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Neural Zones

Figure 5.2

How Neurons connect

The Synapse
A functional connection between surfaces
Signal transmission zone
Synapse synaptic cleft, presynaptic cell, and
postsynaptic cell
Synaptic cleft space in between the presynaptic and
postsynaptic cell
Postsynaptic cell neurons, muscles, and endocrine
Neuromuscular junction synapse between a motor
neuron and a muscle

The Synapse
Axon terminal: found in motor neurons
Axon varicosities: ie swellings. Arranged like beads on a string and
contain neurotransmitter containing vesicles
En passant synapse: CNS. Consists of a swelling along the axon
Spine synapse: presynaptic cell connects with a dendritic spine on
the dendrite of the postsynaptic cell

The Synapse
Axodentritic: between axon terminal of one neuron and the dendrite
of another
Axosomatic: between the axon terminal of one neuron and the cell
body of another
Dendrodendritic: between dendrites of neurons (often are electricla
Axoaxonic: between an axon terminal of a presynatpic neuron and
the axon of a postsynaptic neuron.


Diversity of Signal Conduction

So far:

Action potentials
Saltatory conduction
Chemical and electrical synapses

Diversity of Synaptic Transmission

Figure 5.26

Electrical and Chemical Synapses

Electrical synapse

Chemical synapse

Rare in complex animals Common in complex

Common in simple

Rare in simple animals





Postsynaptic signal is
similar to presynaptic

Postsynaptic signal can

be different


Excitatory or inhibitory

Electrical synapses
cells connect via gap junctions
- membranes are separated by 2 nm
- gap junctions link the cytosol of two cells
- provide a passageway for movement of very
small molecules and ions between the cells
- gap junction channels have a large conductance
- NO synaptic delay (current spread from cell to cell is instantaneous)
- important in some reflexes
- chemical synapses do have a significant delay ie slow
- commonly found in other cell types as well i.e. glia
- can be modulated by intracellular Ca2+ , pH, membrane voltage,
- clusters of proteins that span the gap such that ions and small
molecules can pass directly from one cell to another

More about electrical synapses

cells connect via gap junctions
- made up of 6 protein subunits arranged around a central pore, made
up of the connexin protein
- the two sides come together to make a complete unit of 12 proteins
around the central pore

Chemical Synapse Diversity

Vary in structure and location

Figure 5.27

Chemical Synapse
most common type of synapse
electrical signal in the presynaptic cell is communicated to the
postsynaptic cell by a chemical (the neurotransmitter)
separation between presynaptic and postsynaptic membranes is
about 20 to 30 nm
a chemical transmitter is released and diffuses to bind to receptors
on postsynaptic side
bind leads (directly or indirectly) to changes in the postsynaptic
membrane potential (usually by opening or closing transmitter
sensitive ion channels)
the response of the neurotransmitter receptor can depolarizes
(excitatory postsynaptic potential; epsp) or hyperpolarizes (inhibitory
postsynaptic potential; ipsp) the post-synaptic cell and changes its
significant delay in signal (1 msec) but far more flexible than
electrical synapse

More about chemical Synapses

Some types of chemical synapse include

Excitatory - excite (depolarize the postsynaptic cell
Inhibitory - inhibit (hyperpolarize the postsynaptic cell)
Modulatory - modulates the postsynaptic cells response to other

General sequence of events


* *

General sequence of events

1. Nerve impulse arrives at presynaptic terminal
2. Depolarization causes voltage-gated Ca 2+ channels to open
- increases Ca 2+ influx, get a transient elevation of internal Ca 2+
~100 mM
3. Vesicle exocytosis
- increase in Ca 2+ induces fusion of synaptic vesicles to membrane
- vesicles contain neurotransmitters
4. Vesicle fusion to membrane releases stored neurotransmitter
5. Transmitter diffuses across cleft to postsynaptic side
6. Neurotransmitters bind to receptor either:
i) ligand-gated ion channel or
ii) receptors linked to 2nd messenger systems
7. Binding results in a conductance change
- channels open or close or
- binding results in modulation of postsynaptic side

General sequence of events

8. Postsynaptic response
- change in membrane potential (e.g. muscle contraction in the case
of a motorneuron at a neuromuscular junction)
9. Neurotransmitter is removed from the cleft by two mechanisms
i) transmitter is destroyed by an enzyme such as acetylcholine
ii) transmitter is taken back up into the presynaptic cell and recycled
e.g. - acetylcholine esterase, breaks down acetylcholine in cleft,
choline is recycled back into the presynaptic terminal

Synthesized in neurons
Released at the presynaptic cell following
Bind to a postsynaptic receptor and causes an

Neurotransmitters, Cont.
More than 50 known substances

Amino acids
Biogenic amines
Miscellaneous ..

Neurons can synthesize many kinds of



Neurotransmitters cont.

Signal Strength
Influenced by neurotransmitter amount and
receptor activity
Neurotransmitter amount: Rate of release
vs. rate of removal
Release: due to frequency of APs
Passive diffusion out of synapse
Degradation by synaptic enzymes
Uptake by surrounding cells

Receptor activity: density of receptors on

postsynaptic cell

Graded Potentials via Neurotransmitters

Vary in magnitude depending on the
strength of the stimulus
e.g., more neurotransmitter more ion
channels will open
Can depolarize (Na+ and Ca2+ channels) or
hyperpolarize (K+ and Cl- channels) the cell

Graded Potentials

Figure 5.4

Graded Potentials Travel Short Distances

Figure 5.6

Neurotransmitter Receptor Function

Ligand-gated ion channels
e.g., nicotinic ACh

Channel changes shape
Signal transmitted via
secondary messenger
Ultimately sends signal to
an ion channel
Long-term changes
Figure 5.28

Second Messenger again

When activated by a ligand the catalytic
domain starts a phosphorylation cascade
Named based on the reaction catalyzed

Second Messengers to know

Neurotransmitter receptors
Different types of neurotransmitter receptors
Functional Type Ligand Ion Channel
Excitatory Receptors
Glutamate Na+/K+; Ca2+
Serotonin Na+/K+
Inhibitory Receptors
Glycine Cl-


Aminobutyric acid, GABA


Amount of Neurotransmitter
Influenced by AP frequency which influences
Ca2+ concentration
Control of [Ca2+]

Open voltage-gated Ca2+ channels [Ca2+]

Binding with intracellular buffers [Ca2+]
Ca2+ ATPases [Ca2+]

High AP frequency influx is greater than

removal high [Ca2+] many synaptic
vesicles release their contents high

Removal of Neurotransmitter

broken down by enzyme

- acetylcholine esterase breaks down acetylcholine in the
synaptic cleft
- many nerve gases and insecticides work by blocking
acetylcholine esterase Yikes!
- prolongs synaptic communication


recycled by uptake
- most neurotransmitters are removed by Na+/neurotransmitter
- due to a specific neurotransmitter transporter
- recycled by uptake into presynaptic terminal or other cells
(glial cells will take up neurotransmitters)


diffusion: simple diffusion away from site

Neurotransmitters - stages

- all small chemical neurotransmitters are made in the nerve
- responsible for fast synaptic signalling
- synthetic enzymes + precursors transported into nerve terminal
- subject to feedback inhibition (from recycled neurotransmitters
- can be stimulated to increase activity (via Ca2+ stimulated


Packaging into vesicles

- neurotransmitters packaged into vesicles
- packaged in small "classical" vesicles
- involves a pump powered by a pH gradient between outside and
inside of vesicle
- pump blocked by drugs and these block neurotransmitter

Presynaptic vesicles
Two groups
i) low molecular weight, non-peptide
e.g. acetylcholine, glycine, glutamate
ii) neuropeptide (over 40 identified so far and counting..)

Presynaptic vesicles
There are 2 types of secretory vesicles
We will only talk about small chemical synaptic vesicles
Neuropeptides are made and packaged in the cell body and
transported to synapse)
Small chemical neurotransmitter vesicles
responsible for fast synaptic signaling
store non-peptide neurotransmitters,
e.g. acetylcholine, glycine, glutamate
enough vesicles in the typical nerve terminal to transmit a few
thousand impulses
exocytosis only occurs after an increase of internal Ca 2+ (due to
depolarization) and at active zones (regions in the presynaptic
membrane adjacent to the cleft)

Presynaptic vesicles




Vesicle Exocytosis

A group of 6 to 7 proteins work together to respond to Ca 2+ influx

and regulate vesicle fusion
after exocytosis the synaptic vesicle membranes are
reinternalized by endocytosis and reused (reloaded with
neurotransmitter by a transmitter transporter system)
vesicles are also transported from the cell body to the nerve
- transmitter is synthesized in the terminal and loaded into the
- enzymes and substrates necessary are present in the terminal
- i.e. acetylcholine, acetyl-CoA + choline used by choline

Vesicle Exocytosis
non-peptide transmitters

exocytosis only occurs after an increase of internal Ca 2+ (due to


at active zones (regions in the presynaptic membrane adjacent to

the synaptic cleft)
peptide-transmitters (same as for non-peptide transmitters except:)

exocytosis is NOT restricted to active zones

exocytosis is triggered by trains of action potentials

SNARE hypothesis
The SNARE Hypothesis for Transport Vesicle Targeting and Fusion
SNARE is an acronym for SNAP receptor (SNAP stands for soluble Nethylmaleimide-sensitive factor attachment proteins).
SNARES are involved in the mediation of protein transport between
various plant organelles by small membrane vesicles.
Two families:
i) V-SNARE - vesicle membrane proteins
ii) T-SNARE - target membrane proteins

SNARE hypothesis
1. Vesicle docking occurs between the VSNARE and T-SNARE proteins
2. The combined proteins act as a receptor for
an ATPase that utilizes ATP to generate the
"docked" form
3. One of the proteins is a Ca2+ sensor such
that when Ca2+ enters the synapse the
vesicle fuses with the plasma membrane and
releases its contents
4. The membrane and proteins are then
recycled through endocytosis (clatharin coat
and dynamin etc.) and reused.

Primary neurotransmitter at the vertebrate
neuromuscular junction

Figure 5.17

Synaptic Plasticity
Change in synaptic function in response to patterns of
Synaptic facilitation APs neurotransmitter
Synaptic depression APs neurotransmitter
Post-tetanic potentiation (PTP) after a train of high
frequency APs neurotransmitter release

Figure 5.32

Long-term potentiation

Postsynaptic Cells
Have specific receptors for specific
e.g., Nicotinic ACh receptors

Diversity of Signal Conduction

So far:

Action potentials
Saltatory conduction
Chemical and electrical synapses

Shape and speed of action potential
Due to diversity of Na+ and K+ channels

Ion Channel Isoforms

Multiple isoforms
Encoded by many genes
Variants of the same protein
Voltage-gated K+ channels are highly diverse (18 genes
encode for 50 isoforms in mammals)
Na+ channels are less diverse (11 isoforms in mammals)

Table 5.2

Channel Density
Higher density of voltage-gated Na+
Lower threshold
Shorter relative refractory period

Voltage-Gated Ca2+ Channels

Open at the same time or instead of
voltage-gated Na+ channels
Ca2+ enters the cell causing a depolarization
Ca2+ influx is slower and more sustained
Slower rate of APs due to a longer
refractory period
Critical to the functioning of cardiac muscle