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Synaptic Transmission
Focuses on how a presynaptic neuron conveys information to a postsynaptic neuron, typically via neurotransmission.
Overview of neurotransmitters.
Neurotransmitters
Examples of neurotransmitters and their functions:
Serotonin: Targeted by SSRIs.
Dopamine: Associated with pleasure.
Acetylcholine: Excites muscles.
Adrenaline/Noradrenaline: Involved in energy and excitement; noradrenaline more prevalent in the brain.
Neurotransmitters can excite or inhibit postsynaptic neurons or affect muscles/glands (e.g., adrenaline or acetylcholine).
Electrical Synapses (Gap Junctions)
Not as prevalent as chemical synapses but still important.
Gap junctions: Channels between cell membranes of adjacent cells allowing direct current to pass.
Allow direct currents to pass between cells.
Found in neurons and other cell types (e.g., astrocytes).
Waves of calcium pass through cells coupled by gap junctions in astrocytes (slower than neurotransmission).
Consist of channel proteins that bring cell membranes very close together.
Ions (cations, sodium, potassium, calcium) can pass through; larger proteins and possibly second messengers cannot due to narrow channels.
Chemical Synapses
Presynaptic neuron releases neurotransmitter that acts on the postsynaptic cell or effector organ.
Vast majority of synapses.
Action potentials depolarize the presynaptic membrane.
Voltage-gated calcium channels open, leading to calcium influx.
Calcium triggers synaptic vesicles to fuse with the membrane (exocytosis) and release neurotransmitters (e.g., glutamate, noradrenaline, acetylcholine, dopamine).
Released neurotransmitters bind to receptors on the postsynaptic membrane.
Two primary receptor types:
Ligand-gated ion channels: Neurotransmitter binding opens the channel (e.g., glutamate receptors, acetylcholine receptors on muscle).
Channel opening (e.g., sodium channels) leads to depolarization.
Neurotransmitter is removed from the synaptic cleft via reuptake into the presynaptic neuron for recycling.
Direct Neurotransmission
The neurotransmitter receptor is a ligand gated channel, meaning the ligand, the neurotransmitter, when it binds, can open the channel.
Vesicle Fusion and Neurotransmitter Release
Electron micrographs show vesicle fusion with the plasma membrane and release of contents (exocytosis).
Neurotransmission Process
Depolarization arrives, calcium channels open, calcium enters, neurotransmitter is released, binds to postsynaptic receptors, and ion channels open.
Postsynaptic Potentials (PSP)
EPSP (Excitatory Postsynaptic Potential)
Small depolarization caused by opening neurotransmitter-gated ion channels.
One EPSP is insufficient to trigger an action potential.
Excitatory postsynaptic current (EPSC) is measurable during channel opening.
IPSP (Inhibitory Postsynaptic Potential)
Caused by inhibitory neurotransmitters (GABA, glycine) opening chloride channels.
Chloride influx leads to hyperpolarization, reducing cell excitability.
Inhibitory postsynaptic current (iPSC) is measurable during channel opening.
Can also result from opening more potassium channels.
Summation
Multiple PSPs are needed to reach the threshold for voltage-gated sodium channels and trigger an action potential.
Temporal Summation
Several EPSPs from one synapse add up over time to reach the threshold.
Spatial Summation
EPSPs from multiple synapses add up to reach the threshold.
Integration of Signals
Inputs from excitatory and inhibitory neurons can cancel each other out, blocking excitation.
Comparison of Postsynaptic Potentials and Action Potentials
Feature
Postsynaptic Potential (PSP)
Action Potential (AP)
Type
Excitatory or Inhibitory
Depolarization
Magnitude
Graded
All-or-nothing
Location
Cell body/dendrites
Axon hillock
Summation
Yes
No
Ion Channels
Ligand gated
Voltage gated
Ion Distribution
Extracellular:
High concentrations of sodium (Na+) and chloride (Cl−).
Intracellular:
High concentration of potassium (K+).
Voltage-Gated Sodium Channels
Upon opening, sodium rushes into the cell due to its high extracellular concentration and concentration gradient.
Types of Synaptic Transmission
Direct Synaptic Transmission
Neurotransmitter opens an ion channel within the neurotransmitter receptor.
Receptor is a ligand-gated ion channel.
Quick process.
Examples: glutamate receptors, acetylcholine receptors in muscle.
Indirect Synaptic Transmission
Involves a second messenger.
Neurotransmitter receptor activates a G protein, which then affects a signal transduction pathway.
Slower process.
Membrane Protein Receptors
Ion channel-linked receptors and G protein-coupled receptors are key in neurotransmission.
Not all membrane proteins are involved in neurotransmission (e.g., insulin receptors).
Direct Synaptic Transmission Mechanism
Ligand gated ion channels, also called ion channel linked receptor, are cation channels permeable to sodium, potassium, and sometimes calcium.
Examples: acetylcholine acting on nicotinic receptors in skeletal muscle, glutamate acting on glutamate receptors in the brain.
Neurotransmitter binding opens the channel.
Monosodium Glutamate (MSG)
In some individuals, MSG can pass the blood-brain barrier, leading to over-excitation and headaches.
Postsynaptic Potential
Neurotransmitter opening an ion channel leads to a graded postsynaptic potential (EPSP or IPSP), depending on the ion channel type.
** Channels passing sodium or calcium result in depolarization.
** Chloride channels cause hyperpolarization.
Inhibitory Neurotransmitters
GABA and glycine open chloride channels.
Glycine
Predominantly in the spinal cord, important for inhibition.
Blocking glycine receptors (e.g., with strychnine) leads to excessive excitation and spasticity.
Glutamate
More abundant in the brain than glucose.
Can be converted into GABA(gamma aminobutyric acid), an inhibitory neurotransmitter.
GABA increases activity when drinking alcohol, and sleeping pills and anti-seizure pills strengthen the effect of GABA on the inhibitory neurotransmitter receptors.
GABA opens chloride channels in the brain.
Indirect Synaptic Transmission
Neurotransmitter binds to a receptor, activating a signal transduction pathway involving a second messenger.
Can lead to EPSPs, IPSPs, muscle contraction, or relaxation.
G Protein-Coupled Receptors
Glutamate receptors coupled to G proteins.
G proteins are heterotrimeric proteins that bind GTP when activated.
Effector can be an ion channel (calcium or potassium channel).
Example: acetylcholine acting on muscarinic receptors to slow down the heart by opening potassium channels.
G proteins can couple to secondary messenger systems like cAMP or inositol triphosphate, increasing intracellular calcium.
Second Messengers
cAMP: plays a role in the heart and smooth muscles.
Intracellular calcium: important for muscles and exocytosis
Neurotransmitter Classification
Acetylcholine
Acts on skeletal muscle (direct opening of cation channels via nicotinic acetylcholine receptors).
Acts on smooth muscles and the heart through muscarinic receptors (indirect).
Not an amino acid; made from choline.
Amine Transmitters (Derived from Amino Acids)
Noradrenaline and Dopamine
Derived from tyrosine.
Dopamine is a precursor to noradrenaline.
Noradrenaline: Important for staying awake and motivated.
Dopamine: Increased by drugs blocking reuptake; important for movement (deficient in Parkinson's disease) and pleasure.
Serotonin
Derived from tryptophan; also called 5-hydroxytryptamine (5-HT).
Mostly acts on receptors with indirect transmission, except for the 5-HT3 receptor (ion channel).
Involved in digestion, vomiting, sleep, eating, sex drive; affected by SSRIs.
Neurotransmitter Removal
Diffusion out of the synaptic cleft.
Enzymatic breakdown (e.g., acetylcholine esterase breaking down acetylcholine).
Acetylcholine esterase inhibitors (nerve gases, insecticides) increase acetylcholine levels, leading to muscle cramps and paralysis.
Drugs can also be used to get the GI tract into motion and for glaucoma.
Recycling/uptake back into the presynaptic cleft (e.g., via norepinephrine transporter or serotonin transporter).
Glial cells or astrocytes take up amino acid neurotransmitters like glutamate.
SSRIs block serotonin reuptake; some also block noradrenaline uptake.
Acetylcholine Release Mechanism
Involves opening of voltage gated calcium channels to trigger intracellular calcium levels, going up and that triggers release.
Study Recommendations
Ask yourself questions about neurotransmitters.
What is the main function, which ones elicit EPSPs, which ones do IPSPs.
Consider which neurotransmitters play a role in the brain versus the periphery.