Chapter 2: Synapses & Neurotransmitters

Discover how neurons communicate through chemical signals

How do neurons talk to each other?

Neurons communicate through specialized junctions called synapses, using chemical messengers called neurotransmitters. This process is fundamental to everything your brain does - from simple reflexes to complex thoughts and emotions.

In this exploration, you'll discover:

Start by selecting a tab below to begin your exploration!

Synaptic Structure: The Communication Junction

Presynaptic Terminal P/Q N Ca²⁺ Synaptic Cleft 20-40 nanometers Postsynaptic Membrane PSD AMPA AMPA NMDA Na⁺ K⁺ ATP ATP Action Potential Signal Direction

💡 Interactive: Click on any part of the synapse to learn more about its function

Key Synaptic Components

Synapses are highly specialized structures that enable precise chemical communication between neurons:

Presynaptic Terminal

Contains synaptic vesicles, Ca²⁺ channels, and release machinery. Action potentials trigger neurotransmitter release here.

Synaptic Vesicles

Membrane-bound organelles storing ~5,000-10,000 neurotransmitter molecules each. Ready-releasable pool contains ~10-20 vesicles.

Synaptic Cleft

20-50 nanometer gap where neurotransmitters diffuse. Contains enzymes (AChE) and transporters for signal termination.

Postsynaptic Membrane

Contains neurotransmitter receptors and ion channels. Generates EPSPs or IPSPs based on receptor type.

Receptors & Channels

Ionotropic receptors (fast, ~1ms) directly gate ion channels. Metabotropic receptors (slow, ~100ms) use second messengers.

📡 Watch: The simulation shows medically accurate timing and molecular interactions during synaptic transmission. Each step is based on real neuroscience research!

Synaptic Transmission: Step-by-Step Process

Interactive Transmission Timeline

Follow the precise sequence of events during synaptic transmission. Each step occurs within milliseconds:

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Transmission Steps

1. Action Potential Arrival (t=0ms)

Action potential depolarizes presynaptic terminal to +30mV, opening voltage-gated Ca²⁺ channels.

  • Membrane depolarization activates Ca²⁺ channels
  • Ca²⁺ influx increases from 0.1μM to 10-100μM

2. Calcium Influx (t=0.1-0.3ms)

Ca²⁺ enters through N-type and P/Q-type channels, binding to synaptotagmin sensors.

  • Synaptotagmin acts as Ca²⁺ sensor
  • SNARE proteins prepare for vesicle fusion

3. Vesicle Fusion (t=0.2-0.5ms)

Ca²⁺-triggered exocytosis: vesicles fuse with presynaptic membrane via SNARE complex.

  • Fusion pore opens (~1-2nm diameter)
  • ~5,000-10,000 neurotransmitter molecules released

4. Neurotransmitter Diffusion (t=0.1-1ms)

Neurotransmitters diffuse across 20-50nm synaptic cleft, reaching peak concentration in ~100μs.

  • Diffusion time depends on cleft width
  • Concentration peaks at ~1mM in cleft

5. Receptor Binding (t=0.1-2ms)

Neurotransmitters bind to postsynaptic receptors, causing conformational changes.

  • Ionotropic: Direct channel opening
  • Metabotropic: G-protein activation

6. Postsynaptic Response (t=1-10ms)

Ion channels open, generating EPSP or IPSP. Signal integration determines if action potential fires.

  • EPSP: Na⁺/Ca²⁺ influx, depolarization
  • IPSP: K⁺ efflux or Cl⁻ influx, hyperpolarization

7. Signal Termination (t=1-100ms)

Neurotransmitter removal by reuptake, enzymatic degradation, or diffusion.

  • Reuptake transporters (DAT, SERT, NET)
  • Enzymes (AChE, MAO, COMT)

Neurotransmitters: The Brain's Chemical Messengers

Over 100 different neurotransmitters have been identified, each with specific functions and effects. They can be classified by chemical structure and function:

Amino Acids

Glutamate

Primary excitatory neurotransmitter (~80% of synapses)

Function: Learning, memory, synaptic plasticity

Receptors: AMPA, NMDA, kainate, mGluR

GABA

Primary inhibitory neurotransmitter (~20% of synapses)

Function: Anxiety control, sleep, seizure prevention

Receptors: GABA-A (ionotropic), GABA-B (metabotropic)

Glycine

Inhibitory in spinal cord and brainstem

Function: Motor control, reflexes

Monoamines

Dopamine

Reward, motivation, motor control

Pathways: Nigrostriatal, mesolimbic, mesocortical

Disorders: Parkinson's, schizophrenia, addiction

Serotonin (5-HT)

Mood, sleep, appetite, pain

Receptors: 14 subtypes (5-HT1-7)

Disorders: Depression, anxiety, migraine

Norepinephrine

Attention, arousal, stress response

Source: Locus coeruleus

Cholinergic

Acetylcholine (ACh)

First discovered neurotransmitter (1921)

CNS: Attention, learning, memory

PNS: Neuromuscular junction, autonomic

Receptors: Nicotinic (ionotropic), muscarinic (metabotropic)

Degradation: Acetylcholinesterase (AChE)

Neuropeptides

Endorphins

Natural opioids, pain relief, euphoria

Function: Stress response, reward

Substance P

Pain transmission, inflammation

Function: Nociception, mood

Purines

ATP

Co-transmitter, fast synaptic transmission

Function: Pain, autonomic control

Adenosine

Sleep regulation, neuroprotection

Function: Caffeine antagonist

Gaseous

Nitric Oxide (NO)

Retrograde messenger, vasodilation

Function: LTP, blood flow

Neurotransmitter Receptors: Signal Detection

Neurotransmitter receptors are specialized proteins that detect and respond to chemical signals. They fall into two main categories:

Ionotropic Receptors

Ligand-gated ion channels that directly open when neurotransmitter binds

AMPA Receptors

Glutamate receptors, fast excitatory transmission

Ions: Na⁺, K⁺ | Speed: ~1ms

NMDA Receptors

Glutamate + glycine, voltage-dependent

Ions: Na⁺, K⁺, Ca²⁺ | Function: LTP

GABA-A Receptors

Primary inhibitory receptors

Ions: Cl⁻ | Drugs: Benzodiazepines

Nicotinic Receptors

Acetylcholine, neuromuscular junction

Ions: Na⁺, K⁺ | Location: NMJ, ganglia

Metabotropic Receptors

G-protein coupled receptors that use second messenger systems

Muscarinic Receptors

Acetylcholine, autonomic nervous system

Types: M1-M5 | Speed: ~100ms

Dopamine Receptors

D1-like (D1, D5) and D2-like (D2, D3, D4)

Function: Motor control, reward

Serotonin Receptors

14 subtypes (5-HT1-7), diverse functions

Function: Mood, sleep, appetite

mGluR

Metabotropic glutamate receptors

Types: Group I, II, III | Function: Modulation

Synaptic Integration: Computing with Neurons

Spatial and Temporal Summation

Neurons integrate multiple synaptic inputs to determine whether to fire an action potential:

Spatial Summation

Multiple synapses active simultaneously

  • Different locations on dendrites
  • EPSPs and IPSPs add algebraically
  • Depends on input resistance

Temporal Summation

Same synapse active repeatedly

  • Rapid succession of inputs
  • Depends on membrane time constant
  • Facilitation vs. depression

Synaptic Plasticity

Activity-dependent changes in synaptic strength

  • LTP: Long-term potentiation
  • LTD: Long-term depression
  • Hebbian rule: "Cells that fire together, wire together"

Clinical Significance

Synaptic Disorders

  • Myasthenia Gravis: Autoimmune attack on ACh receptors
  • Lambert-Eaton: Reduced Ca²⁺ channel function
  • Botulism: Blocks ACh release

Drug Targets

  • SSRIs: Block serotonin reuptake
  • Benzodiazepines: Enhance GABA-A function
  • Antipsychotics: Block dopamine receptors
  • Cholinesterase inhibitors: Alzheimer's treatment

Research Applications

  • Optogenetics: Light-controlled neurotransmitter release
  • Patch-clamp: Single channel recordings
  • Two-photon microscopy: Live synaptic imaging