Transcript week4am

CHAPTER 3
The Neuron,
Synaptic Transmission, Neurotransmitters
and the CNS
a
b
c
Need to think about this question 2 ways
1. within neurons –
2. between neurons-
Neuron receiving info
Information traveling
down neuron

within neurons – electrically

between neurons – chemically
◦ Synapse – space between neurons

the “resting” state

the “active” state
◦ neuron is firing
◦ action potential

the “refractory” state

inside of the axon has a slightly negative
charge relative to outside the axon
◦ called the membrane potential
◦ usually around -70mV

inside of the axon has a slightly negative
charge relative to outside the axon
◦ called the membrane potential

why?
action potential or
spike

see depolarization (change from negative
inside neuron to more positive)
action potential or
spike

see depolarization (change from negative
inside neuron to more positive)
◦ “threshold” – if a great enough depolarization
occurs, an action potential will occur
◦ action potential – very quick – milliseconds
 Other terms – spike, firing, generating an AP
action potential or
spike

Hyperpolarization
 return to negative
 this is the refractory or recovery period
action potential or
spike

All axons and cells have a membrane
 thin lipid (fat) bilayer



The membranes have channels (to allow ions
in or out)
Ions – molecules with a charge
These channels can be open or shut


Ions flowing across the membrane causes the
changes in the potential
Ions are molecules that contain a positive or
negative charge
 anion – negative charge
 cation – positive charge

Na+
sodium
◦ HIGHER CONCENTRATION OUTSIDE THE AXON

Cl-
chloride
◦ HIGHER CONCENTRATION OUTSIDE AXON

K+
potassium
◦ higher concentration inside the axon

Aanions -large (-) molecules
with a negative charge (stuck inside the
axon)

concentration gradient –
◦ ions diffuse from higher concentration to lower
concentration
example of concentration forces
Concentration
Gradient
Na+
Na+ would
enter axon
K+
K+ would
leave axon
Cl-
Cl- would
enter axon

concentration gradient –
◦ ions diffuse from higher concentration to lower
concentration

electrical gradient ◦ opposite charges attract so ions are attracted to an
environment that has a charge that is opposite of
the charge they carry!
example of electrostatic forces
Electrical
Gradient
Na+
go in
K+
stay in
Cl-
stay out
Concentration
Gradient
Electrical
Gradient
Na+
go in
go in
K+
go out
stay in
Cl-
go in
stay out

opening of Na+ channels and influx of Na+
ions

lidocaine,
novocaine, cocaine

TTX – tetrototoxin

Sagitoxin◦ red tides
Concentration
Gradient
Na+
go in
K+
go out
Cl-
go in
Electrical
Gradient
as cell is depolarized (+ intracellular)
nodes of ranvier
nodes of ranvier
What about communication between
neurons?

presynaptic ending –
◦ portion of the axon conveying information to the
next neuron


presynaptic ending –
◦ the portion of the axon that is conveying
information to the next neuron
synapse or synaptic cleft
◦ the space between neurons where communication
occurs



presynaptic ending –
◦ the portion of the axon that is conveying
information to the next neuron
synapse or synaptic cleft
◦ the space between neurons where communication
occurs
postsynaptic membrane
◦ the portion of the neuron (usually dendrite) that
receives information




presynaptic ending –
◦ the portion of the axon that is conveying information to the
next neuron
synapse or synaptic cleft
◦ the space between neurons where communication occurs
postsynaptic membrane
◦ the portion of the neuron (usually dendrite) that receives
information
pre and postsynaptic receptors
◦ proteins in both the presynaptic and postsynaptic
ending that allow for information to be transferred


synaptic vesicles --small enclosed
membranes that contain neurotransmitter found in presynaptic ending
neurotransmitter – substance in vesicles that
are released in synapse and convey info to
the next neuron
synapse


AP reaches presynaptic endingCa+2 channels in presynaptic ending open
and Ca+2 enters
Why are Ca+2 ions important?
Ca+2 entry into the presynaptic ending
critical for neurotransmitter release
Figure 3.5 A. Photomicrograph of a synapse in action, taken with
the electron microscope. B. Schematic of the process
Julien: A Primer of Drug Action, Eleventh Edition
Copyright © 2008 by Worth Publishers


protein embedded in membrane
mechanism for neurotransmitter to influence
postsynaptic activity by binding to receptor

NT binds to postsynaptic receptors and
causes small local changes in electrical
potential (depolarizations or
hyperpolarizations)◦ Called graded potentials
Graded Potentials-

◦
increase or decrease the likelihood of the neuron
receiving info to generate an action potential

graded potentials that increase the likelihood
of an action potential are called EPSPs
(excitatory postsynaptic potentials)


graded potentials that increase the likelihood
of an action potential are called EPSPs
(excitatory postsynaptic potentials)
graded potentials that decrease the likelihood
of an action potential are called IPSPs
(inhibitory postsynaptic potentials)

NT binding to postsynaptic receptors cause
local ion channels to open


– chemically dependent ion channels
in contrast with electrically dependent ion
channels

postsynaptic receptors open ion channels –
◦ ion channels in postsynaptic membrane (that we
need to worry about) include Na+, Cl- and K+

EPSPs – excitatory postsynaptic potentials
 - increase the likelihood of an AP
 - opening of

EPSPs – excitatory postsynaptic potentials
 opening of local Na+ channels
 IPSPs
– inhibitory postsynaptic
potentials
◦ IPSPs – inhibitory postsynaptic
potentials
• decreases the liklihood of an action potential
 opening of
◦ graded potentials are summed at
axon hillock
Axon hillock
◦ EPSPs and IPSPs are summed a
axon hillock……..AND
Graded potentials are localized – has
impact in limited region; AP travels
down the axon
Neurotransmitters and Receptors
General Principles
• Synthesis
1. Formation of
transmitters
2. Precursors are the
main ingredient.
• Brought to the neuron
by the bloodstream.
• Taken up by cell body
and/or terminal.
• Often come from
substances in the diet.
3. Enzymes put the
ingredients together.
Neurotransmitters and Receptors
Transmitters Stored
in Vesicles
1. Concentration
2. Protection
Neurotransmitters and Receptors
Release =
exocytosis
– Vesicles fuse with
presynaptic
membrane and
release transmitters
into the synapse.
Binding =
attachment of
transmitter to
receptor
Neurotransmitters and Receptors
There are different
varieties of
receptors.
– Some respond fast
– Called Ionotropic
– Direct reaction to
the transmitter
Neurotransmitters and Receptors
Different varieties of
receptors:
– Other types of
receptors respond more
slowly.
– Indirectly
– Called Metabotropic, or
G protein-coupled
– Initiates a second signal
(messenger) inside the
neuron.
Neurotransmitters and Receptors
Inactivation:
Termination of
Synaptic
Transmission
1. Metabolism
2. Re-uptake
3. Re-uptake by glial
cell (glutamate only)
Neurotransmitters
• Acetylcholine
• Catecholamines
– norepinephrine
– dopamine
• Indoleamines
– serotonin
• amino acids
– gaba
– glutamate
• peptides
– opiates
• biogenic amines
– histamine
Neurotransmitters and Receptors
Acetylcholine—first to be recognized,
because of peripheral actions
• Synthesis
– Acetyl-CoA (in mitochondria) + choline (from diet)
Published in 1939
Neurotransmitters and Receptors
Inactivation:
– Acetylcholinesterase (AChE)
– After action in postsynaptic cleft, AChE degrades
ACh to choline and acetate, which are taken back
up into the neuron.
Neurotransmitters and Receptors
Where is ACh produced?
• Septal nucleus and
nucleus basalis
– Projects to
forebrain.
• Midbrain
– Projects to reticular
formation, pons,
cerebellum, and
cranial nerve nuclei.
Ach
Ach
NE
Ach
Ach
Cholinergic system
Neurotransmitters and Receptors
• Receptors
– Nicotinic
– Muscarinic
• AChE Inhibitors
– Irreversible
• Often toxic
• Include pesticides and
nerves gases
– Reversible
• Cognitive enhancers
• Treating Alzheimer’s
Neurotransmitters and Receptors
Catecholamines
• Synthesis
– Tyrosine
• Dopamine
– Norepinephrine
• Termination
– Re-uptake
– Monoamine oxidase
(MAO)
Neurotransmitters and Receptors
• DA Pathways
– 3 classic circuits
• Hypothalamus to pituitary gland
– tuberofundibular; hormonal
• Substantia nigra to basal ganglia
– nigrostriatal pathway - movement
• VTA to cortex and limbic system
– mesolimbic
– mesocortical
– mesolimbicortical
DA Pathways
Neurotransmitters and Receptors: DA
Neurotransmitters and
Receptors
• Receptors
– Dopamine
• Two families:
D1 and D2
• D1 – D5