Excitatory and Inhibitory Inputs to Cells Summate to Produce a Response

Excitatory
Postsynaptic
Potential (EPSP)
Brief depolarization
of a neuron
membrane in
response to
stimulation
Neuron is more
likely to produce an
action are
potential
EPSPs
associated with the
opening of sodium
channels: allows
influx of Na+

Excitatory and Inhibitory Inputs to Cells Summate to Produce a Response

Inhibitory
Postsynaptic
Potential (IPSP)
Brief
hyperpolarization of
a neuron membrane
in response to
stimulation
Neuron is less likely
to produce
an action
IPSPs
are typically
potential with the
associated
opening of potassium
channels (allows an
efflux of K+)
or chloride channels
-

Temporal and Spatial Summation of Synaptic Inputs

A: Imagine a postsynaptic cell receiving two
excitatory inputs from two sensory neurons.
B: Temporal summation:
SN1 fires AP, leads to EPSP in MN. Since
depolarization is small, reaching threshold for
AP generation in MN is unlikely.

If SN1 fires and then fires again before

the EPSP generated by it declines to baseline (dotte
line), the EPSP magnitudes will sum to generate a
larger EPSP. This larger response would be more
likely to reach threshold for an AP in the MN.

C: Spatial summation: If either SN1 or SN2 fires alon

neither EPSP brings the MN to threshold for
AP generation.
But if SN2 fires at the same time
as SN1 a larger EPSP would be generated
bringing the MN closer to threshold for an AP.

Temporal
summationtwo (or
more) inputs at
THE SAME LOCATION
but at DIFFERENT
TIMES
Spatial summation
two (or more) inputs at
DIFFERENT LOCATIONS
but at the SAME TIME

If the summated EPSPs and

IPSPs on the dendritic tree and
cell body result in the membrane
in the axon hillock reaching
threshold, an action potential is
generated and travels down the
axon membrane in an all-or-none
fashion.

Example of the use of inhibition in the

control of neuronal activitymouse
spinal cord (also in humans).
Main axon of motor neuron projects to muscle.
Axon collateral remains in spinal cord & synapses
with Renshaw inhibitory interneuron.
Motor axon and collateral both release acetylcholine.
When the motor neuron is highly excited, it can
modulate its activity level through the Renshaw loop.
Inhibitory interneuron suppresses activity of motor
neuron. (See plus and minus signs.)
Puts on the brakes when over-excited.
Strychnine (rat poison) blocks inhibitory
neurotransmitterleads to over excitation and death.

Neurotransmission in Four Steps

The neurotransmitter must

1. Be synthesized, moved to,
and stored in the axon
terminal.
2. Be released in response to
an action potential.
3. Activate receptors on the
target cell located on the
postsynaptic membrane.
4. Be inactivated, or it will
continue to work indefinitely.

4 Criteria for Identifying Neurotransmitters

1.
2.

3.

4.

The chemical must be synthesized

in the neuron or otherwise be
present in it.
When the neuron is active, the
chemical must be released and
produce a response in some
target.
The same response must be
obtained when the chemical is
experimentally placed on the
target.
A mechanism must exist for
removing the chemical from its site
of action after its work is done.

The evidence that chemical neurotransmitters are released from nerve terminals
and affect target cells.

Some soluble chemical being released by the Vagus nerve was controlling the heart rate.
Not a direct connection between the nerve and the heart. The chemical is acetylcholine.

Epinephrine (EP, or adrenaline)

Chemical messenger that acts as a hormone to

mobilize the body for fight or flight during times of
stress.

(Parasympathetic
Nervous System)
Acetylcholine

(Sympathetic
Nervous System)
Epinephrine

Chemicals relay excitatory messages to say speed up and inhibitory

messages to say slow down.

Acetylcholine

The first neurotransmitter discovered in the PNS

slows the heartbeat via the Vagus nerve and is thus
inhibitory.

Is also the transmitter that is released from

motor neurons.
causes muscles to contract and is thus excitatory.

Ionotropic
receptors are
fastquickly
change shape
and open or
close an ion
channel when
the transmitter
molecule binds.

Metabotropic
receptors are
slowwhen
activated
they alter
chemical
reactions in
the cell,
using a
system of
second
messengers,
to open an
ion channel.

Neurotransmitter Systems Form a Complex Array in the Brain

Loss of these neurons is

associated with
Alzheimers disease, andImportant for motor
disruption of pathways controloriginate in the
interferes with learning substantia nigra of the
midbrain. Parkinsons
and memory.
disease is a result of
loss of these neurons.

Controls
many
behaviors
ranging from
alertness to
mood to
sexual

Important for
many
aspects of
behavior
such as
mood,
anxiety, and

Types of neurotransmitters:
Amine neurotransmittersacetylcholine, dopamine,
serotonin.
Amino acid neurotransmittersGABA, glutamate.
Peptide neurotransmitters, or neuropeptides
oxytocin, vasopressin.
Gas neurotransmittersnitric oxide, carbon
monoxide.

Drugs Fit Like Keys into Molecular Locks

A ligand is a substance that binds to a receptor.
When a neurotransmitteran endogenous ligand
binds a receptor it activates a change such as opening
an ion channel.
When an exogenous ligand such as a drug binds it
may activate the receptor, acting as an agonist.
Other ligands bind and block the receptor but do not
activate itantagonists (or receptor blockers) prevent
the normal transmitter from binding.

The Agonistic and Antagonistic Actions of Drugs

The effects of a drug depend on where it binds and what it

does.
The binding affinity (or affinity) is the degree of
chemical attraction between a ligand and a receptor.
The efficacy (or intrinsic activity) is the ability of a
bound ligand to activate the receptor.
A dose-response curve (DRC) is a graph of the
relationship between drug doses and the effects.

The Dose-Response Curve

Presynaptic
Tetrodotoxin
(Puffer fish)
Saxitoxin
(Dinoflagellate
algal blooms or red tide)
paralytic shellfish
poisoning from eating
mussels, clams who
have eaten the
dinoflagellates
Block voltage-gated
Na+ channels, and thus
AP propagation
Diaphragm muscle fails
to contractsuffocation
ensues.

Neurotoxins and Drugs

Presynaptic
Tetrodotoxin
(Puffer fish)
Saxitoxin
(Dinoflagellate)
Charybdotoxin
(Scorpion venom)
Acts by blocking a
K+ channel.
Broaden the AP and
increase the duration of
Ca2+ influx.
This leads to
overstimulation,
convulsions and death.

Neurotoxins and Drugs

Presynaptic

Neurotoxins and Drugs

Tetrodotoxin
(Puffer fish)
Saxitoxin
(Dinoflagellate)
Charybdotoxin
(Scorpion)
Agatoxin
(Funnel-web spider)
Conotoxin
(Cone snail)
Used to capture prey.
The mechanism of
action of these
is to block Ca2+
channels at the
nerve terminal
--this effectively decouples synapses and can lead to paralysis.

Presynaptic

Neurotoxins and Drugs

Tetrodotoxin
(Puffer fish)
Saxitoxin
(Dinoflagellate)
Charybdotoxin
(Scorpion)
Agatoxin
(Funnel-web spider)
Conotoxin
(Cone snail)
Botulinum Toxin
(Botox)
Tetanus Toxin
(bacteria)
These clostridial toxins
act by cleaving the
proteins important for
fusing the presynaptic
vesicles with the presynaptic membrane.

Presynaptic

Neurotoxins and Drugs

Tetrodotoxin
(Puffer fish)
Saxitoxin
(Dinoflagellate)
Charybdotoxin
(Scorpion)
Agatoxin
(Funnel-web spider)
Conotoxin
(Cone snail)
Botulinum Toxin
Tetanus Toxin
(bacteria)
Latrotoxin
(Black Widow Spider)
Causes massive transmitter release (and thus depletion of
neurotransmitter). by somehow bypassing the Ca 2+
dependence of release. It causes transmitter release in the
absence of electrical stimulation and Ca 2+ influx through Ca2+
channels.

Presynaptic

Neurotoxins and Drugs

Tetrodotoxin
(Puffer fish)
Saxitoxin
(Dinoflagellate)
Charybdotoxin
(Scorpion)
Agatoxin
(Funnel-web spider)
Conotoxin
(Cone snail)
Botulinum Toxin
Tetanus Toxin
(bacteria)
Latrotoxin
(Black Widow Spider)

Caffeine

Inhibits autoreceptors normally activated by adenosine (a

break-down product of ATP released with ACh. These
autoreceptors normally inhibit the activity of the presynaptic
terminal.

Presynaptic
Tetrodotoxin
(Puffer fish)
Saxitoxin
(Dinoflagellate)
Charybdotoxin
(Scorpion)
Agatoxin
(Funnel-web spider)
Conotoxin
(Cone snail)
Botulinum Toxin
Tetanus Toxin
(bacteria)
Latrotoxin
(Black Widow Spider)

Caffeine

Neurotoxins and Drugs

Postsynaptic

Curare (plant toxin)

Cobratoxin
(Cobra snake)
Alpha bungarotoxin
(Krait snake)
Act by binding to the
acetylcholine receptors on
muscle membrane to
prevent the naturally
occurring transmitter from
binding. This leads to
paralysis and, eventually,
death.

Presynaptic
Tetrodotoxin
(Puffer fish)
Saxitoxin
(Dinoflagellate)
Charybdotoxin
(Scorpion)
Agatoxin
(Funnel-web spider)
Conotoxin
(Cone snail)
Botulinum Toxin
Tetanus Toxin
(bacteria)
Latrotoxin
(Black Widow Spider)

Caffeine

Neurotoxins

Postsynaptic
Curare (plant toxin)
Cobratoxin
(Cobra snake)
Alpha bungarotoxin
(Krait snake)
Cocaine,
amphetamines and
antidepressants
inhibit re-uptake of
transmitter,
prolonging
their effects.

Presynaptic

Neurotoxins and Drugs

Tetrodotoxin
(Puffer fish)
Saxitoxin
(Dinoflagellate)

Curare,
Cobratoxin
(Cobra snake)
Alpha bungarotoxin
(Krait snake)
Cocaine,
amphetamines
and
antidepressants

Charybdotoxin
(Scorpion)
Agatoxin
(Funnel-web spider)
Conotoxin
(Cone snail)

Nerve gas Sarin

(used by terrorists in the
Japanese subway system
In 1995)

Botulinum Toxin
Tetanus Toxin
(bacteria)

Organophosphate
insecticides

Latrotoxin
(Black Widow Spider)

Caffeine

Postsynaptic

If you look at an insect after it has been sprayed with

an insecticide, you may notice that it is twitching
uncontrollably.

Act by blocking AChE the

enzyme that breaks down
ACh to limit the duration of
its action.
Result is overstimulation
and asphyxia.

Presynaptic
Tetrodotoxin
(Puffer fish)
Saxitoxin
(Dinoflagellate)
Charybdotoxin
(Scorpion)
Agatoxin
(Funnel-web spider)
Conotoxin
(Cone snail)
Botulinum Toxin
Tetanus Toxin
(bacteria)
Latrotoxin
(Black Widow Spider)

Caffeine

Neurotoxins and Drugs

Postsynaptic
Curare,
Cobratoxin
(Cobra snake)
Alpha bungarotoxin
(Krait snake)
Cocaine,
amphetamines
and
antidepressants
Nerve gas Sarin
Organophosphate
insecticides

LSD, Ecstasy,
Morphine, Heroin,
Marijuana,
act as agonists at
postsynaptic receptors
Alcohol stimulates
inhibitory synapses.