Chapter 4
Neural Conduction and
Synaptic Transmission
How Neurons Send and Receive
Signals
1
2
Resting Membrane Potential

Recording the membrane potential:
difference in electrical charge between
inside and outside of cell

Inside of the neuron is negative with respect
to the outside

Resting membrane potential is about –70mV

Membrane is polarized (carries a charge)
3
1
Ionic Basis of the Resting
Potential

Factors contributing to even distribution of
ions (charged particles)



Random motion – particles tend to move down
their concentration gradient
Electrostatic pressure – like repels like,
opposites attract
Factors contributing to uneven distribution of
ions


Selective permeability to certain ions
Sodium-potassium pumps
4
Ions Contributing to Resting
Potential

Sodium (Na+)

Chloride (Cl-)

Potassium (K+)

Negatively charged proteins (A-)

Synthesized within the neuron

Found primarily within the neuron
5
The Neuron in its Resting State
6
2
The Neuron at Rest

Ions move in and out through ion-specific
channels

K+ and Cl- pass readily

Little movement of Na+

A- don’t move at all, trapped inside
7
The Neuron at Rest
Continued
Equilibrium Potential (Hodgkin-Huxley model)

The potential at which there is no net movement
of an ion – the potential it will move to achieve
when allowed to move freely

Na+ = 120mV

K+ = 90mV

Cl- = -70mV (same as resting potential)
8
The Neuron at Rest
Continued

Na+ is driven in by both electrostatic
forces and its concentration gradient

K+ is driven in by electrostatic forces and
out by its concentration gradient

Cl- is at equilibrium

Sodium-potassium pump – active (uses
ATP) force that exchanges 3 Na+ inside for
2 K+ outside
9
3
10
FIGURE 4.2 The passive and active
factors that influence the distribution
of Na+, K+, and Cl- ions across the
neural membrane.
11
Generation and Conduction of
Postsynaptic Potentials (PSPs)

Neurotransmitters bind at postsynaptic
receptors

These chemical messengers bind and cause
electrical changes

Depolarizations (making the membrane potential
less negative)

Hyperpolarizations (making the membrane
potential more negative)
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4
FIGURE 4.3 An EPSP, and IPSP, and an
EPSP followed by a typical AP.
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EPSPs and IPSPs

Travel passively from their site of
origination

Decremental (graded) – they get smaller
as they travel
14
Integration of PSPs and
Generation of Action Potentials
(APs)



One EPSP typically will not suffice to cause a
neuron to “fire” and release neurotransmitter –
summation is needed
In order to generate an AP (or “fire”), the threshold
of activation must be reached near the axon
hillock
Integration of IPSPs and EPSPs must result in a
potential of about -65mV in order to generate an
AP
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5
Integration

Adding or combining a number of
individual signals into one overall signal

Spatial summation – integration of events
happening at different places

Temporal summation – integration of
events happening at different times
16
FIGURE 4.4 The three possible
combinations of spatial summation.
FIGURE 4.5 The two possible
combinations of temporal summation.
17
Conduction of APs

All-or-none – when threshold is reached
the neuron “fires” and the action potential
either occurs or it does not

When threshold is reached, voltageactivated ion channels are opened
18
6
FIGURE 4.6 The opening and closing of voltageactivated sodium and potassium channels during the
three phases of the action potential: rising phase,
repolarization, and hyperpolarization.
19
Refractory Periods

Absolute – impossible to initiate another
action potential

Relative – harder to initiate another action
potential

Prevent the backwards movement of APs
and limit the rate of firing
20
PSPs vs. Action Potentials
(APs)
EPSPs/IPSPs
  Decremental
  Fast
  Passive (energy is
not used)
Action Potentials
  Nondecremental
  Conducted more
slowly than PSPs
  Passive and active
(use ATP)
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7
Signals Conducted Orthodromically thru
Typical Multipolar Neuron
22
Axonal Conduction of APs

Passive conduction (instant and
decremental) along each myelin segment
to next node of Ranvier

New action potential generated at each
node

In myelinated axons: instant conduction
along myelin segments results in faster
conduction than in unmyelinated axons
23
Velocity of Axonal Conduction

Maximum velocity of conduction in human
motor neurons is about 60 meters per
second
24
8
Conduction in Neurons
without Axons

Conduction in interneurons is typically
passive and decremental
25
The Hodgkin-Huxley Model in
Perspective

This model was based on squid motor
neurons

Cerebral neurons behave in ways that are
not always predicted by the model
26
Synaptic Transmission:
Structure of Synapses

Axodendritic are most common; axons
synapse onto dendritic spines

Directed synapse: site of release and
contact are in close proximity

Nondirected synapse: site of release and
contact are separated by some distance
27
9
FIGURE 4.8 The anatomy of the typical
synapse.
28
Synthesis, Packaging, and
Transport of Neurotransmitter
Molecules

Neurotransmitter molecules

Small


Synthesized in the terminal button and packaged
in synaptic vesicles
Large

Assembled in the cell body, packaged in vesicles,
and then transported to the axon terminal
29
Release of Neurotransmitter
(NT) Molecules

Exocytosis – the process of NT release

The arrival of an AP at the terminal opens
voltage-activated Ca2+ channels

The entry of Ca2+ causes vesicles to fuse
with the terminal membrane and release
their contents
30
10
FIGURE 4.11 Schematic and
photographic illustrations of
exocytosis.
31
Activation of Receptors by NT
Molecules

Released NT molecules produce signals in
postsynaptic neurons by binding to
receptors

Receptors are specific for a given NT

Ligand – a molecule that binds to another

A NT is a ligand of its receptor
32
Receptors

There are multiple receptor types for
a given NT

Ionotropic receptors – associated
with ligand-activated ion channels

Metabotropic receptors – associated
with signal proteins and G proteins
33
11
Ionotropic Receptors

NT binds and an associated ion channel
opens or closes, causing a PSP

If Na+ channels are opened, for example,
an EPSP occurs

If K+ channels are opened, for example, an
IPSP occurs
34
Ionotropic receptor
FIGURE 4.12 Ionotropic receptor.
35
Metabotropic Receptors

Effects are slower, longer-lasting, more
diffuse, and more varied

(1) NT 1st messenger binds. (2) G protein
subunit breaks away. (3) Ion channel
opened/closed OR a 2nd messenger is
synthesized. (3) 2nd messengers may have a
wide variety of effects.
36
12
Metabotropic Receptors
37
FIGURE 4.12 Ionotropic and
metabotropic receptors.
38
Reuptake, Enzymatic
Degradation, and Recycling

As long as NT is in the synapse, it is
“active” – activity must somehow be
turned off

Reuptake – scoop up and recycle
NT

Enzymatic degradation – a NT is
broken down by enzymes
39
13
FIGURE 4.13 The two mechanisms for terminating
neurotransmitter action in the synapse: reuptake
and enzymatic degradation.
40
Glial Function and Synaptic
Transmission

Astrocytes appear to communicate and to
modulate neuronal activity

Some communication is through gap
junctions between cells
41
FIGURE 4.14 Gap junctions.
42
14
Neurotransmitters
43
Classes of Neurotransmitters
44
Amino Acid Neurotransmitters

Usually found at fast-acting directed
synapses in the CNS

Glutamate – Most prevalent excitatory
neurotransmitter in the CNS

GABA


Synthesized from glutamate

Most prevalent inhibitory NT in the CNS
Aspartate and glycine
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15
Monoamines

Effects tend to be diffused

Catecholamines – synthesized from tyrosine


Dopamine

Norepinephrine

Epinephrine
Indolamines – synthesized from tryptophan

Serotonin
46
Steps in Synthesis of
Catecholamines
47
Acetylcholine

Acetylcholine (Ach)

Acetyl group + choline

First identified at neuromuscular junction

Neurons that release acetylcholine are
cholinergic
48
16
Unconventional
Neurotransmitters
  Soluble
gases – exist only briefly
Nitric oxide and carbon monoxide
Retrograde transmission – backwards
communication
  Endacannabinoids



anandamide is one of the two known
endocannabinoids
49
Neuropeptides

Large molecules (over 100 identified)

Example – endorphins

“Endogenous opioids”

Produce analgesia (pain suppression)

Receptors were identified before the natural
ligand was
50
Pharmacology of Synaptic
Transmission

How drugs influence synaptic activity

Agonists – increase or facilitate activity

Antagonists – decrease or inhibit activity

A drug may act to alter neurotransmitter activity at
any point in its “life cycle”
51
17
7 Steps in Neurotransmitter Action
FIGURE 4.18
52
FIGURE 4.19 Some mechanisms of
agonistic and antagonistic drug
effects.
53
Behavioral Pharmacology:
Three Influential Lines of
Research



Drugs selective to specific receptor subtypes may
exert different effects
  e.g. nicotinic vs. muscarinic acetylcholine
receptors
Discovery of the endogenous opioids provided
insight into brain mechanisms of pleasure and
pain
Effects of dopamine agonists and antagonists on
psychotic symptoms led to new treatments for
schizophrenia
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