Synapses and Synaptic Transmission

What is a snyapse

Specialized point of contact between a neuron and another neuron, muscle cell, or gland
Information is transmitted from one neuron (presynaptic) to another cell (postcynaptic)

What are the types of synapses

Electrical
Chemical

Synapses: electrical

Gap junction
Pres and Postsynaptic membranes (3nm apart)
Connexins
Pores big and fast
Cardiac, smooth muscle, glands, glia cells

Connexins

Channel proteins that allow direct communication

Synapses: chemical

Most synaptic transmission in the human nervous system
Presynaptic terminal
Synaptic cleft
Postsynaptic terminal
Neurotransmitter
Axo-somatic, Axo-dendritic, Axo-axonic connections

What makes up the presynaptic terminal

Axon terminal
Terminal bouton

What makes up the postsynaptic terminal

Membrane of target neuron

What are neurotransmitters

Chemicals contained in small vesicles for communication

Events at a chemical synapse

Action potential reaches presynaptic terminal
Ca++ enters presynaptic terminal
Vesicles move toward release sites
Presynaptic terminal releases neurotransmitters (exocytosis)
Neurotransmitters bind with postsynaptic membrane receptor
Postsynaptic membrane channels change shape allowing ion to enter postsynaptic cell or activates intracellular messengers
Neurotransmitter is broken down, diffused or re-uptake (endocytosis) to end transmission

Electrical (local) potentials at synapes

Excitatory postsynaptic potential (EPSP)
Inhibitory postsynaptic potential (IPSP)

Excitatory Postsynaptic Potential

Causes depolarization
Summation = action potential

Inhibitory Postsynaptic Potential

Causes hyperpolarization
Involves influx of Cl- or efflux or K+

What does EPSP and IPSP help regulate

Excitability of nervous system

Presynaptic facilitation and inhibition

When the amount of neurotransmitter that is released (increased or decreased) is influenced by previous activity of an axo-axonic synapse

Presynaptic facilitation

Presynaptic axon releases neurotransmitter that causes slight depolarization and influx of Ca++ prolonging/enhancing the effect action potential when it arrives at the axon terminal

Presynaptic inhibition

Presynaptic axon releases neurotransmitter that causes slight hyperpolarization reducing influx of Ca++ reducing the effects of action potential when it arrives at the axon terminal

Types of synaptic receptors

Ligand-Gated Ion Channels
G-Protein Mediated Receptors (modulators)

Ligand-Gated Ion Channels

Proteins that function like a gate
Gate open upon binding of neurotransmitter
Fast acting
Inactivated when neurotransmitter releases
Majority of synaptic activity is mediated by ligand-gated channels

G-Protein Mediated Receptors

More complex
Slower acting
Generally longer acting modulators of neural activity
Involved in second-messenger system

Second Messenger System

G-protein activates intracellular
The target protein then produces a second messenger

What can second messenger initiate

Opening of membrane ion channels
Activation of genes that cause increase synthesis of cellular products
modulation of Ca++ concentration in cell

Cyclic adenosine monophosphate (cAMP)

Activation of adenyl cyclase converts ATP to cAMP
cAMP then modulates membrane receptors and gene expression

Arachidonic Acid

G-protein activation of enzyme phospholipase A2
Phospholipase A2 results in production of arachidonic acid
Arachidonic acid leads to production of prostaglandins which regulate vasodilation and inflammation
Aspirin and other NSAIDs inhibit enzyme in G-protein mediated cascade

Neurotransmitters and Neuro Modulators

Most neurotransmitters are classified as amino acids or the derivatives, amines, and peptides. One exception is the cholinergic transmitter acetylcholine
Neuro-modulators while technically a neurotransmitter tend to be longer acting and/or cause changes in larger networks of neurons and utilize G-protein mediated pathways

Are neurotransmitters fast or slow acting most of the time

Fast acting

Are neuro-modulators fast or slow acting most of the time

Slow acting

Common neurotransmitters

Acetylcholine (PNS)
GABA
Glycine
Glutamate

Common neuro-modulators

Dopamine
Serotonin
Norepinephrine
Substance P
Endorphins
Acetylcholine (CNS)

Acetylcholine

Major role in transmitting information in the PNS and at neuromuscular junctions
Acts as neuromodulator in CNS

GABA

Major inhibitory neurotransmitter in CNS
Amino Acid
GABAa and GABAb receptors

GABAa receptor

Cl- channels open causing hyperpolarization
Benodiazepines (valium) and Barbituates

GABAb receptors

Linked to ion channels via second messengers
Baclofen increases GABA release from presynaptic terminals in spinal cord

Glycine

Inhibits postsynaptic membranes primarily in brain stem and spinal cord
Amino acid

Glutamate

Major excitatory neurotransmitter of CNS
Amino Acid
Activates NMDA (N-methyl-D-aspartate) receptor
NMDA receptor implicated in neuroplasticity and long term potentiation
Can cause excitoxicity and death of neurons with overexcitation

Dopamine

Has effects on motor activity, motivation and cognition, pleasure and reward systems
Monoamine
Major source of dopamine is substantia nigra and ventral tegmental area (VTA)
Loss of dopamine primary cause of Parkinson’s

Serotonin

Adjusts the general arousal level and suppresses sensory information
Monoamine

Norepinepherine

Vital role in active surveillance of surroundings by increasing attention to sensory information
Essential in producing the “flight or fight” reaction to stress
Monamine

Where is the highest levels of norephinepherine

Associated with vigilance

Where is the lowest levels of norepinepherine

Occur during sleep

Substance P

Within the spinal cord
Acts as a neurotransmitter in the nocioceptive pathway
At other sites, substance P acts as a neuromodulator, producing long-duration excitation of postsynaptic membranes
Peptide

Where are endorphins found

In areas with opiate receptors including the substania gelatinosa, hypothalamus, periventricular gray, and periaqueductal gray

What is the primary action of endorphins

Inhibition of slow nocioceptive information

Endorphins are

Peptides

Clinical considerations: neurotransmitter agonist and antagonists

Most drugs effecting the nervous system either mimic (agonist) or block (antagonist) the effects of neurotransmitters

Examples of neurotransmitter agonist and antagonists

Botulinum toxin A
Baclofen
Propranolol
Sinemet
SSRI’s
MAOI’s

Botulinum toxin A

Block release of ACh

Baclofen

Agonist for GABAb receptors

Propranolol

Blocks (antagonist) Beta1 receptors for norepinephrine

Sinemet

L-dopa converts to dopamine in CNS

SSRI’s

Prolong the lift of serotonin in the synaptic cleft

MAOI’s

Prevent break down of the serotonin, dopamine, and norepinephrine

Diseases involving synaptic transmission and neurotransmitters: Parkinson’s

Dopamine

Diseases involving synaptic transmission and neurotransmitters: Lambert-Eaton Syndrome

Small cell carcinoma of lung
Anti-bodies to Ca++ channels

Diseases involving synaptic transmission and neurotransmitters: Myasthenia Gravis

Antibodies to nicotinic ACh receptors of muscle cells

Diseases involving synaptic transmission and neurotransmitters: Depression

Abnormalities in levels of serotonin, dopamine, and norepinephrine