Biology 463 - Neurobiology
Topic 5
Synaptic Transmission
Lange
Introduction
Synaptic Transmission
– The synapse is the “space”
between neurons or neurons
and other cells
– Information transfer occurs
from one neuron to the next
at a synapse
– Has a significant role in
EVERY ACTIVITY of the
nervous system
Charles Sherrington – recipient of the 1932 Nobel Prize in
physiology. Dr. Sherrington was a physiologist and originator of
the term “synapse”
Otto Loewi – in the 1920s identified that the message transmission between
the heart and the vagus nerve was chemical. He initially called this
compound “vagussstoff” and it eventually became known as acetylcholine.
Edwin Furshpan (left) and David Potter (right) in the 1950s first
demonstrated electrical synapses. These were first
demonstrated in escape-related giant neurons in crayfish.
Properties of Synapses
In the synapse, there is a specific direction of information flow
– Movement is in one direction: neuron to target cell
– The neuron ahead of the synapse is the presynaptic neuron
– The neuron after the synapse is called the postsynaptic neuron or
sometimes the target neuron
Chemical Synapses – at a chemical synapse, one neuron releases a
neurotransmitter into a small space (the synapse) that is adjacent to another
neuron.
Electrical Synapses - a mechanical and electrically conductive link between
two abutting neurons formed at a narrow gap between the pre- and
postsynaptic neurons known as a gap junction.
• Compared to chemical synapses, electrical synapses
impulses faster, but
conduct nerve
• Unlike chemical synapses electrical synapses do not have “gain” (the
signal in the postsynaptic neuron is the same or smaller than that of the
originating neuron).
• Electrical synapses are often found in neural systems that require the
fastest possible response, such as defensive reflexes.
The gap junction is the key
feature allowing for electrical
synapse firing between neurons.
Note: Because the gap junction is able to allow
ion flow in either direction, the effect is to make
electrical synapses BIDIRECTIONAL. This
difference means that neural circuits with
electrical synapses can perform quite differently
than those with chemical synapses.
Typically the channel created by
the grouping of proteins is called
a connexon. However, as shown
here, the term connexon can also
be applied to the aggregate
cluster of proteins.
Electrical Synapses can occur in places other than in regions associated with
escape behaviors. In this example, electrical synapses are located in the
vertebrate brain and it is now know that the entirety of the CNS contains many
electrical synapses.
It is believed that
the electrical
synapse is
associated with
regions/responses
that require an
especially high
degree of
synchrony.
The Chemical Synapse:
-synaptic cleft
-presynaptic potential
-postsynaptic potential
-secretory granules
(dense core vesicles)
-synaptic vesicles
-receptors
-active zone
Fast Excitatory
Synapse – for
example one of
the class of
nicotinic
neurons in the
brain.
General
Synapse in the
PNS
CNS Synapses
–
–
–
–
Axodendritic: Axon to dendrite
Axosomatic: Axon to cell body
Axoaxonic: Axon to axon
Dendrodendritic: Dendrite to dendrite
• CNS Synapses (Specialized Groupings)
– Gray’s Type I: asymmetrical postsynaptic membrane (thicker)
typically excitatory
– Gray’s Type II: symmetrical postsynaptic membrane
typically inhibitory
Arrow above points to the synapse from
the presynaptic side. Gray's Type 1 is
synonymous with the term Asymmetric
Synapse.
Arrow above points to the synapse
from the presynaptic side.
Gray's Type 2 is synonymous with the
term Symmetric Synapse.
The Neuromuscular Junction (NMJ)
• the post synaptic membrane at a
muscle cell or group
• this post synaptic membrane is called
a motor end plate
THOUGHT QUESTION:
These NMJ’s have been widely studied for
many decades and have been used to
understand general mechanisms of many
neural junctions (aka synapses). Why do
you think this is so?
Steps Seen in Chemical Synaptic Transmission
– Neurotransmitter synthesis
– Loading of neurotransmitter into synaptic vesicles
– Vesicles fuse with SNARE pins to presynaptic terminal
– Neurotransmitter spills into synaptic cleft via exocytosis
– Neurotransmitter binds to postsynaptic receptor proteins
– Biochemical “electrical” message elicited in postsynaptic cell
– Removal/retrieval of neurotransmitter from synaptic cleft
Major Neurotransmitter Groups
Amino acids: small organic molecules that we know are the
building blocks of proteins
• Glutamate - considered to be the major mediator of excitatory
signals in the mammalian central nervous system and is involved in
most aspects of normal brain function including cognition, memory
and learning.
• Glycine - Glycine is an inhibitory neurotransmitter in the
central nervous system, especially in the spinal cord,
brainstem, and retina.
• GABA – (γ-Aminobutyric acid) is the chief inhibitory
neurotransmitter in the mammalian central nervous
system. It plays a role in regulating neuronal excitability
throughout the nervous system. In humans, GABA is also
directly responsible for the regulation of muscle tone.
Amines: organic compounds and functional groups that contain a
basic nitrogen atom with a lone pair. Amines are derivatives of
ammonia.
Dopamine - a catecholamine neurotransmitter present
in a wide variety of animals. In the brain, dopamine is
involved in activating five different types of dopamine
receptors—D1, D2, D3, D4, and D5.
Acetylcholine - in the PNS, acetylcholine activates
muscles, and is a major neurotransmitter in the
autonomic nervous system. In the CNS, acetylcholine
and the associated neurons form a neurotransmitter
system, the cholinergic system, which tends to cause
“anti-excitatory” actions
Histamine - cell bodies of histaminergics, the neurons
which release histamine, are found in the posterior
hypothalamus. Histaminergic action is known to
modulate sleep. Classically, antihistamines (H1
histamine receptor antagonists) produce sleep.
Peptides: Short amino acid chains (i.e. proteins)
stored in and released from secretory granules.
Dynorphin - produced in many different parts of
the brain, including the hypothalamus, and the
spinal cord. Dynorphin has many different
physiological actions, depending upon its site of
production.
•
dynorphin that is made in magnocellular
vasopressin neurons of the supraoptic nucleus is
important in the patterning of electrical activity
•
Dynorphin produced in the arcuate nucleus
and in orexin neurons of the lateral
hypothalamus affects the control of appetite.
Enkephalins - involved in regulating nociception
in the body. The enkephalins are termed
endogenous ligands, or specifically endorphins
Principles of Chemical Synaptic Transmission
Neurotransmitter Release
– Exocytosis: Process by which vesicles release their contents
-
Mechanisms
•Process of exocytosis stimulated by release of intracellular
calcium, [Ca2+]
•Vesicle membrane incorporated into presynaptic membrane
•Neurotransmitter released
•Vesicle membrane recovered by endocytosis
Two Broad Classes of Neural Receptor Types
Ionotropic Receptors - transmitter-gated ion channels containing a protein
channel pore.
Metabotropic Receptors - a subtype of membrane
receptors at the surface or in vesicles of eukaryotic cells.
Principles of Chemical Synaptic Transmission
•
•
•
Excitatory and Inhibitory Postsynaptic Potentials:
EPSP:Transient postsynaptic membrane depolarization by presynaptic
release of neurotransmitter
IPSP: Transient hyperpolarization of postsynaptic membrane potential
caused by presynaptic release of neurotransmitter
• Neurotransmitter Recovery and Degradation
–
–
–
–
Diffusion: Away from the synapse
Reuptake: Neurotransmitter re-enters presynaptic axon terminal
Enzymatic destruction inside terminal cytosol or synaptic cleft
Desensitization: e.g., AChE cleaves Ach to inactive state
• Neuropharmacology
– Effect of drugs on nervous system tissue
– Receptor antagonists: Inhibitors of neurotransmitter receptors
• Curare
– Receptor agonists: Mimic actions of naturally occurring
neurotransmitters
• Nicotine
– Defective neurotransmission: Root cause of neurological and
psychiatric disorders
Principles of Synaptic Integration
Synaptic Integration
– Process by which multiple synaptic potentials combine within one
postsynaptic neuron
Principles of Synaptic Integration
EPSP Summation
– Allows for neurons to perform sophisticated computations
– Integration: EPSPs added together to produce significant postsynaptic
depolarization
– Spatial: EPSP generated simultaneously in different spaces
– Temporal: EPSP generated at same synapse in rapid succession
The Contribution of
Dendritic Properties to
Synaptic Integration
•
•
IPSPs and Shunting Inhibition
– Excitatory vs. inhibitory synapses: Bind different neurotransmitters,
allow different ions to pass through channels
– Membrane potential less negative than -65mV = hyperpolarizing
IPSP
Shunting Inhibition: Inhibiting current flow from soma to axon hillock
• Shunting Inhibition: Inhibiting current flow from soma
to axon hillock
Edgar Douglas Adrian – physiologist who shared
the 1932 Nobel Prize with Sherrington
END.