Part I · Chapter 2 · Lectures 2 & 4

Neurons, spikes & synapses

The cells of the nervous system, how an all-or-none spike can still carry "how much", how synapses pass the signal on, how drugs for Parkinson's and depression hijack that step, and the three ways synapses change with experience.

1. A multi-scale, hierarchical system

"How does the brain work?" is unanswerable as stated, because the answer depends on the scale you're looking at. The lecture's ladder:

Four scales of the nervous system
1 · Cell 2 · Circuit 3 · Cortical column 4 · Brain → increasing scale → (the brain level is itself divided four ways: Ch. 3)

Some numbers the lecture gives: ~100 billion neurons, ~100 trillion synaptic connections, ~5,000 connections per neuron.

2. The four main cell types

CellJobWhere
NeuronCarries information. Soma = cell body; dendrites = receiving side; axon = transmitting side.Everywhere
Schwann cellMyelination — wraps axons in a fatty insulating layer.Peripheral NS
OligodendrocyteMyelination.Central NS (brain + spinal cord)
AstrocyteMaintains the blood–brain barrier and modulates neural activity.CNS
Common mistake Swapping Schwann cells and oligodendrocytes. They do the same job (myelin) in different places. One hook: Schwann = Side (peripheral); Oligo = the Organ in the middle (CNS).

Four shapes of neuron

Shape follows job. Count the processes leaving the cell body:

Neuron morphologies (dendrites thin, axon thick)
MultipolarBipolarUnipolarAnaxonic 1 axon, many dendrites · integration1 axon, 1 dendrite · special senses 1 process → splits in 2 · long-distance sensoryno distinct axon · local processing
What to notice: the purpose column is what gets tested. Many dendrites = many inputs = integration. No axon = can't send far = local processing. The lecture's named examples — pyramidal and Purkinje neurons (Purkinje live in the cerebellum, drawn by Ramón y Cajal) — are both multipolar.

3. The action potential

Neurons talk with electricity. The problem they have to solve: send a signal down an axon that may be a metre long without it fading. The solution is a pulse that regenerates itself as it travels and is always the same size.

Definition Action potential — a brief, all-or-none change in a neuron's voltage that travels along the axon to transmit information. Refractory period — the time during/after a spike when the neuron is less likely to fire again.

The four steps (study guide):

  1. Initial stimulus pushes the voltage up to threshold.
  2. Depolarization — Na⁺ channels open, Na⁺ rushes in, voltage shoots up.
  3. Repolarization — K⁺ channels open, K⁺ rushes out, voltage falls.
  4. Hyperpolarization — some K⁺ channels stay open, so voltage undershoots rest before recovering.
Analogy (from lecture) Friend annoys you (threshold reached → Na⁺ channels open) → you get salty (Na⁺ — sodium — rushes IN) → you get really worked up (depolarization) → you calm down (K⁺ channels open, K⁺ rushes OUT) → back to rest. Where it leaks: you can be a little annoyed; a neuron can't be "a little" spiking.

Now the puzzle the lecture poses and leaves for you: if action potentials are all-or-none, how can neurons signal different amounts of information? Drag the stimulus slider.

Spikes are all-or-none — the rate carries the "how much"
What to notice: below threshold, nothing happens at all — no small spikes. Above it, every spike is the same height; a stronger stimulus only makes them come more often. Push the stimulus to the top and the rate stops growing: the refractory period caps how fast the cell can fire (raise the refractory slider and watch the cap drop). Simplified integrate-and-fire model; voltages are textbook-typical, not from the slides.
Key idea Frequency coding — neurons represent different amounts of information by how frequently they fire action potentials, not by how big the spikes are. That's the answer to the lecture's puzzle.

4. Synapses: passing the signal on

A synapse is the gap between neurons. Two kinds:

Electrical synapseChemical synapse
SpeedFaster — current flows directlySlower — chemicals must be released and diffuse
FlexibilityLess flexibleMore flexible — can be tuned up or down
ExampleIn the eye & heartMost of the brain
Machinery—Neurotransmitters, receptors, reuptake

Neurotransmitters in the lecture: glutamate (excitatory), GABA (inhibitory), dopamine (can be both, depending on the receptor). After release, the transmitter is cleared from the gap by reuptake (pumped back into the sending neuron) or broken down by enzymes. Those clearance steps are exactly where drugs act.

A chemical synapse — try the drugs

The drugs, mechanism by mechanism

Parkinson's disease drugs PD = loss of dopamine neurons, so less dopamine reaches receptors. Three strategies:
  • Dopamine agonists — mimic dopamine and bind its receptors.
  • Amantadine — limits reuptake, so dopamine stays in the gap longer.
  • COMT / MAO-B inhibitors — limit the enzymes that break dopamine down.
(L-dopa, which adds dopamine to the system, comes in Ch. 7.)
Depression drugs (Lecture 4) Depression involves changes across systems for mood, reward, motivation, stress and cognition. Serotonin is a neuromodulator that influences many of them.
  • SSRIs (Selective Serotonin Reuptake Inhibitors) block serotonin reuptake → more serotonin remains in the synapse.
  • Other antidepressants: less serotonin breakdown, or more serotonin release.
Intuition Every one of these drugs does the same thing from a different angle: raise the effective amount of transmitter acting on receptors. Make more, release more, clear less (reuptake), break down less (enzymes), or fake it (agonist). If you understand the life cycle of a transmitter — release → bind → clear — you can derive any drug question.
Try itFix the broken synapse (workbook exercise)

A presynaptic neuron fires normally. It releases plenty of glutamate. The postsynaptic neuron never fires. A test shows its glutamate receptors are intact but the cleft is flooded with an enzyme that destroys glutamate within microseconds. Diagnose and fix.

Step 1 — Where does transmission fail?

Walk the chain: spike arrives ✓ → release ✓ → transmitter crosses gap ✗ (destroyed before it binds) → receptors ✓. The break is in the cleft.

Step 2 — What would restore it?

Inhibit the enzyme (the COMT/MAO-B strategy, applied to glutamate), or bypass it with an agonist that the enzyme can't degrade.

Answer & the takeaway

Enzyme inhibitor → glutamate survives long enough to bind → postsynaptic neuron reaches threshold. The skill being tested: locate the failure in release → bind → clear, then pick the drug strategy that acts at that step. Blocking reuptake wouldn't help here — the transmitter never lived long enough to be taken back up.

5. Plasticity: three ways synapses change

Definition Plasticity — the nervous system's ability to change its structure or function in response to experience.
MechanismWhat physically changesLecture example
1. Long-term potentiation / depression (LTP / LTD)Adding or removing channels; increasing or decreasing transmitter release. Same synapse, stronger or weaker.Potentiation = studying for FoBB. Depression = forgetting FoBB. Habituation involves LTD.
2. Dendritic growth vs retractionNew synapses form (~4 days to form a synapse, seen with electron microscopy); or dendrites are pruned.Cat: pruning from prenatal ~8 days to 1 year. Neurotypical vs aberrant pruning.
3. Astrocyte regulationClassically just the blood–brain barrier; recently shown to also regulate neural activity.—
Definition Habituation — a basic form of learning in which an organism's response to a repeated, benign stimulus gradually decreases over time. Mechanism: long-term depression of the synapses carrying it. (You stop noticing your clothes on your skin.)
Common mistake "Depression" in LTD means weakened synapse, nothing to do with the mood disorder or SSRIs. And habituation is LTD, not LTP — the response goes down.

6. The five general principles

  1. The nervous system is a multiscale, hierarchical structure.
  2. It is incredibly diverse (cell types, neuron shapes).
  3. It is highly interconnected (~5,000 connections per neuron).
  4. It is plastic.
  5. It is complicated ☺

7. Check yourself

A stronger touch on your skin is signalled to the brain mainly by…
Why: Frequency coding. Spikes are all-or-none, so they can't get bigger — the tempting first option is exactly the misconception the lecture's question targets.
During which phase are K⁺ channels open while voltage drops below resting level?
Why: Repolarization also involves K⁺ leaving, but it brings the voltage back toward rest. The undershoot below rest — because some K⁺ channels are still open — is hyperpolarization. Depolarization is the Na⁺ phase.
SSRIs and amantadine have what in common?
Why: SSRIs block serotonin reuptake (depression); amantadine limits dopamine reuptake (PD). Different transmitter, different disease, same mechanism. COMT/MAO-B inhibitors are the enzyme ones; agonists are the mimics.
Myelin in the spinal cord is made by…
Why: The spinal cord is CNS. Easy to miss because people think "CNS = brain". Schwann cells are peripheral.
You move next to a train line. After a month you no longer notice trains. This is ___, caused by ___.
Why: Repeated, benign stimulus + decreasing response = habituation, implemented by LTD. Change blindness is about failing to notice a change, not tuning out a constant repetition.