-one mapping) • 3. Replicable — same place, same body part, every time || TIP: Middle of brain → movement on the CONTRALATERAL side. Back of brain → nothing visible (it processes vision — dogs can't report it).

Robert Bartholow — what did he show, and what were the consequences?

1874, Cincinnati. Patient Mary Rafferty had a 2-inch hole in her skull from a cancerous ulcer, leaving her brain exposed. He stimulated it — same result as Fritsch & Hitzig, but she was awake and could report back. — He told her not to move her hand — she could not override it. • First experimental evidence the brain is electrical AND controls behavior • It works in humans, not just animals • Continuity of brain organization across species • Therefore animal research is valid for understanding humans || TIP: ETHICS: Mary Rafferty died days later. Bartholow was run out of town. The AMA then banned human experimentation that disregards saving the patient's life.

Wilder Penfield — method and findings

Canadian neurosurgeon treating severe epilepsy. Numbed the skull with Novocaine, removed a piece, and stimulated the brain while talking to the awake patient. • Back → flashes of light / fireworks (visual cortex) • Lateral sides → hearing sounds • Midline → arm movement • Replicable from person to person || TIP: THE BIG ONE: stimulation elicited MEMORIES AND EMOTIONS — patients heard the auditory memory of "Jingle Bells," not random tones.

Michael Gazzaniga — split-brain studies

Severed the corpus callosum (the white-matter band letting hemispheres communicate) in patients with intractable epilepsy — seizures not responsive to drugs, starting in areas that couldn't be removed. Goal: corral the seizure in one hemisphere. • Left hand feels an object → info goes to the right hemisphere → cannot name it (language is left) • Right hand feels an object → left hemisphere → can name it || TIP: PATIENT P.S.: "girlfriend" flashed to his LEFT visual field (right hemisphere). He couldn't SAY her name — but spelled "Liz" with Scrabble tiles using his left hand.

Gall and Spurzheim — phrenology

Franz Joseph Gall proposed that mental faculties (wisdom, satire — he settled on 27) are localized to specific cortical spots, and that a larger area creates a bulge you could feel through the skull. — Spurzheim, his assistant, coined the term phrenology and removed the negative faculties to make it more marketable. || TIP: The fatal flaw: NO EMPIRICAL EVIDENCE. Skulls are basically smooth. By 1840 phrenology was parlor humor.

Flourens — how did he discredit phrenology?

He attacked Gall with the most valuable weapon: empirical evidence. — He surgically removed the proposed "amorous relations" bump from a female cat. If Gall were right, she'd lose interest in romance. She had kittens anyway. — Concluded moral/intellectual faculties can't be localized to the cortex.

Paul Broca and patient "Tan"

Broca found a 51-year-old patient who had been unable to speak for 20 years (known as Tan). On autopsy, damage sat exactly where Bouillaud and Aubertin had predicted — now Broca's area, in the frontal cortex. || TIP: Gall was ridiculed; Broca was celebrated. Same idea (localization) — but Broca had ACTUAL BRAIN DAMAGE as evidence.

Camillo Golgi — his theory and his contribution

Theory (WRONG): nerve net theory — the nervous system is one continuous, connected network; neurons touch. — Contribution (huge): invented the silver stain — a histological technique that let scientists see whole neurons for the first time. || TIP: THE IRONY: Golgi's own stain disproved Golgi's own theory — and he still defended the nerve net at the 1906 Nobel ceremony where he SHARED the prize with Cajal.

Santiago Ramón y Cajal — the neuron doctrine

Theory (RIGHT): the neuron doctrine — each neuron is a discrete, physically separate unit. Neurons do not touch; there's a gap between them. — An artist, he used Golgi's stain and drew neurons in such detail that his drawings are still considered accurate today. || TIP: MEMORY HOOK: Golgi = Glued together. Cajal = Cut apart.

Hodgkin & Huxley — what did they do?

Two English scientists (published 1950s, Nobel 1963). Where earlier scientists stimulated the brain with electricity, they set out to record the neuron's own inherent electrical activity. — Used the squid giant axon. Recorded both the resting potential (−70 mV) and the action potential. || TIP: The Nobel wasn't just for recording it — it was for EXPLAINING WHAT HAPPENS AT EVERY STEP.

Otto Loewi — what did he prove?

Proved that synaptic transmission is CHEMICAL, not an electrical spark jumping the gap. — 1921 — a dream gave him the perfect experiment (the frog heart). Working alongside Henry Dale, who was studying acetylcholine. || TIP: This is why acetylcholine — discovered at the neuromuscular junction — was the FIRST neurotransmitter identified.

Walther Nernst — what does the Nernst equation predict?

It predicts the equilibrium voltage for ONE ion at a time, based on that ion's concentration inside vs. outside the cell. — V = ±60 · log(ion outside / ion inside) — It tells you the voltage at which that ion would be "happy" — its chemical and electrical gradients balanced — if it moved freely.

Sherrington and Adrian — their contributions

Charles Sherrington — coined the term synapse (Greek "to clasp") in 1897, formalizing the gap Cajal had proposed but couldn't see. — Edgar Adrian — discovered evidence for the all-or-none law. They shared the 1932 Nobel Prize.

The left-brain / right-brain personality myth

FALSE. The idea that the left brain is analytic and the right brain is creative is not accurate at all. — We use all of our brain, all the time — every neuron. What matters is the interconnections, not which side, and this looks different from person to person.

Nissl stain — what does it stain, and what did it reveal?

Stains the endoplasmic reticulum, which means it only visualizes CELL BODIES — not the whole neuron. • Revealed regional differences in cell-body distribution → different areas of the brain have different functions • Showed there is more than one kind of cell || TIP: Brodmann later used Nissl staining to map the cortex into layers by cell type.

Golgi stain — what does it stain, and why was it revolutionary?

The stain is taken up by the ENTIRE neuron — cell body plus all its processes. — Revolutionary because for the first time you could parcel out individual neurons and see their complete shape: a distinct cell body with projections. || TIP: It's also what showed us that axons and dendrites LOOK DIFFERENT from each other.

How is a Golgi stain different from a Nissl stain? (exam review question)

Nissl stains the endoplasmic reticulum, so it only visualizes CELL BODIES. Golgi stain is taken up by the WHOLE CELL, so the entire neuron can be visualized. — That's what made Golgi revolutionary — you could finally see a neuron's full structure, not just where its cell body sat. || TIP: Watch for reversed answer choices that swap which stain does which.

Anterograde tracing — how does it work and what does it tell you?

Inject the dye into a region → the cell bodies take it up → it travels down the axon using the cytoskeleton → deposits at the synapses/terminals. — Tells you where that neuron PROJECTS TO. || TIP: ANTEROGRADE = FORWARD, the normal direction a neuron works (information flows down and away from the cell body).

Retrograde tracing — how does it work and what does it tell you?

Inject the dye where the axon terminals end → the terminals pick it up → it's transported backwards up the axon → lodges in the cell body. — Tells you which cells were TALKING TO that area. || TIP: RETROGRADE = BACKWARDS, against the normal flow — a direction the neuron doesn't normally work.

CT scan vs. PET scan

CT — uses X-rays → shows STRUCTURE. An X-ray beam circles the head producing 2D horizontal images. — PET — inject radioactive glucose; active areas metabolize it → shows FUNCTION in real time. || TIP: Straight off the exam review slide. X-rays = structure. Radioactive glucose = function.

MRI vs. fMRI vs. DTI

MRI — powerful magnetic field → high-resolution STRUCTURE. — fMRI — measures blood flow + oxygenation → FUNCTION. No radioactivity (safer/cheaper than PET), but subjects must hold very still. — DTI — tracks water movement to map white-matter pathways (the communication network). || TIP: fMRI's rise created the field of COGNITIVE NEUROSCIENCE. Its big lesson: even simple tasks activate widespread areas.

EEG — what does it measure?

Electroencephalography. Electrodes placed at regular intervals on the scalp detect the electrical activity of large populations of brain cells. Amplified and recorded. — Used for seizures, sleep studies, and task-related activity. || TIP: Normal brain activity is ASYNCHRONOUS. During a seizure it becomes SYNCHRONOUS — huge coordinated peaks and valleys.

"Gains in the brain are all about the stain"

Dr. Clabough's phrase for a core principle: you can only see as much information as your tool allows you to see. — Being able to visualize neuronal processes — and to see some neurons selectively and not others — is what moved the whole field forward. || TIP: Same lesson as Golgi's silver stain: the TECHNIQUE enables the discovery, even when the theory is wrong.

Contralateral vs. ipsilateral

Contralateral = OPPOSITE side ("contra" = against). The right hemisphere controls the left side of the body. — Ipsilateral = SAME side. || TIP: Most sensory and motor information CROSSES — it's contralateral. This is what Fritsch & Hitzig saw in dogs and what makes split-brain results so striking.

Dorsal, lateral, sagittal, coronal — what does each view show?

• Dorsal view — looking top-down (you can see both hemispheres and the split between them) • Lateral view — from the side • Sagittal section — cut down the midline, front to back (how you see the hypothalamus and corpus callosum) • Coronal section — a front-facing slice, "like where you'd wear a crown"

Localization of function — language and face recognition

Language is on the LEFT for ~90% of right-handed people. Not universal — it differs for many left-handers and can be right-sided or bilateral. — Facial recognition tends to be on the RIGHT for most people. || TIP: MNEMONIC: "Language" and "Left" both start with L. Face → Right.

Soma (cell body) — what's in it, and how much of the neuron is it?

The cell body, 5–100 micrometers across. Contains the standard microorganelles: nucleus, ribosomes (make protein from RNA), endoplasmic reticulum (processes and packages protein), mitochondria (energy), cytoskeleton (structure and transport). — Despite being the visual centerpiece of every diagram, it's only ~4–10% of the neuron's total surface area. || TIP: The nervous system uses a LOT of energy — hence all those mitochondria. The brain consumes ~20% of the body's energy.

Dendrites — four identifying properties

The INPUT side — dendrites RECEIVE information. From the Greek for "tree." • Fine and thin • Bumpy — covered in dendritic spines • Branches come off at ACUTE angles • Account for the bulk of the neuron's surface area || TIP: More surface area = more connections = more information received.

Axon — four identifying properties (and how it differs from a dendrite)

The OUTPUT side — carries the message AWAY from the soma. • Big and thick (a single process) • Smooth — no spines • Collaterals come off at RIGHT angles • Connects to the cell body at the axon hillock; ends at the axon terminal (terminal bouton) || TIP: THE IMAGE: a dendrite is a TREE (thin, bumpy, acute branching). An axon is a CABLE with taps (thick, smooth, right-angle collaterals).

Dendritic spines — what are they and why do they matter?

Small protrusions extending from the dendrites. A single neuron may have thousands. • They're where information is received — most incoming signals land here • They dramatically increase surface area, so more information can come into the cell • Shapes: thin, stubby, mushroom • They're PLASTIC — they change shape with experience (denser in enriched-environment and pregnant rats)

Axon hillock — what happens there and why?

The junction where the axon meets the cell body — the "entrance gate." — This is where the action potential is GENERATED. It's loaded with sodium-potassium pumps, making it extremely sensitive — "hair-trigger ready." — It's also where all the incoming signals are integrated to decide whether to fire. || TIP: Don't confuse it with the AXON TERMINAL at the other end, where vesicles live and neurotransmitter is released.

Multipolar, bipolar, unipolar neurons

Classified by the number of processes extending from the soma: • Multipolar — many dendrites + one axon. The most common type. • Bipolar — two processes (one dendrite, one axon). Mostly sensory. • Unipolar — one process that splits into axonal and dendritic segments. Mostly sensory.

Astrocytes — name their functions

Star-shaped, the most abundant glial cell. They: • Fill the spaces between neurons • Transport nutrients from blood vessels to neurons • Maintain a constant chemical environment • Clean up debris from dead cells • Regulate cerebral blood flow • Form part of the blood–brain barrier || TIP: IRONY: the same astrocytes that protect the brain can give rise to ASTROCYTOMAS, a common brain tumor.

Blood–brain barrier — what is it made of?

The brain's primary security system: astrocytes plus endothelial cells with tight junctions lining the blood vessels. It filters out potentially harmful substances. — It works so well that even the body's own immune cells are blocked from entering brain tissue. || TIP: THIS IS WHY PARKINSON'S CAN'T BE TREATED WITH DOPAMINE — dopamine can't cross the barrier. L-DOPA can.

Microglia — what do they do?

Smaller glial cells — the brain's first-responder / cleanup crew. They patrol for dead cells and debris and monitor the nervous system's microenvironment for threats. || TIP: THE "DOUBLE AGENT" PROBLEM: microglia can turn on the brain's own cells and emit NEUROTOXINS — implicating them in neurodegenerative disease.

Oligodendrocytes vs. Schwann cells

Both build myelin — the difference is location and mechanism: — Oligodendrocyte → myelinates in the CNS (brain + spinal cord). One cell has multiple projections, each forming one myelin segment — so it can myelinate several axons. — Schwann cell → myelinates in the PNS (everywhere else). It wraps its entire cell body around one axon segment. || TIP: The single most-confused pair in this unit. CNS = Oligo. PNS = Schwann.

Radial glia — what are they and when do they exist?

Found only in early life / development. — They form paths and scaffolds that baby cells migrate along in order to develop into mature neurons and reach their correct destinations. || TIP: The one glial type that's DEVELOPMENTAL rather than lifelong — appeared on the exam review slide alongside the other four.

Glia-to-neuron ratio — what did isotropic fractionation reveal?

Old belief: glia outnumber neurons 10:1 (85% of brain cells). New finding: the totals are roughly EQUAL — but the ratio varies wildly by structure: • Thalamus: ~17 glia per neuron • Cerebellum: ~1 glia per 25 neurons || TIP: SECOND SURPRISE: the cerebral cortex holds only ~19% of the brain's neurons. The CEREBELLUM (motor coordination) holds up to 80%.

Resting membrane potential — value and meaning

About −70 mV, with the inside negative relative to the outside. (Textbook range: −50 to −80 mV.) — It exists because ions are unequally distributed across the membrane, and the cell spends energy to keep them that way. || TIP: PURPOSE: a negative resting potential keeps the neuron "relaxed but poised" — ready to fire strongly and fast the instant a stimulus arrives.

Why is the inside of the neuron negative at rest?

NOT because there are extra negative particles inside — because there are FEWER POSITIVE particles inside than outside. — Less positivity inside = negative relative to outside. — Contributing factor: large negatively charged proteins are trapped inside (too big to cross the membrane). || TIP: This is the counterintuitive point Dr. Clabough stressed. Expect it on the exam.

Where is each ion concentrated at rest? (Na⁺, K⁺, Cl⁻, proteins)

• Sodium (Na⁺), positive → concentrated OUTSIDE. Not free-moving. • Potassium (K⁺), positive → concentrated INSIDE. Not free-moving. • Chloride (Cl⁻), negative → outside; FREELY MOVING (can cross without active processes). • Large proteins, mostly negative → trapped INSIDE. || TIP: Na⁺ and K⁺ require ACTIVE processes to cross. Chloride does not — that's why Nernst works so well for it.

Sodium–potassium pump — what does it do and why does it matter?

Pumps 3 Na⁺ OUT for every 2 K⁺ IN, powered by ATP (a phosphate breaks off, releasing energy; ATP → ADP). • Net effect: more positive charge leaves than enters → the interior stays negative • Maintains the gradient: Na⁺ high outside, K⁺ high inside • Restores balance after every action potential — "always working, cleaning up the mess" || TIP: ENERGY COST: ~40% of a neuron's metabolic resources run these pumps. The brain is ~3 lbs but uses ~20% of body energy — mostly this.

Selectively permeable membrane — what does it mean?

The membrane controls the passage of molecules and ions using channels or pores — some things pass, some don't. • Small ions (like Na⁺) can pass through the small openings • Large molecules (proteins) are stuck — they can never leave the axon || TIP: WATCH THE TRAP: it lets SMALL things through and blocks BIG ones — not the reverse.

Phospholipid bilayer

The cell membrane (also called the plasma or axon membrane). Two layers of phospholipids: • Hydrophilic phosphate heads — water-attracting, facing out • Hydrophobic tails — water-avoiding, pointing inward Channels and pumps are embedded proteins that form tubes/pores through it.

Chemical vs. electrical gradient

Two forces act on every ion at once: — Chemical (concentration) gradient — particles diffuse from high to low concentration, seeking even distribution. (Perfume spreading across a room; Kool-Aid powder in water.) — Electrical gradient — opposites attract, like charges repel. (A battery drives current until charges equalize.) || TIP: The resting state is the compromise where both forces are balanced as evenly as possible.

Hodgkin & Huxley's four experiments — what did each show?

1. Both electrodes OUTSIDE the axon → no difference (0). A control proving the equipment works. — 2. One electrode INSIDE, one outside → −70 mV. The resting potential — first demonstration that the inside is negative. — 3 & 4. Same setup plus stimulation → voltage shoots positive, drops below −70, then settles back at −70. That's the action potential. || TIP: Experiment 3 is when the stimulated squid axon fired its escape reflex, flew off the table, and smashed the equipment. #4 was the redo.

Why did Hodgkin & Huxley use a squid? What three tools did they need?

Why the squid: its giant axon (~1 mm) drives a jet-propulsion escape reflex. It's wide enough to fit electrodes in and around, and it's unmyelinated (myelin blocks recording). Invertebrates speed signals with diameter instead of myelin. — The three tools: • Two electrodes — you need two points to measure any electrical difference • An amplifier — the signal is tiny • An oscilloscope — the readout (up = positive, down = negative) || TIP: Axon diameter is PROPORTIONAL to conduction velocity. Bigger axon = faster signal.

Nernst equation — form and what it predicts

V = ±60 · log(ion outside / ion inside) • V = voltage • ±60 log = the constant (sign depends on the ion's charge) • The ratio = concentration outside over concentration inside It predicts the voltage across the membrane for ONE ion at a time, if that ion were freely moving. || TIP: You can predict the voltage anywhere if you know the concentrations on both sides.

Nernst predictions for Cl⁻, Na⁺, and K⁺ — and why they matter

• Cl⁻ ≈ −69 mV — right about the resting membrane potential. Chloride moves fairly freely, which supports the equation. • Na⁺ ≈ +57 mV — very close to the action potential SPIKE. That's where sodium is "happy." • K⁺ ≈ −78 mV — very close to the hyperpolarization VALLEY. || TIP: THE PAYOFF: the Nernst equation predicts the SHAPE of the action potential. The peak and the dip are the points where Na⁺ and K⁺ each briefly move freely.

If Nernst predicts −78 for K⁺ and +57 for Na⁺, why is resting potential −70?

Because sodium and potassium are NOT freely moving. — The sodium–potassium pump is constantly redistributing them (3 Na⁺ out, 2 K⁺ in), holding them out of equilibrium. — −70 mV is the compromise the cell actually settles at — closest to K⁺, since the resting membrane is most permeable to potassium.

What are the 3 variables you can change in the Nernst equation?

• Voltage • Concentration of the ion INSIDE the cell • Concentration of the ion OUTSIDE the cell Researchers tested (and tried to disprove) the equation by manipulating these — using electrodes to hold voltage steady, or bathing a neuron in extracellular fluid with a set ion concentration.

Threshold — what value, and what happens there?

About −55 mV. — The membrane must depolarize from its resting −70 mV up to threshold to trigger an action potential. Reach it → the neuron fires. Fall short → nothing happens. || TIP: THE KEY NUMBERS: rest −70 · threshold −55 · peak ~+40 (Nernst: +57) · hyperpolarization dip ~−78.

Voltage-gated channel — how does it work?

The pore is normally blocked/closed. When the membrane potential reaches threshold, the voltage causes the channel proteins to undergo a conformational change — they physically shift shape, creating space — and the pore opens. — They are ion-specific: a sodium channel passes only Na⁺, a potassium channel only K⁺. || TIP: Different from the always-on Na⁺/K⁺ pump, and different from LIGAND-gated channels (opened by a molecule, not voltage).

What causes DEPOLARIZATION?

Voltage-gated sodium channels open → Na⁺ rushes IN (sodium influx). — Both gradients push sodium inward: the chemical gradient (more Na⁺ outside) and the electrical gradient (inside is negative, attracting positive ions). — All that positive charge drives the inside voltage up, toward the Nernst prediction for free sodium (~+57 mV). || TIP: "Depolarization" = becoming LESS polar, moving closer to zero.

What causes REPOLARIZATION?

Voltage-gated potassium channels open (they need a higher voltage than sodium channels, so they open later) → K⁺ rushes OUT (potassium efflux). — Potassium has been stuck inside and follows its concentration gradient out. The cell loses positivity, so the inside becomes negative again. — Meanwhile sodium channels shut, so no more Na⁺ enters.

Why does HYPERPOLARIZATION occur, and how is it corrected?

The potassium channels are slow to close — potassium keeps leaving even after the cell returns to −70, so the voltage overshoots below resting potential (toward K⁺'s Nernst value of ~−78 mV). — Correction: the channels finally shut, and the sodium–potassium pump — always working — redistributes the ions and brings the cell back to −70 mV. || TIP: The overshoot happens BECAUSE freely-moving potassium would settle even more negative than resting potential.

Refractory period — what is it and why does it matter?

The stretch during and after hyperpolarization when the cell is busy putting ions back where they belong. — Another stimulus cannot trigger an action potential during this time. • Absolute refractory — no amount of stimulation works • Relative refractory — a stronger-than-usual stimulus is required || TIP: TWO CONSEQUENCES: (1) it caps a neuron's max firing rate (~200/second) and (2) it's WHY the action potential travels in only one direction.

All-or-none law

Every action potential in a neuron is identical — same size, same shape, same duration (~2 milliseconds), same speed down the axon. — There is no such thing as a bigger, taller, or longer action potential. It fires fully or not at all. || TIP: SO HOW DOES INTENSITY GET ENCODED? You get MORE action potentials, or more cells firing — not bigger ones. Discovered by Edgar Adrian.

Graded potential — three properties

How an electrical disturbance spreads through anything (a wall, a wet noodle, a wire, a neuron): • Graded / incremental — can be any size; a little current gives a little change • Decremental — it dissipates and diminishes as it travels, so it doesn't go far • Very fast — close to the speed of light • Spreads in all directions from the source || TIP: Undersea telephone cables needed AMPLIFIERS for exactly this reason — the signal decays over distance.

Graded potential vs. action potential — compare

GRADED: any size · decays over distance · very fast (near light speed) · spreads all directions — ACTION: all-or-none · doesn't fade (regenerates) · slow (~100 m/s, ~2 ms) · one direction only — Why the AP is slow: every step requires physical movement — channel proteins changing shape, then thousands of ions physically moving through. || TIP: THE KEY INSIGHT: the neuron uses BOTH. Fast-but-fading graded potentials and slow-but-stable action potentials work together.

Why don't all graded potentials result in an action potential? (exam review question)

Because graded potentials must reach the THRESHOLD (−55 mV) to trigger an action potential. — A graded potential is incremental and decays as it travels. If it arrives at the axon hillock too weak — or started too small — it never crosses threshold, and no action potential fires. || TIP: They are NOT unrelated phenomena, and action potentials are NOT limited to myelinated regions. Watch those distractors.

Propagation — how does the action potential travel down the axon?

Think of the axon as segments (not physically separate). • One segment fires an action potential • That spike creates an electrical disturbance that travels forward as a graded potential • Even though it's decaying, it's still above threshold when it reaches the next segment → opens its sodium channels → a full new action potential is born • Repeat down the axon || TIP: It's called PROPAGATION because the signal is REGENERATED ("reborn") at each step — like cutting a plant and repotting it — not just passed along.

If graded potentials spread in all directions, why does the AP only go ONE way?

The refractory period. — The action potential is generated at the axon hillock (loaded with pumps, very sensitive). As it travels, the hyperpolarized refractory zone trails right behind it. — That trailing segment can't fire again — it's still re-establishing resting potential, and the dip is lower than normal. So the signal can only move forward, into the fresh segment ahead.

Saltatory conduction — describe the alternating pattern

Myelin wraps the axon so tightly that ions can't cross — so the action-potential machinery can't operate underneath it. — At a NODE OF RANVIER = ACTION POTENTIAL (slow). Under the MYELIN = GRADED POTENTIAL (fast). → node → myelin → node → myelin… — The impulse effectively jumps from node to node (Latin saltare = "to jump"). Voltage-gated Na⁺ channels cluster at the nodes. || TIP: Like tossing a ball to every fifth person instead of passing it one by one.

If myelin speeds signals up, why isn't everything myelinated?

It's a resource trade-off: • Myelin SAVES neuronal resources — a myelinated stretch doesn't need all those Na⁺ channels, K⁺ channels, and pumps (they're concentrated only at the nodes) • But myelin COSTS body resources — you have to build the glial cells that produce it The body constantly balances which signals matter enough to pay for speed. || TIP: WATCH THE TRAP: myelin is NOT easy or cheap to produce. That's exactly why it's selective.

Myelination and development

Myelination is one of the LAST steps in brain development — axons can't be myelinated until neurons have reached their destinations and axons have found their targets. • White matter appears in the third trimester (you can gauge fetal age by how much is present) • Continues through the third decade of life (mid-20s) • Tracks ability: as arm nerves myelinate, kids gain fine independent control. Hippocampal myelination → memory increases • Practice increases myelin; once myelinated, it generally stays for life

Two ways the body speeds up a signal

• Axon diameter — bigger cross-section = faster conduction. (The squid's solution; invertebrates have little/no myelin.) • Myelin — insulation enabling saltatory conduction. (The vertebrate solution.) || TIP: Why speed matters for INTEGRATION: signals must arrive at the same TIME to summate. Demyelination breaks the timing window even if the signal still arrives.

Multiple sclerosis — what goes wrong?

A demyelinating disease: the myelin-producing cells die, leaving exposed axons — particularly on neurons traveling long distances to peripheral parts of the body. — The impulse is weakened — "like an exposed portion of an electrical cord that grounds out" — producing both sensory and motor impairments. || TIP: Once myelin is lost it typically CANNOT be regenerated, especially in the CNS. The PNS can sometimes regenerate along the Schwann-cell trail.

List the events that occur when depolarization arrives at the axon terminal

• The action potential arrives → the terminal membrane goes very positive • This opens voltage-gated CALCIUM (Ca²⁺) channels — the third ion of the course • Ca²⁺ influx — calcium is higher outside, so it flows in • Calcium triggers vesicles to dock at the membrane • Vesicles fuse and release their neurotransmitter = EXOCYTOSIS • Neurotransmitter diffuses across the synaptic cleft (~10–20 nm) • It binds receptors on the postsynaptic cell

Synapse naming — axodendritic and the rest

Named from → to: • Axodendritic — axon → dendrite (the model case) • Axosomatic — axon → cell body • Axoaxonic — axon → axon • Dendrodendritic — dendrite → dendrite || TIP: On an electron micrograph, the synapse is the DARK SPOT at the tip of a dendritic spine — dark because of all the synaptic machinery packed there.

Ligand-gated channel — how is it different from a voltage-gated channel?

A ligand is just a fancy word for a molecule. — Ligand-gated: a MOLECULE (the neurotransmitter) binds and opens the channel. No voltage change needed. Found on the postsynaptic membrane. — Voltage-gated: a change in VOLTAGE opens the channel. Drives the action potential. || TIP: Both are ion-specific — a ligand-gated sodium channel passes only sodium.

Neurotransmitter specificity — explain it

Receptors work like a LOCK AND KEY. — A neurotransmitter can only act on the receptor shaped for it — it must fit correctly in order to open the channel. A circle-shaped ligand won't fit a V-shaped receptor. — So the same released neurotransmitter only affects cells carrying its specific receptor.

Quantal release — why can't a terminal release 250 molecules?

Each vesicle is like an envelope holding a fixed number of neurotransmitter molecules (a quantum). — Release happens one whole vesicle at a time, so the total always comes in INTEGER MULTIPLES of the quantum. — If each vesicle holds 100: you can release 100, 200, 300, 400… but never 250 — that's not a whole number of vesicles. || TIP: Boosting the NUMBER of quanta released is one way to change the effect on the postsynaptic neuron.

Dale's Law

Neurons are named for what they release (serotonergic, dopaminergic, etc.). — A neuron can release more than one neurotransmitter — but when they're packaged together, every vesicle has the SAME composition. — If one vesicle holds a 40:60 ratio of two transmitters, every vesicle from that neuron holds that same 40:60 ratio. The vesicles are homogeneous.

Name 2 ways to remove neurotransmitter from the synapse

If neurotransmitter lingers, the receptors keep re-activating and cause a mess. Two mechanisms: • REUPTAKE — transporters on the presynaptic cell suck the neurotransmitter back up (endocytosis) and repackage it into vesicles for reuse. Saves the cell from making so much. • ENZYMATIC BREAKDOWN — an enzyme in the cleft destroys it. Each enzyme is specific: acetylcholinesterase breaks down acetylcholine. || TIP: Both are drug targets — cocaine and SSRIs block REUPTAKE; physostigmine blocks BREAKDOWN.

Describe the 3 possible membrane potential changes in a postsynaptic neuron

• Depolarization — Na⁺ comes IN → inside more positive → closer to threshold → an EPSP • Hyperpolarization — K⁺ goes OUT (or Cl⁻ comes in) → inside more negative → further from threshold → an IPSP • Flat / no net change — sodium rushing in and potassium rushing out at the same time cancel each other, so the net result is flat || TIP: The PREsynaptic side is binary (all-or-none). The POSTsynaptic side has options — that's where drugs work.

EPSP vs. IPSP

EPSP — Excitatory PostSynaptic Potential A depolarization. Brings the neuron closer to threshold, more likely to fire. Caused by positive ions (Na⁺) flowing IN. — IPSP — Inhibitory PostSynaptic Potential A hyperpolarization. Pushes the neuron further from threshold, harder to fire. Caused by positive ions (K⁺) flowing OUT, or negative ions (Cl⁻) flowing IN. || TIP: Glutamate → EPSP. GABA → IPSP.

Ionotropic receptor — how does it work?

The fast, direct one. — The neurotransmitter (ligand) binds → a channel opens directly in the membrane → ions (Na⁺, K⁺, Cl⁻) flow through → produces an EPSP or IPSP → the cell becomes more or less likely to fire. — Always SHORT-LASTING. || TIP: Ionotropic channels can let Na⁺ IN (excitatory), Cl⁻ IN, or K⁺ OUT (both inhibitory). Not limited to one ion or direction.

Metabotropic receptor — how does it work?

The slow, indirect one. Also called a second-messenger coupled receptor (the well-studied family is G-protein coupled receptors). — The ligand binds → releases a SECOND MESSENGER inside the postsynaptic neuron. That second messenger can: • Enter the nucleus and turn on gene transcription • Modulate neighboring ion channels • Activate or deactivate enzymes • Change the cell's resting membrane potential LONGER-LASTING — can produce long-term changes.

Ionotropic vs. metabotropic — which lasts longer?

METABOTROPIC effects last LONGER. Both are activated quickly, but metabotropic effects operate on a much slower time scale. — Ionotropic = direct channel opening → fast on, fast off, short Metabotropic = second-messenger cascade → slower, longer-lasting, can even alter gene expression || TIP: COMMON TRAP: "ionotropic effects last longer" is FALSE. It's the reverse.

Can second messengers change a cell's resting membrane potential?

YES. — Second messengers act inside the cell and can indirectly open or close ion channels. Changing how ions move across the membrane changes the charge difference across it — i.e. the resting membrane potential. — So a metabotropic receptor can make a cell more or less likely to fire without a neurotransmitter ever directly touching a channel. || TIP: About 32 different things can happen in the postsynaptic cell — an enormous range from one all-or-none input.

Acetylcholine — where was it discovered and what does it do?

The first neurotransmitter ever discovered, found at the NEUROMUSCULAR JUNCTION — the synapse where a motor neuron meets a muscle fiber. The muscle is the postsynaptic cell. — ACh binds receptors on the muscle → the muscle contracts. It's how we move. — Otto Loewi's frog-heart experiment identified it. || TIP: ACh has TWO receptor types: NICOTINIC (ionotropic) and MUSCARINIC (metabotropic).

Monoamines — name them

Chemically related — you have to make one before you can get the next (a synthesis sequence). • Serotonin (5-HT) • Catecholamines: Dopamine → Norepinephrine → Epinephrine || TIP: These are exactly the transmitters STIMULANTS target — cocaine and amphetamine block reuptake of 5-HT, DA, and NE.

Amino acid neurotransmitters — glutamate and GABA

Glutamate — the most common EXCITATORY neurotransmitter. Opens channels letting Na⁺ in → depolarization → EPSP. — GABA (γ-aminobutyric acid) — the most common INHIBITORY neurotransmitter. Lets K⁺ out (or Cl⁻ in) → hyperpolarization → IPSP. — Both work on ionotropic AND metabotropic receptors. || TIP: Ionotropic vs. metabotropic is a property of the RECEPTOR, not the transmitter.

Peptides and "others"

Peptides — made of amino-acid chains. Examples: endorphins (endogenous morphines) and substance P. — Others — gases and purines. || TIP: Endorphins are why opioid receptors exist in the first place: if we have receptors for a drug, we must have a natural version of it.

Temporal summation — explain it

Summation in TIME, from ONE presynaptic neuron. — If the same events are spread over seconds you get separate little bumps. But fire them rapidly in succession and the postsynaptic cell doesn't have time to recover to resting potential — so each new EPSP stacks on top of the last and can cross threshold. — Same number of messages, more powerful stimulus. The faster the presynaptic cell fires, the more likely the postsynaptic cell responds. || TIP: Capped by the REFRACTORY PERIOD — one neuron can't fire more than ~200 times/second.

Spatial summation — explain it

Summation in SPACE, from MULTIPLE presynaptic neurons. — If two or more different cells deliver input to the same postsynaptic cell at the same time, their EPSPs jump on top of each other → closer to threshold → more likely to fire. — Key advantage: it is NOT limited by the refractory period. Many cells can fire simultaneously even though a single cell is capped at ~200 Hz — so this gives the system far more power.

Temporal vs. spatial summation — same and different

SAME: • Both add EPSPs together to push the cell toward threshold • Both depend on inputs arriving close together in time • Both are cumulative/additive and determine whether an AP is generated DIFFERENT: • Temporal = ONE neuron firing repeatedly — timing/frequency from a single source; refractory-capped • Spatial = MULTIPLE neurons firing at once — spatial arrangement of many sources; not refractory-capped

If an IPSP and an EPSP occur simultaneously on the same dendrite, what does the recording show?

A FLAT LINE — they cancel each other out. — EPSPs and IPSPs sum algebraically. If a glutamate EPSP and a GABA IPSP arrive at exactly the same time, the recording shows no net change at all — as if nothing happened. — The cell is effectively turned off. || TIP: If they arrive at DIFFERENT times you see the bumps separately — one up, one down.

Hierarchical synapses — why does the LOCATION of a synapse matter?

Not all synapses are equal — some are strong, some weak. The deciding factor is DISTANCE TO THE AXON HILLOCK. — The signal travels down the dendrite as a graded potential, which is decremental — it diminishes as it goes. • Far from the cell body: a tiny depolarization out on a distal dendrite won't have enough current left to reach the hillock. It barely matters. • Close to the cell body: the same input arrives intact, the hair-trigger hillock reaches threshold, and an AP fires.

Can 3 EPSPs be outvoted by 1 IPSP? (the counterintuitive case)

YES — if the IPSP is closer to the axon hillock. — Three excitatory synapses far out on a dendrite decay on the way down. One inhibitory synapse near the hillock arrives at full strength. They can balance out, and the cell moves neither up nor down. — You must weigh location, not just count inputs. || TIP: EXAM REVIEW VERSION: if synapse A (3 EPSPs) and synapse B (1 IPSP) were EQUIDISTANT, the EPSPs should win and fire the cell — so "equidistant" is NOT a reason no AP occurred.

Why is the firing of a postsynaptic neuron "probabilistic"?

It is not "an action potential comes in → the next cell fires." The soma and axon hillock must integrate everything: • Time — temporal summation • Space — spatial summation • Sign — EPSP vs. IPSP • Location — hierarchical synapses • Receptor type — ionotropic vs. metabotropic A single neuron may have 10³–10⁵ synapses. The cell uses the entire dendrite, not a single input. || TIP: This is why demyelination is so damaging — if a signal arrives LATE it misses the coincidence window, and summation fails.

Myasthenia gravis — cause and consequences

Cause: an autoimmune disorder — the immune system misidentifies the body's own tissue as an invader and attacks postsynaptic ACETYLCHOLINE RECEPTORS at the neuromuscular junction. — Consequences: ACh can't bind → the muscle can't contract → progressive weakness, muscles go limp. Eventually affects the diaphragm, so patients may need a ventilator. No cure. — ~14 per 100,000 people. || TIP: A tiny change at ONE synapse produces a fatal, whole-body outcome. It's CHOLINERGIC — and the only one of the three diseases that is NOT a basal ganglia disorder.

Parkinson's disease — what causes the symptoms?

Preferential death of DOPAMINERGIC neurons in the SUBSTANTIA NIGRA ("black substance" — the cells look black in an unstained dissection). It's part of the basal ganglia, which controls movement. — Two hallmark symptoms: • Inability to move — patients feel "frozen in their own bodies"; a shuffling gait, poor leg articulation, torso doesn't move • RESTING tremor — shaking at rest that goes AWAY once voluntary movement begins || TIP: An INTENTION tremor (during movement) is NOT Parkinson's. And a tremor alone doesn't mean Parkinson's — plenty are benign.

Why is Parkinson's treated with L-DOPA instead of dopamine?

Dopamine cannot cross the blood–brain barrier (built by astrocytes). Given as a drug it would stay in the peripheral nervous system and never reach the brain — useless. — L-DOPA is the PRECURSOR to dopamine and CAN cross the barrier. Once inside, the body manufactures dopamine from it. — Awakenings — patients unable to move were catching balls within ~20 minutes. || TIP: BUT: the substantia nigra keeps dying, patients build TOLERANCE (higher doses), and side effects escalate. There is no cure.

Huntington's disease — explain it

Death of medium spiny neurons — inhibitory neurons that use GABA — in the STRIATUM (caudate + putamen), a different part of the basal ganglia. — Symptom: CHOREA — dance-like, uncontrollable movements. Starts in arms and head, progresses to writhing movements. Depression and cognitive decline may appear before the movement symptoms. — Genetics: autosomal dominant — one mutant huntingtin gene = you get the disease. 50/50 chance of passing it on. Symptoms start at midlife, often after reproductive decisions are made. No cure. (Woody Guthrie.)

Parkinson's vs. Huntington's — the key contrast

They are opposites, and the logic maps directly from synapse to symptom: — PARKINSON'S — lose DOPAMINE (excitatory input) in the substantia nigra → TOO LITTLE movement, can't initiate. — HUNTINGTON'S — lose GABA (inhibitory input) in the striatum → TOO MUCH movement, can't stop. || TIP: THE RULE: lose EXCITATION → can't move. Lose INHIBITION → can't stop moving.

Epilepsy — what is happening in the brain?

Synchronized overexcitability. Normal brain activity is ASYNCHRONOUS (different regions doing different things). During a seizure it becomes SYNCHRONOUS — populations of neurons firing together. • Partial seizures — start in a localized area • Generalized seizures — span both hemispheres Aura = the warning experience before a seizure; differs person to person. Theory: the seizure starts where the aura is localized. || TIP: STADIUM ANALOGY: thousands of separate conversations = normal. Everyone doing "the wave" together = a seizure.