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Neuroscience / 86 billion cells, talking

Brain, mind, cognition — a clinical tour of the most complex object known to science.

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Brain, mind, cognition — a clinical tour of the most complex object known to science. Key sections include: NEUROSCIENCE 86 billion cells, talking.; The neuron — an electrical wire that thinks.; The action potential — a 1 ms electrical spike.; Synapses — chemical conversation, ~100 trillion of them.; Anatomy — one brain, many regions, two halves.; Sensory & motor — the brain’s I/O bus.; Memory — how the brain holds onto time.; Broca, Wernicke, and what aphasia teaches us.; Cajal vs. Golgi — the 1906 Nobel.; The modern toolkit..

Key sections

01NEUROSCIENCE 86 billion cells, talking.
02The neuron — an electrical wire that thinks.
03The action potential — a 1 ms electrical spike.
04Synapses — chemical conversation, ~100 trillion of them.
05Anatomy — one brain, many regions, two halves.
06Sensory & motor — the brain’s I/O bus.
07Memory — how the brain holds onto time.
08Broca, Wernicke, and what aphasia teaches us.
09Cajal vs. Golgi — the 1906 Nobel.
10The modern toolkit.
11What we still don’t know.
12Brain disorders — where the work matters.
13Where to go next.

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Slide outline

01NEUROSCIENCE 86 billion cells, talking.
02The neuron — an electrical wire that thinks.
03The action potential — a 1 ms electrical spike.
04Synapses — chemical conversation, ~100 trillion of them.
05Anatomy — one brain, many regions, two halves.
06Sensory & motor — the brain’s I/O bus.
07Memory — how the brain holds onto time.
08Broca, Wernicke, and what aphasia teaches us.
09Cajal vs. Golgi — the 1906 Nobel.
10The modern toolkit.
11What we still don’t know.
12Brain disorders — where the work matters.
13Where to go next.

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Slide 01

NEUROSCIENCE 86 billion cells, talking.

Neuroscience · Lecture series
Brain, mind, cognition — a clinical tour of the most complex object known to science.
13 slides
Topic The brain, the cell, the network
Reading time ~12 min

Slide 02

The neuron — an electrical wire that thinks.

02 · The cell
~86 billion neurons in the human brain[1], each with thousands of inputs. Specialized for one job: receive a signal, decide, transmit.
Fig 2.1 · A typical neuron, schematic
Dendrites — branched receivers, sum thousands of inputs.
Soma — cell body; if input crosses threshold, fires.
Axon — wire-like output, can stretch over a meter.
Synapse — the gap where one neuron talks to the next.
Glia — support cells; roughly 1:1 with neurons[2].
[1] Azevedo et al., J Comp Neurol (2009) — isotropic fractionator count.
[2] von Bartheld et al. (2016) revised the old "10:1 glia" myth.

Slide 03

The action potential — a 1 ms electrical spike.

03 · The signal
When inputs push the membrane past about −55 mV, voltage-gated Na⁺ channels snap open. The cell depolarizes, then K⁺ channels reset it. Repeat down the axon at up to ~100 m/s in myelinated fibres[1].
Fig 3.1 · Membrane voltage during a single spike (~1 ms)
Resting potential ~−70 mV, maintained by Na⁺/K⁺ pump.
Threshold ~−55 mV — an all-or-nothing decision.
Peak ~+40 mV — Na⁺ rushes in.
Refractory period — can’t fire again immediately.
Saltatory conduction — signal jumps between Nodes of Ranvier in myelinated axons[2].
[1] Hodgkin & Huxley, J Physiol (1952) — squid giant axon model. 1963 Nobel.
[2] Conduction velocity scales with axon diameter and myelination.

Slide 04

Synapses — chemical conversation, ~100 trillion of them.

04 · The handshake
An action potential reaches the terminal, calcium floods in, vesicles dump neurotransmitter into a 20 nm gap. The next cell’s receptors decide what to do. The whole thing takes about half a millisecond.[1]
~1014
Synapses
Roughly 100 trillion connections in an adult brain — an order of magnitude more than there are stars in our galaxy.
~50
Neurotransmitters
Glutamate (excite), GABA (inhibit), dopamine, serotonin, acetylcholine, norepinephrine, and many peptides.
LTP
The cellular basis of learning
Long-term potentiation: repeatedly co-active synapses get stronger[2]. Hebb’s rule — "neurons that fire together, wire together."
0.5 ms
Synaptic delay
Time from arriving spike to postsynaptic response — the rate-limiting step in neural circuits.
[1] Sakmann & Neher, patch-clamp methods — 1991 Nobel.
[2] Bliss & Lømo (1973), hippocampal LTP, Journal of Physiology.

Slide 05

Anatomy — one brain, many regions, two halves.

05 · The map
Fig 5.1 · Lateral view, left hemisphere
Cerebrum — the wrinkled outer layer; thinking, perception, voluntary action.
Cerebellum — "little brain"; balance, motor timing, fine coordination.
Brainstem — breathing, heart rate, the things you can’t turn off.
Four lobes — frontal (planning), parietal (touch/space), temporal (hearing/memory), occipital (vision).
Two hemispheres linked by the corpus callosum; each receives the opposite side of the body.

Slide 06

Sensory & motor — the brain’s I/O bus.

06 · In and out
Cortex is organized as topographic maps: neighbouring neurons code for neighbouring features. Discovered by carefully poking the cortex with electrodes — literally.
Primary visual cortex (V1)
Hubel & Wiesel (1959) found neurons that fire only for edges at a specific orientation[1]. The retinal image is mapped point-for-point onto V1 in the occipital lobe.
Primary motor cortex (M1)
A strip of cortex along the central sulcus where each patch controls a specific muscle group. Stimulate it, the body twitches.
Somatotopy · the homunculus
Penfield’s wartime maps showed lips, hands, and tongue claim disproportionate cortical real estate — sensitivity, not size, sets the scale[2].
Cross-modal plasticity
In congenitally blind people, "visual" cortex is recruited for Braille reading. Maps re-write themselves when the input changes.
[1] Hubel & Wiesel, J Physiol (1959); 1981 Nobel.
[2] Penfield & Boldrey, Brain (1937).

Slide 07

Memory — how the brain holds onto time.

07 · The hippocampus
In 1953, surgeons removed both hippocampi from a young man named Henry Molaison — "Patient H.M." — to stop his seizures. They worked. But H.M. could no longer form new long-term memories.[1]
"Every day is alone in itself. Whatever enjoyment I’ve had, and whatever sorrow I’ve had."
— Henry Molaison, c. 1980
H.M. founded modern memory research. We learned that declarative memory (facts, events) needs the hippocampus, but procedural memory (skills) does not — he could still learn new motor tasks without remembering having practiced them.
Encoding — hippocampus binds together cortical activity into an episode.
Consolidation — over hours to years, memories migrate to neocortex[2].
Sleep replays the day's hippocampal activity at high speed (sharp-wave ripples).
Place cells — O’Keefe (1971); a hippocampal map of where you are. 2014 Nobel.
Forgetting — not a bug; selective decay keeps memory useful.
[1] Scoville & Milner, J Neurol Neurosurg Psychiatry (1957).
[2] Standard model: McClelland, McNaughton & O’Reilly (1995).

Slide 08

Broca, Wernicke, and what aphasia teaches us.

08 · Language
Two 19th-century clinicians, two patients, two distinct deficits — and the first localized account of any cognitive function in the brain.
Broca's area · left frontal
Damage here produces Broca’s aphasia: speech is halting, ungrammatical, effortful — but comprehension is largely intact. The patient knows what they want to say.
"Walk dog. Yes... outside. Hard."
— A typical Broca’s aphasia utterance
Wernicke's area · left temporal
Damage here produces Wernicke’s aphasia: fluent, grammatical, melodic speech — but comprehension is impaired and the words come out as nonsense. Patients are often unaware.
"I called my mother on the television and did not understand the door."
— A typical Wernicke’s aphasia utterance
Modern fMRI shows language is more distributed than the classical model suggested[1] — but Broca’s and Wernicke’s patients are still where every neurology resident starts.
[1] Hagoort, Trends Cogn Sci (2014); Fedorenko et al. on the language network.

Slide 09

Cajal vs. Golgi — the 1906 Nobel.

09 · History
Camillo Golgi invented the silver-nitrate stain that, mysteriously, blackens only a few neurons at random — rendering each one in exquisite detail.[1]
Santiago Ramón y Cajal, a Spanish histologist, used Golgi’s stain to draw thousands of neurons by hand. He concluded that the brain is made of discrete cells, not a continuous web — the neuron doctrine.
They shared the 1906 Nobel Prize. They disagreed bitterly in their acceptance speeches. Cajal turned out to be right.[2]
Pyramidal neuron, after Cajal (1899)
[1] Golgi (1873), la reazione nera.
[2] The reticular vs. neuronal theory debate — resolved by electron microscopy in the 1950s.

Slide 10

The modern toolkit.

10 · Tools
Twenty years ago neuroscience meant electrodes and post-mortem slices. Today we can image, manipulate, and reconstruct circuits at multiple scales simultaneously.
fMRI
Functional MRI tracks blood-oxygen changes (BOLD signal) at ~1 mm resolution — the workhorse of cognitive neuroscience since the 1990s.[1]
Optogenetics
Channelrhodopsins from algae let researchers switch specific neurons on or off with millisecond pulses of blue light.[2] Causation, not just correlation.
Calcium imaging
GCaMP fluoresces when calcium rises during a spike. Two-photon microscopy can record thousands of neurons simultaneously in a behaving mouse.
Connectomics
Serial electron microscopy + deep learning reconstructs every synapse in a tissue volume. Full Drosophila brain mapped in 2024[3]; mouse cortex underway.
[1] Ogawa et al. (1990) discovered BOLD contrast.
[2] Boyden, Deisseroth et al., Nat Neurosci (2005).
[3] FlyWire consortium, Nature (Oct 2024) — ~140k neurons, ~50M synapses.

Slide 11

What we still don’t know.

11 · Frontier
Despite a century of progress, the deepest questions remain genuinely open. These are the problems a young researcher could bet a career on.
Consciousness
Why does any physical process feel like something? The "hard problem"[1]. Leading frameworks: Global Workspace Theory, Integrated Information Theory — neither yet decisive.
YouTube · Consciousness & neuroscience →
The binding problem
Color, shape, motion, and location are processed in separate cortical regions. How are they fused into a single, unified percept of "red car moving left"?
What is a dream?
REM sleep is universal among mammals and birds. Dreams may be memory replay, threat rehearsal, noise — or essential to learning. We still don’t know.
The engram
If memory is stored physically in the brain, where? Recent work (Tonegawa lab) tags and reactivates specific memory traces in mice[2] — but the full code is still cryptic.
[1] Chalmers, J Conscious Stud (1995).
[2] Liu, Ramirez et al., Nature (2012); engram cell tagging in hippocampus.

Slide 12

Brain disorders — where the work matters.

12 · Clinical
Roughly one in three people will be affected by a neurological or psychiatric disorder in their lifetime[1]. The clinic is where neuroscience meets the world.
Aβ
Alzheimer’s disease
Amyloid-β plaques and tau tangles; first hippocampal, then cortical neurodegeneration. Lecanemab (2023) is the first disease-modifying therapy — modest but real.[2]
Parkinson’s disease
Loss of dopamine neurons in the substantia nigra. L-DOPA (1968) was a miracle drug; deep-brain stimulation now helps refractory patients.
5-HT
Depression
SSRIs treat symptoms imperfectly. Ketamine and psilocybin show rapid antidepressant effects via NMDA / 5-HT2A receptors — reshaping the field.[3]
~1%
Schizophrenia
Lifetime prevalence around 1% globally. Heritable, dopaminergic and glutamatergic dysregulation, but cause and definitive biomarker still elusive.
[1] WHO, Global Burden of Disease.
[2] van Dyck et al., NEJM (2023) — CLARITY-AD trial.
[3] Krystal et al., Cell (2019); Carhart-Harris et al., NEJM (2021).

Slide 13

Where to go next.

13 · Further reading
Books
Principles of Neural Science — Kandel, Schwartz et al. The standard reference.
The Idea of the Brain — Matthew Cobb. History of how we got here.
Behave — Robert Sapolsky. Neuroscience meets behavior, written for humans.
The Man Who Mistook His Wife for a Hat — Oliver Sacks. The case-study tradition.
Consciousness and the Brain — Stanislas Dehaene. The science of awareness.
Video
Neuron & action potential — YouTube search →
Consciousness & neuroscience — YouTube search →
Online
NIH BRAIN Initiative — current US funding map and data releases.
Allen Brain Atlas — high-resolution gene expression and connectivity data.
FlyWire.ai — the connectome of the fruit fly, free to explore.

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