Neuron Communication and Plasticity
Chapter 3 Part II: Neuron Communication and Plasticity
How Do Neurons Communicate and Adapt?
Neurons (nerve cells) talk to each other and change over time. This section covers:
How they send chemical messages.
The different kinds of neurotransmitters (chemical messengers) and the receptors (receiving stations) they use.
How these neurotransmitter systems affect our behavior.
How synapses (connection points) adapt, which is crucial for learning and memory.
A Chemical Message
Otto Loewi (1921): He was the first to show that neurons communicate using chemicals. He did an experiment with frog hearts.
Vagus nerve and acetylcholine (ACh): Loewi found that stimulating the vagus nerve released a chemical, later identified as ACh, that slowed the frog's heart rate.
Acetylcholine (ACh): This was the first chemical messenger found in both the brain (CNS) and the rest of the body (PNS).
In the somatic nervous system (SNS), which controls voluntary movements, ACh makes skeletal muscles contract.
In the autonomic nervous system (ANS), which controls involuntary body functions, ACh can either speed up or slow down internal organs.
The Basis of Neural Communication in a Heartbeat
Our heart rate changes to match our body's needs for energy, food, and oxygen.
Loewi's experiment showed that a chemical from the vagus nerve told the heart to slow down.
He later found two types of chemical messages involved in heart rate:
Excitatory message: Makes the heart beat faster.
Inhibitory message: Makes the heart beat slower.
How Does a Neuron Pass on a Message?
Procedure
Stimulating device: The vagus nerve of a frog's heart (heart 1) is given an electrical signal.
Fluid transfer: The fluid around heart 1 (which now contains the chemical messenger) is moved to a second container with another frog heart (heart 2).
Recording device: Heart 1's beating slows down after the nerve stimulation. Interestingly, heart 2 also slows down after receiving the fluid from heart 1, proving a chemical message was transferred.
Loewi’s Complementary Experiments
Otto Loewi also studied other important chemical messengers:
Epinephrine (EP) (also known as adrenaline): This works as a hormone (a chemical messenger in the bloodstream) to prepare the body for "fight or flight" during stress. It also acts as a neurotransmitter in the brain.
Norepinephrine (NE) (also known as noradrenaline): This acts as a neurotransmitter in the brain and in the part of the nervous system that calms the body (parasympathetic ANS). It speeds up heart rate in mammals.
Neurotransmitters
Neurotransmitter: A specific chemical released by one neuron (the sender) that travels to another target cell (the receiver), causing either an excitatory (activating) or inhibitory (slowing down) effect.
Many neurotransmitters found in the brain also act as hormones when they are in the bloodstream outside the brain. Hormones usually have slower and longer-lasting effects than neurotransmitters.
Loewi's work opened the door for scientists to find more neurotransmitters.
We don't know the exact number, but there are about 60 confirmed neurotransmitters and around 200 possible ones.
Structure of Synapses
With the invention of the electron microscope in the 1950s, scientists could see the tiny structures where neurons communicate.
They found that neurotransmitters are stored in small sacs called vesicles at the end of the axon (the sending part of the neuron).
Chemical synapse: This is the tiny gap or junction where chemical messengers (neurotransmitters) are sent from one neuron to either excite or inhibit the next neuron.
Most communication points in the mammalian brain are chemical synapses.
Chemical Synapse Depicted
Imagine two neurons talking, with a small gap between them.
Presynaptic terminal: This is the end of the sending neuron's axon. It contains the chemicals (neurotransmitters) ready to be released. "Pre" means before the synapse.
Synaptic cleft: This is the very small space between the sending (presynaptic) neuron and the receiving (postsynaptic) neuron.
Postsynaptic membrane: This is the surface of the receiving neuron (often on a dendrite or cell body). It has special receptor molecules that catch the chemical messages. "Post" means after the synapse.
Synaptic vesicle: These are small, round sacs inside the presynaptic terminal that hold the neurotransmitters.
Storage granule: These are larger compartments that hold many synaptic vesicles.
Dendritic spine: These are small bumps on the dendrites of the receiving neuron where most neurotransmitter signals are received.
Parkinson Disease
More than 50 years after James Parkinson first described the symptoms, French neurologist Jean-Martin Charcot named it Parkinson's disease.
What causes it in the brain:
There is a loss of brain cells in a specific area called the substantia nigra.
Symptoms appear when the levels of dopamine (DA), a key neurotransmitter, drop below 10% of normal in a brain region called the basal ganglia.
Studies in rats showed that destroying dopamine-producing neurons caused symptoms similar to Parkinson's disease, confirming that dopamine's pathway from the substantia nigra to the basal ganglia is crucial for movement control.
Terms to Learn: Structure of Chemical Synapses
Presynaptic membrane (the outer skin of the axon terminal, where chemicals are released)
Postsynaptic membrane (the outer skin of the dendritic spine, where chemicals are received)
Synaptic cleft (the tiny gap in between)
Tripartite synapse (a concept that includes the presynaptic neuron, postsynaptic neuron, and nearby glial cells, all working together at the synapse)
Synaptic vesicle (sacs holding neurotransmitters in the presynaptic terminal)
Storage granule (larger containers for vesicles)
Postsynaptic receptor (special proteins on the postsynaptic membrane that neurotransmitters bind to)
Anterograde synaptic transmission (the usual direction of message flow: from presynaptic to postsynaptic neuron)
Transporter (proteins that move molecules, like neurotransmitter precursors into the neuron or neurotransmitters back into the neuron)
Neurotransmission in Five Steps
This is how neurons send chemical messages:
Synthesis: Neurotransmitters are made from simpler building blocks (precursor molecules).
Packaging and storage: The newly made neurotransmitters are put into vesicles and stored, waiting for an electrical signal (action potential) to arrive.
Release: When an action potential (the electrical signal) reaches the axon terminal, it opens special calcium () channels. Calcium ions rush in, causing the vesicles to merge with the cell membrane and release their neurotransmitters into the synaptic cleft. This process is called exocytosis.
Receptor action: The released neurotransmitter floats across the synaptic cleft and binds to specific receptors on the postsynaptic neuron's membrane. This binding changes the postsynaptic neuron.
Inactivation: The neurotransmitter's job is done, so it's removed from the synaptic cleft in one of several ways.
Step 1 and 2: Neurotransmitter Synthesis, Packaging, and Storage
Where neurotransmitters come from:
Many are made right in the axon terminal from ingredients we get from our diet. Special proteins called transporters help bring these building blocks into the cell.
Some, especially larger protein-based ones called peptide transmitters, are made in the neuron's main cell body (following DNA instructions) and then moved down the axon to the terminal using microtubules (tiny cellular roads).
Types of neurotransmitter basic structures:
Peptide (protein-like)
Lipid (fat-like)
Gaseous (like nitric oxide)
Ion (like zinc ions)
Step 3: Neurotransmitter Release
When the electrical signal (action potential) arrives at the axon terminal, it causes special gates called voltage-sensitive channels to open.
Calcium () ions then rush into the cell. These calcium ions bind to a protein called calmodulin, creating a complex that signals the synaptic vesicles to fuse with the presynaptic membrane and release their neurotransmitters into the synapse via exocytosis.
Step 4: Receptor-Site Activation
Once released, the neurotransmitter crosses the synaptic cleft and attaches to specific proteins called receptors on the postsynaptic membrane:
Transmitter-activated receptors come in a few forms:
Ionotropic receptor: These are like fast-acting gates. When a neurotransmitter binds, an ion channel immediately opens, allowing ions (charged particles) to flow into or out of the cell, changing its electrical state quickly.
Metabotropic receptor: These are slower. When a neurotransmitter binds, it starts a chain reaction inside the cell, which can lead to various internal cellular changes, including eventually opening ion channels, but it takes more steps and is therefore slower.
Autoreceptor: These are special receptors located on the presynaptic neuron itself. They monitor how much neurotransmitter is being released and can regulate (either increase or decrease) further release.
Quantum (plural: quanta): Neurotransmitters are released in discrete, small packets, not continuously. Each packet is called a quantum.
Step 5: Neurotransmitter Inactivation
After stimulating the receptor, the neurotransmitter must be removed from the synaptic cleft to stop its effect and prepare the synapse for new messages. This can happen by:
Diffusion: The neurotransmitter simply floats away from the synaptic region.
Degradation: Enzymes (biological catalysts) break down the neurotransmitter into inactive parts.
Reuptake: The presynaptic neuron reabsorbs the neurotransmitter back into its terminal, often to be reused. Special transporter proteins on the presynaptic membrane perform this task.
Astrocyte uptake: Glial cells called astrocytes, which are support cells in the brain, can also absorb neurotransmitters from the synapse.
The Versatile Synapse
Synapses are incredibly diverse throughout the nervous system. They differ in their location, structure, how they work, and what cells they connect to.
This variety allows the synapse to act as a highly flexible chemical delivery system, fine-tuning how neurons communicate by connecting to different parts of the receiving neuron (dendrites, cell body, or axon).
Electrical Synapses
While most synapses are chemical, some are electrical synapses.
Gap junctions: These are direct connections between neurons, formed by channels made of proteins called connexins. Ions can flow straight from one neuron to the next through these junctions.
They act like regulated gates, opening or closing, and allow for very fast communication because there's no delay from chemical diffusion.
Electrical synapses also help glial cells and neurons communicate and allow for "mixed synapses" where both chemical and electrical signals are used.
Excitatory and Inhibitory Messages
Synapses can be specialized to either excite or inhibit the receiving neuron:
Excitatory synapse: These usually make the receiving neuron more likely to fire an electrical signal.
They are typically found on dendrites.
They have round vesicles, dense material on their membranes, a wider synaptic cleft, and a larger active zone (where neurotransmitters are released).
Inhibitory synapse: These usually make the receiving neuron less likely to fire an electrical signal.
They are generally found on the cell body.
They have flat vesicles, less dense material on their membranes, a narrower synaptic cleft, and a smaller active zone.
Dendritic Spines: Small but Mighty
Dendritic spines: These tiny bumps on dendrites are extremely important for learning and memory.
Each spine acts almost independently and can change its shape and size, making it a key part of how the brain learns and stores information.
They form the physical basis for behaviors, skills, and memories.
Problems with spine formation are linked to certain mental disabilities, and the loss of spines is seen in diseases like Alzheimer's.
Evolution of Complex Neurotransmission Systems
The idea of chemical communication might have evolved from very basic processes, like how single-celled organisms feed.
For example, secreting digestive juices (exocytosis) is similar to how neurotransmitters are released.
Capturing food (endocytosis) is similar to how neurons receive signals. This suggests a deep evolutionary root for current neurotransmission.
Classes of Neurotransmitters
Neurotransmitters are grouped based on their chemical makeup:
Small-molecule transmitters
Peptide transmitters (chains of amino acids)
Lipid transmitters (fat-based)
Gaseous transmitters (gas molecules)
Ion transmitters (ions)
Small-Molecule Transmitters
These are fast-acting neurotransmitters made in the axon terminal from nutrients in our diet. They are quickly packaged and ready for use.
Acetylcholine (ACh): Involved in muscle contraction and memory.
Amines:
Dopamine (DA): Important for reward, motivation, and motor control (lack of DA causes Parkinson's).
Norepinephrine (NE) (noradrenaline): Involved in alertness, arousal, and mood.
Epinephrine (EP) (adrenaline): Works as both a hormone (stress response) and a neurotransmitter.
Serotonin (5-HT): Affects mood, sleep, appetite, and learning.
Amino acids: These are the building blocks of proteins and also act as neurotransmitters.
Glutamate (Glu): The main excitatory neurotransmitter in the brain, crucial for learning and memory.
Gamma-aminobutyric acid (GABA): The main inhibitory neurotransmitter in the brain, helps calm brain activity.
Glycine (Gly): Another inhibitory neurotransmitter, mainly in the spinal cord.
Histamine (H): Involved in wakefulness and immune responses.
Purines:
Adenosine: Can act as an inhibitory neurotransmitter, affecting sleep and reducing