How the Brain Works: Neurons, Synapses & Behavior

Neuroscience as the study of the black box

While evolution, genetics, and ethology explain behavior from different angles, neuroscience focuses on what happens inside the brain milliseconds before an action occurs—the cellular and molecular mechanisms that drive behavior.

Course framework: multiple scientific approaches to behavior

The course uses the metaphor of 'why the chicken crossed the road' to show how different disciplines approach the same question: evolution asks how it evolved over millions of years; genetics asks which genes control it; ethology observes it in nature; neuroscience asks what's happening in the brain.

Five scientific approaches to understanding behavior

Central vs. peripheral nervous system

The nervous system divides into the central nervous system (brain and spinal cord) and the peripheral nervous system (motor and sensory nerves outside the spinal cord, including automatic functions like heartbeat and digestion).

Brainstem and cerebellum: relay and motor learning

The brainstem relays information between brain and spinal cord. The cerebellum, highly wrinkled and densely packed with cells, controls motor movement and learns from mistakes—when you learn to play piano or shoot a basketball, the cerebellum corrects errors over repeated trials.

Four lobes of the cortex and their functions

The cortex is divided into four lobes: frontal (plans actions, controls movement), parietal (processes touch sensation), temporal (processes hearing, supports memory), and occipital (processes vision). Each lobe is further specialized by body part or sensory modality.

Functional specialization of cortical lobes

Motor cortex organization mirrors the body

The motor cortex is organized somatotopically: different regions control different body parts (foot, leg, trunk, arms, face), arranged in the same spatial order as the body. Cortical area size reflects the precision needed—fingertips have larger cortical representation than the back.

Limbic system: emotion, learning, and memory

The limbic system sits beneath the cortex and above the brainstem, controlling emotion, learning, and memory. Two key structures are the hippocampus (forms new memories) and amygdala (processes fear and anxiety).

Hippocampus and memory: the case of Patient HM

Patient HM had severe epilepsy and underwent surgery to remove his hippocampus on both sides. Post-surgery, his seizures stopped, but he could no longer form new memories—meeting the same nurse daily felt like meeting her for the first time. However, childhood memories remained intact, proving the hippocampus is essential for forming new memories but not storing old ones.

Patient HM: the discovery that hippocampus forms new memories

Amygdala: fear and anxiety processing

The amygdala, two almond-shaped structures in the limbic system, light up when viewing fearful or angry faces but not happy faces. It is critical for detecting fear and forming anxiety responses, as shown by brain imaging studies of people smelling fear-scent versus exercise-scent.

Hypothalamus and pituitary: hormone control and the four Fs

The hypothalamus and pituitary gland sit at the brain's base and control hormone release to the body. The hypothalamus regulates the 'four Fs': fight, flight, feeding, and reproductive behavior.

The four Fs: behaviors controlled by the hypothalamus

Santiago Ramón y Cajal and the neuron doctrine

Until the late 1800s, the brain was thought to be a continuous web of interconnected material. Ramón y Cajal used Golgi staining to visualize individual cells and drew detailed pictures proving the brain is made of discrete individual cells (neurons), not a connected mesh. This discovery earned him god-like status in neuroscience.

Glia: the 90% of brain cells doing essential work

Ninety percent of brain and spinal cord cells are glia, not neurons. Glia were named 'glue' because early scientists thought they just stuck neurons together, but they actually perform critical functions: astrocytes supply nutrients and regulate neuron firing; oligodendrocytes and Schwann cells wrap axons to speed signal transmission; microglia act as the brain's immune system.

Cell composition of the brain and spinal cord

Neuron scale: 100 billion neurons with quadrillion synapses

The human brain contains roughly 100 billion neurons, each with about 10,000 connections (synapses) to other neurons. This yields approximately one quadrillion synapses—more than 1,000 times the number of stars in the Milky Way galaxy (300 billion).

Scale of neural connectivity vs. cosmic scale

Neuron anatomy: dendrites, soma, axon hillock, axon, terminal

A neuron has dendrites (receive input from other cells), soma/cell body (contains nucleus), axon hillock (decision point for firing), axon (wire sending signal), and terminal (releases signal to next cell). Information flows from dendrites through the cell body to the axon terminal.

Information flow through a neuron

Resting potential: neurons stay quiet by pumping out positive ions

Neurons maintain a resting state by using pumps to expel positive ions (like sodium and potassium) outside the cell, leaving the inside negatively charged. This electrical imbalance keeps the neuron quiet until it receives a signal.

Depolarization: incoming signals make the neuron less negative

When a neurotransmitter from another neuron binds to a receptor on the dendrite, it opens a channel allowing positive ions to flow in. This makes the inside of the neuron less negative (depolarized). Multiple signals or frequent signals can accumulate enough positive charge to trigger firing.

All-or-nothing action potential at the axon hillock

The axon hillock acts as a threshold detector. If enough positive charge accumulates there, voltage-gated channels open, allowing a flood of positive ions to rush in. This triggers a self-reinforcing cascade (positive feedback) that propagates down the axon. If threshold is not reached, the neuron stays quiet. There is no in-between—it is all-or-nothing.

Repolarization: positive ions flow out to restore resting state

After the action potential peaks, different ion channels open to let positive ions flow out of the cell, and pumps continue expelling positive ions. This restores the negative resting potential, allowing the neuron to fire again if needed.

The synapse: where neurons communicate chemically

The synapse is the junction between a presynaptic neuron (sender) and postsynaptic neuron (receiver). Because neurons are separate cells, they cannot communicate electrically across the gap; instead, the presynaptic neuron releases neurotransmitters that bind to receptors on the postsynaptic dendrite.

Neurotransmitter release: vesicles dump their cargo

When an action potential reaches the axon terminal, it triggers an influx of calcium ions. This causes vesicles (membrane-bound sacs containing neurotransmitter molecules) to move to the cell membrane and release their contents into the synaptic cleft via exocytosis.

Immediate synaptic effects: ion channels open or close

When a neurotransmitter binds to a receptor on the postsynaptic dendrite, it can trigger two types of immediate effects: opening channels for positive ions (excitatory, promoting action potential) or opening channels for negative ions (inhibitory, suppressing action potential).

Long-term synaptic effects: strengthening synapses through gene expression

Beyond immediate ion channel opening, neurotransmitter binding can activate transcription factors that increase production of new receptors or ion channels on the postsynaptic membrane. More receptors make the synapse more responsive to the same amount of neurotransmitter, strengthening the connection.

One neurotransmitter, many functions: brain compartmentalization

Although there are only a few hundred neurotransmitters (not 100 billion), each can have diverse functions because the brain is compartmentalized—different neural networks in physically separated regions use the same neurotransmitter for different purposes. Like 26 letters creating infinite messages, a few neurotransmitters enable vast behavioral complexity.

Criteria for identifying a neurotransmitter

To prove a molecule is a neurotransmitter, scientists must demonstrate: (1) it localizes in axon terminals, (2) it is released following an action potential, and (3) it induces an influx of charge in the postsynaptic dendrite after binding to a receptor.

Three criteria for identifying a neurotransmitter

Dopamine: reward, pleasure, and motor control

Dopamine is most commonly associated with reward and pleasure but has diverse functions across different brain regions. It is involved in motivation, motor control, and other processes depending on which neural network is using it.

Epinephrine (adrenaline) and norepinephrine: fight-or-flight

Epinephrine and norepinephrine are structurally similar and functionally interchangeable. Both are released during threat or stress, triggering the fight-or-flight response—either confronting danger or fleeing from it.

Serotonin: mood, sleep, and appetite

Serotonin regulates sleep, appetite, and mood, though its functions extend beyond these. It is a key target for antidepressant medications.

Acetylcholine: neuromuscular junction and cognitive function

Acetylcholine is released at the neuromuscular junction to trigger muscle contraction, enabling all movement. It also plays roles in attention and memory in the brain.

GABA and glutamate: inhibition and excitation

GABA is the most common inhibitory neurotransmitter (suppresses action potentials), while glutamate is the most common excitatory neurotransmitter (promotes action potentials). Both have diverse functions across many brain regions.

The two most common neurotransmitters in the brain

Neuropharmacology: external manipulation of synaptic events

Neuropharmacology uses drugs or compounds to increase or decrease synaptic strength for research or therapeutic purposes. The goal is to understand neurotransmitter function or correct disease states.

Strengthening synapses: increase release, block reuptake, enhance receptors

Synaptic strength can be increased by: (1) increasing neurotransmitter synthesis or release, (2) blocking reuptake (the recycling of used neurotransmitter back into the presynaptic neuron) or degradation, or (3) enhancing receptor affinity so the postsynaptic neuron responds more strongly to the same amount of neurotransmitter.

Three ways to strengthen synaptic communication

Weakening synapses: block release, block receptors, decrease affinity

Synaptic strength can be decreased by blocking neurotransmitter release, blocking receptors, or decreasing receptor affinity, preventing the postsynaptic neuron from responding to the neurotransmitter.

Hallucinogens mimic neurotransmitters: LSD, psilocybin, mescaline

Hallucinogenic drugs like LSD, psilocybin, and mescaline structurally resemble serotonin. They bind to serotonin receptors, triggering altered perception and consciousness by hijacking the brain's serotonin signaling.

Reuptake and degradation: clearing used neurotransmitters

After a neurotransmitter has done its job, it must be removed from the synapse. This happens via reuptake (the presynaptic neuron pumps it back in for repackaging) or enzymatic degradation. Degradation products appear in cerebrospinal fluid, blood, and urine—useful markers for diagnosing neurotransmitter imbalances.

Parkinson's disease: dopamine deficit and treatment trade-offs

Parkinson's disease involves insufficient dopamine in motor control regions. Increasing dopamine globally can alleviate motor symptoms but may increase dopamine in other regions (mesolimbic pathway), causing schizophrenia-like symptoms. This illustrates the challenge of brain compartmentalization: treating one region's deficit risks side effects in others.

The challenge of treating localized neurotransmitter deficits

Nicotine and acetylcholine receptors: addiction and neuromuscular effects

Nicotine binds to nicotinic acetylcholine receptors, mimicking acetylcholine. Chronic nicotine exposure causes receptors to hide (downregulation), leading to addiction as the brain adapts. At the neuromuscular junction, excessive nicotine binding can prevent muscle contraction, causing paralysis.

Different brain regions specialize in different functions

The brain is organized hierarchically and regionally: different lobes process different sensory modalities, different subcortical structures control emotion and memory, and different neural networks use the same neurotransmitter for different purposes.

Neurons are individual cells, not a continuous web

Ramón y Cajal's discovery that the brain is made of discrete neurons (not a connected mesh) revolutionized neuroscience. Neurons are the functional units of the nervous system.

Action potentials are all-or-nothing electrical events

Neurons either fire or do not fire; there is no in-between. The axon hillock integrates incoming signals and, if threshold is reached, triggers a self-propagating action potential down the axon.

Synaptic communication is chemical, not electrical

Because neurons are separate cells, they communicate via neurotransmitters released from the presynaptic terminal and received by receptors on the postsynaptic dendrite. This chemical synapse is the basis of all neural computation.

Neurotransmitter effects depend on receptor type and brain location

The same neurotransmitter can be excitatory or inhibitory depending on the receptor it binds to. The same neurotransmitter in different brain regions produces different behavioral effects due to compartmentalization.

Pharmacological interventions have widespread side effects

Because neurotransmitters are used in multiple brain regions for different functions, drugs that increase or decrease a neurotransmitter globally will affect all those regions, potentially causing unwanted side effects in areas unrelated to the target disorder.