Synapses and Neurotransmission

The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. The neuron that sends the signal to another neuron is called the presynaptic neuron, while the neuron that receives the signal is called the postsynaptic neuron. The plasma membranes of the 2 neurons are placed very close together and are held in place by synaptic adhesion molecules that proceed from both the presynaptic and postsynaptic neurons. The space between the 2 neurons is called the synaptic cleft. The molecules that mediate the interaction are called neurotransmitters.

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Synapses

Anatomy of the synapse

In the CNS, a synapse is a structural part of a neuron that passes an electrical or chemical signal to another neuron or to a target cell.

Neuron structure:

  • Cell membrane
  • Cell body
  • Dendrites
  • Axon
  • Myelin sheath
  • Nodes of Ranvier (between myelin sheaths)
  • Synapse
Anatomy of a neuron

Anatomy of a neuron

Image: “Anatomy of the neuron” by Phil Schatz. License: CC BY 4.0

At a synapse:

  • A signal-passing neuron (the presynaptic neuron) 
  • The target neuron (the postsynaptic neuron)
  • The 2 neural membranes create a synaptic cleft that carries out the signaling process (neurotransmission)
An-overview-of-neurotransmission-at-the-synapse

An overview of neurotransmission at the synapse

Image by Lecturio.

Synapses by location

  • Axodendritic: axon to a dendrite
  • Axosomatic: axon to a soma
  • Axosecretory: axon to a blood vessel
  • Axoaxonic: axon to another axon
  • Dendrodendritic: dendrite to another dendrite
  • Axoextracellular: axon with no connection
Types of synapses

Different types of synapses by location

Image: “Synapse types” by BruceBlaus. License: CC BY 3.0

Types of synapses

Electrical synapses:

  • Gap with channel proteins connecting 2 neurons so that an electrical signal can travel over the synapse.
  • 2 neurons connected through special channels called gap junctions 
  • Unregulated
  • Allow signals to be transferred rapidly between cells
  • Found in specialized locations:
    • Heart
    • Smooth muscle
    • Pulp of the tooth
    • Retina of the eye

Chemical synapses:

  • Gap between 2 neurons where information passes chemically in the form of neurotransmitter molecules
  • Contains: 
    • Presynaptic membrane
    • Synaptic cleft
    • Postsynaptic membrane
  • Most common chemical synapse: 
    • Neuromuscular junction 
    • Formed by the contact between a motor neuron and a muscle fiber
  • Postsynaptic conductance or postsynaptic potentials (PSPs)
    • Excitatory postsynaptic potentials (EPSPs): PSPs that ↑ the likelihood of a postsynaptic action potential occurring
    • Inhibitory postsynaptic potentials (IPSPs): PSPs that ↓ the likelihood of a postsynaptic action potential occurring
    • Whether a postsynaptic response is an EPSP or an IPSP depends on:
      • The type of channel that is coupled to the receptor.
      • The concentration of permanent ions inside and outside the cell.
Neuromuscular junction

Example of chemical synapse, a neuromuscular junction
ACH: acetylcholine

Image: “Neuromuscular junction” by Doctor Jana. License: CC BY 4.0, edited by Lecturio.
Excitatory and inhibitory synapse examples

Excitatory and inhibitory synapse examples:
Left: excitatory synapse using an excitatory postsynaptic potential (EPSP) and the neurotransmitter glutamate to create a positive depolarization.
Right: inhibitory postsynaptic potential (IPSP) using the neurotransmitter GABA, causing hyperpolarization

Image by Lecturio.

Neurotransmitters

> 500 unique neurotransmitters have been identified in humans. Neurotransmitters are:

  • Proteins stored in the synaptic vesicles
  • Chemical messengers that transmit signals from a neuron to a target cell
  • Clustered close to the cell membrane of the axon terminal
  • Released into the synaptic cleft as a result of a threshold action potential in the presynaptic neuron
  • Either excitatory or inhibitory

Neurotransmitter classes

  • Amino acid:
    • Glutamate
    • Glycine
    • GABA
  • Cholinergic:
    • Acetylcholine
  • Catecholamine:
    • Dopamine
    • Norepinephrine
    • Epinephrine
  • Monoamine:
    • Serotonin
    • Histamine
  • Opioid:
    • Dynorphins
    • Endorphins
    • Enkephalins
  • Soluble gases:
    • NO
    • CO

Common neurotransmitters and their actions

Table: Common neurotransmitters and their actions
NeurotransmitterCharacteristicsSite of synthesis
DopamineExcitatory and inhibitoryCNS: substantia nigra, ventral tegmental area, and others
NorepinephrineExcitatoryCNS: locus coeruleus, sympathetic nervous system, and adrenal medulla
EpinephrineExcitatoryAdrenal medulla
Serotonin
  • Inhibitory
  • Involved in mood, sleep, and pain inhibition
CNS: raphe nuclei and enterochromaffin cells
HistamineExcitatory and inhibitory
  • CNS: histaminergic neurons in the basal ganglia
  • Periphery: mast cells and basophils
AcetylcholineExcitatory (usually)Neuromuscular junctions, presympathetic synapses, and preganglionic sympathetic synapses
Glutamate
  • Principal excitatory neurotransmitter
  • Role in learning and memory
  • Synthesizes GABA
CNS: almost every part of the nervous system
GABA
  • Inhibitory
  • Synthesized from glutamate
  • Principal inhibitory neurotransmitter
CNS
GlycineInhibitoryCNS: spinal cord, brain stem, and retina
EnkephalinsInhibitory (pain)CNS
EndorphinsInhibitoryCNS and PNS
NeurokininsGI tract: modulate motility, fluid, and electrolyte secretionIntrinsic enteric neurons and extrinsic primary afferent nerve fibers
Substance PModulates vasodilation, inflammation, pain, and the process of vomitingIntrinsic enteric neurons and extrinsic primary afferent nerve fibers
Gastrin-releasing peptideStimulates the release of gastrin from the G cellsPostganglionic fibers of the vagus nerve
PNS: peripheral nervous system

Neurotransmission

  1. Vesicles filled with neurotransmitters arrive from cell soma and reside in the presynaptic knob.
  2. Action potential arrives via the axon.
  3. Voltage-gated Ca2+ channels open.
  4. Vesicles are stimulated.
  5. Neurotransmitter vesicles fuse with synaptic membranes and release the neurotransmitter contents in the synaptic cleft.
  6. Postsynaptic receptor binds the transmitter and opens. 
  7. Unbound transmitter is degraded, recycled, or diffused out of the cleft.
Neurotransmission-actions-at-the-synapse

Neurotransmission actions at the synapse

Image by Lecturio.

Clinical Relevance

  • Myasthenia gravis: autoimmune disease characterized by a production of autoantibodies against acetylcholine receptors on the postsynaptic membrane. When these receptors are blocked, muscle contraction is inhibited. Individuals with myasthenia gravis report exhaustion and fatigue as the day ends. The classic early symptom is drooping of the eyelids as nighttime approaches.
  • Parkinson’s disease: neurodegenerative disorder in which the production of dopamine is decreased owing to destruction of the cells producing it in the substantia nigra. This destruction results in symptoms such as tremors, loss of movement control, hypokinesia, rigidity, dementia, and depression.
  • Tetanus toxin: prevents the release of GABA, an inhibitory neurotransmitter. This release results in unchecked excitatory signals to the skeletal muscles, which go into spasm. The jaw muscles are specifically affected, giving the classic sign of lockjaw. As the disease progresses, the respiratory muscles also get involved, causing death.
  • Botulism: Botulinum toxin is among the most toxic proteins known. This toxin is produced by the bacterium Clostridium botulinum. When botulinum toxin binds to the synaptic vesicle proteins and gangliosides, it prevents the release of acetylcholine, a stimulatory neurotransmitter, inhibiting stimulatory effects, preventing muscle contraction, and causing flaccid paralysis.
  • Autism spectrum disorder: neurodevelopmental disorder marked by poor social skills, restricted interests and social interactions, and repetitive and stereotyped behaviors. This condition is termed a “spectrum” because of the wide variability in the severity of symptoms exhibited. Some individuals suffer from severe impairment in language and intellectual levels, while others may have normal or even advanced intellect. 
  • Huntington disease: progressive neurodegenerative disorder with an autosomal dominant mode of inheritance. It is caused by CAG (cytosine-adenine-guanine) trinucleotide repeats in the huntingtin (HTT) gene. A common clinical presentation in adulthood is a movement disorder known as chorea—abrupt, involuntary movements of the face, trunk, and limbs. Management is supportive.
  • Schizophrenia: serious chronic mental health disorder. Schizophrenia is characterized by the presence of psychotic symptoms, disorganized speech or behavior, flat affect, avolition, anhedonia, poor attention, and alogia. Management includes antipsychotics in conjunction with behavioral therapy.
Table: Changes in neurotransmitters in different diseases
DopamineAcetylcholineNorepinephrineSerotoninGABA
Schizophrenia
Anxiety
Depression
Alzheimer disease
Huntington disease
Parkinson’s disease

References

  1. Perea G, Navarrete M, Araque A. (2009). Tripartite synapses: astrocytes process and control synaptic information. Trends in Neurosciences 32:421–431.
  2. Missler M, Südhof TC, Biederer T. (2012). Synaptic cell adhesion. Cold Spring Harb Perspect Biol 4:a005694.
  3. Schacter DL, Gilbert DT, Wegner DM. (2011). Psychology, 2nd ed. New York: Worth, p. 80.
  4. Palay S. (1956). Synapses in the central nervous system. J Biophys Biochem Cytol 2:193–202.
  5. Tansey EM. (1997). Not committing barbarisms: Sherrington and the synapse, 1897. Brain Research Bulletin 44:211–212.
  6. Jones RA, Harrison C, Eaton SL, et al. (2017). Cellular and molecular anatomy of the human neuromuscular junction. Cell Rep 21:2348–2356. 
  7. Harris AL.(2018). Electrical coupling and its channels. J Gen Physiol 150:1606–1639. 
  8. Südhof TC. (2018). Towards an understanding of synapse formation. Neuron 100:276–293. 
  9. Südhof TC. (2012). The presynaptic active zone. Neuron 75:11–25.
  10. Lisman JE, Raghavachari S, Tsien RW. (2007). The sequence of events that underlie quantal transmission at central glutamatergic synapses. Nat Rev Neurosci 8:597–609.

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