Chapter 4: Neural Conduction and Synaptic Transmission

The Lizard: A Case of Parkinson's Disease

Like many patients with Parkinson's Disease, Roberto looked much older than he actually was
Used to be an active, thriving business man, but now is like granite and shuffles around when he
moves
The first symptom had been tremors at rest - tremors that become worst when the muscle is relaxed
Other symptoms include rigid muscles, a marked poverty of spontaneous movements, difficulty
starting to move and slowness in executing voluntary movements once they have been initiated.
Term "reptililan stare" is often used to describe the characteristic face of Parkinson's disease - lack
of blinking, widely open eyes, gazing out, motionless face
Caused by a small group of neurons called the substantia nigra unaccountably dying.
o These neurons produce dopamine, which helps control voluntary movement.
o Without dopamine, the brain begins to degrade in certain functions.
Although low dopamine levels are the cause of Parkinson's Disease, administering dopamine
directly is not a solution because dopamine does not readily cross the blood-brain barrier.
A knowledge of dopaminergetic transmitters has led to the development of an effective treatment.
o L-dopa is a precursor to dopamine which does readily cross the blood brain barrier
o L-dopa is converted to dopamine once within the brain
4.1: Resting Membrane Potential
Membrane Potential: The difference in electrical charge between the inside and the outside of the
cell.
Recording the Membrane Potential
o In order to record the membrane potential of a cell, the tip of one electrode must be positioned
in the space outside the cell and the tip of another electrode must be placed inside a cell.
o The electrode which penetrates the cell membrane must be fine enough to pierce it without
causing severe damage.
o Microelectrodes: Fine-tipped electrodes whose tips are less than one-thousandth of a
millimeter in diameter. Microelectrodes are too small to be seen by the naked eye.
Resting Membrane Potential
o The difference in potential in the extracellular fluid is 0
o The difference in potential between the extracellular fluid and the internal environment of a
neuron is -70 mV. (The resting neuron has about 70mV less electric potential energy than the
extracellular fluid outside the cell)
o Resting Potential: The steady membrane potential of a neuron at rest, usually about -70mV.
o When a neuron has a charge built up across its membrane in this manner, it is said to be
polarized.
Ionic Basis of the Resting Potential
o Ions: Positively or negatively charged particles. An ion is formed when a particle gains or loses
electrons and hence alters their electric charge. A positive ion has lost electrons, while a
negative ion has gained electrons.
o Salts in solution naturally separate into positively and negatively charged ions.
o How charge is distributed evenly across the membrane can be explained by 2 reasons:
Random Motion: Ions in neural tissue are in constant motion and particles in random motion
tend to become evenly distributed because they tend to move from areas of dense

concentration to areas of low concentration.

Electrostatic Pressure: Any accumulation of charges in one area tends to be dispersed by the
repulsion among like charges in the vicinity and the attraction of opposite charges
concentrated elsewhere.
o Despite homogenization, no single class of ions is distributed equally on the two sides of the
membrane.
o Four kinds of ions contribute significantly to the resting potential of the neuron:
Sodium Ions (Na+)
Concentration is greater outside a resting neuron than inside
Symbol developed from latin name for Sodium, Natrium
Na+ ions tend to be driven into the neurons by both the high concentration of Na+ ions
outside the neuron and the negative internal resting potential of -70 mV.
The membrane of the neuron is resistant to the passive diffusion of Na+
Sodium-potassium pumps are able to maintain a high external concentration of Na+ by
pumping them out at the same rate they flow in.
Potassium Ions (K+)
Concentration is greater inside a resting neuron than outside.
Symbol developed from latin name for Potassium, Kalium
K+ ions tend to move out of the neuron because of their high internal concentration.
o This tendency is partially offset since the inside of the neuron has a negative
potential, which attracts positively charged potassium ions.
The membrane of the neuron offers little passive resistance to the flow of K+ ions from
the inside to the outside, so they flow out of the cell body at a fairly substantial rate.
To maintain the high concentration of K+ ions, the sodium-potassium pumps in the cell
membrane pump K+ ions into the neuron at the same rate as they move out.
Chlorine Ions (Cl-)
Concentration is greater outside a resting neuron than inside
Passage of Cl- is not inhibitted by the neural membrane.
Cl- ions are actively forced out of neuron because of its negative charge of -70mV.
As Cl- ions accumulate in the area directly outside the cell, they begin to move down
their concetration gradient back into the neuron.
The neuron is in equilibrium when the electrostatic pressure for Cl- ions to move out of
the neuron is equal to the tendency for them to move down the gradient back into the
cell.
o The equilibrium point occurs at -70mV.
Various negatively charged protein ions
Most negatively charged protein ions are synthesized in the neuron and remain there.
o Two properties are responsible for the uneven distribution of ions across the membrane
One property is passive and does not require energy, the other process is active and does
require energy.
Passive Property: In resting neurons, K+ and Cl- ions pass readily through the neural
membrane, whereas Na+ ions have trouble passing through it and negatively charged
proteins do not cross the resting membrane at all.

Ion Channels: Specialized pores on the surface of the neural membrane which allow
the passage of a particular ion.
Active Property: K+ ions are continuously being drawn out of resting neurons, so the
neuron has to actively pump K+ ions back in at the same rate. Similarly, Na+ ions are
continuously being pulled into the resting neuron, so the neuron has to actively pump Na+
out of the cell at the same rate.
Energy-consuming mechanisms in the cell's membrane actively exchange Na+ ions from
within the cell with K+ ions from outside of cell.
Sodium Potassium Pumps: Specialized mechanisms on the cell membrane which
transport Na+ ions out of the cell and K+ ions into the cell.
Transporters: Mechanisms in the membrane of a cell which actively transport ions or
molecules across the membrane.

4.2: Generation and Conduction of Postsynaptic Potentials

When neurons fire they release their terminal button chemicals, called neurotransmitters.
Neurotransmitters spread out across the synaptic cleft and bind with specialized receptor molecules.
Receptor molecules are located on the receptive membranes of the next neuron in the circuit (ie. not
the sending neuron)
When a neurotransmitter binds to a receptor molecule it can generally have one of two effects:
o Depolarization: Occurs when a neurotransmitter binds to a receptor molecule, with the effect
of decreasing the resting membrane potential. For example, from -70 mV to -67 mV.
Excitatatory Postsynaptic Potentials (EPSPs): Postsynaptic depolarizations.
Depolarization makes the neuron more likely to fire.
Travel passively from their sites of generation at synapses like electricity through a
cable.
o Hyperpolarization: Occurs when a neurotransmitter binds to a receptor molecule with the
effect of increasing the resting membrane potential. For example, from -70 mV to -72 mV.
Inhibitory Postsynaptic Potentials (IPSPs): Postsynaptic hyperpolarizations.
Hyperpolarization reduces the liklihood that a neuron will fire.
Travel passively from their sites of generation at synapses like electricity through a
cable.
Graded Response: The amplitudes of both EPSPs and IPPs are proportional to the intensity of the
signals that elicit them.
o Weak signals elicit small postsynaptic potentials.
o Strong signals elicit large postsynaptic potentials.
o Opposite to all-or-none responses.
o Graded responses can vary depending on the strength of the signal, where as all-or-none
responses remain constant.
Transmission of postsnaptic potentials happens so quickly, it can be considered instantaneous for
most practical purposes.
It is important not to confuse duration with speed of transmission.
o A neuron can fire continuously for a long duration but will still have a fast transmission speed.
o The duration of firing varies widely from neuron to neuron, the transmission speed, by contrast,
does not. The transmission speed remains much more constant and nearly instantaneous.

Transmission of EPSPs and IPSPs is decremental.

o EPSPs and IPSPs decrease in amplitude as they travel through the neuron.
o Most EPSPs and IPSPs do not travel farther than couple of millimeters from their site of
generation before fading out.

4.3: Integration of Postsynaptic Potentials and Generation of Action Potentials

The postsynaptic potentials created at a single synapse generally have little effect on the firing of
the postsynaptic neuron.
The receptive area of most neurons is covered by many synapses, and whether or not the neuron
fires is determined by the net effect of all of them.
o Whether the neuron fires depends on the balance of excitatory and inhibitory signals that reach
the axon.
Axon Hillock: Conical structure at the junction between the cell body and the axon.
The potentials created at key synapses are conducted more quickly and decrementally to the axon.
Threshold of Excitation: Generally approximately -65 millivots.
o If the sum of the depolarizations and hyperpolarizations reaching the section of the axon
adjacent to the axon hillock is enough to depolarize the neuron to the threshold of excitation,
and action potential is generated.
Action Potential: Momentary reversal of the neural membrane's action potential from -70 mV to
+50 mV lasting approximately 1 ms.
o All-or-None Response: Either the response occurs to its fullest extent or it does not occur at all.
All-or-none responses are the opposite to graded responses, which occur on a continuum.
The strength of the signal does not influence the strength of the firing of the action potential.
Whether the neuron depolarizes to -64 mV or -60 mV the action potential generated is
identical.
Integration: The combining of multiple signals to create one overall signal. Neurons integrate
synaptic potentials to create (or not create) action potentials.
Spatial Summation: Three possible combinations of IPSPs and EPSPs that can occur:
o Simultaneous EPSPs form an even bigger EPSP.
o Simultaneous IPSPs form an even bigger IPSP.
o Simultaneous EPSPs and IPSPs cancel each other out.
Temporal Summation: Postsynaptic potentials produced in quick succession are more powerful in
strength than postsynaptic potentials separated by longer periods of time.
o If a particular synapse is activated and then activated again in quick succession, some of the
effect of the first stimulus will still be lingering when the second stimulus arrives. The potential
produced by the second activation will thus be superimposed on the lingering potential
produced by the first activation.
o It is possible for a brief subthreshold excitatory stimulus to fire a neuron if it is administered
twice in rapid succession.
The location of a synapse on the neuron's body has long been assumed to play a role in that
synapse's ability to effect whether or not the neuron generates an action potential.
o Some studies have shown that neurons are able to amplify the potentials generated farther away
from the cell body, calling this assumption into question.
4.4: Conduction of Action Potentials
Ionic Basis of Action Potentials

o Voltage-Activated Ion Channels: Ion channels in the neural membrane that open and close in
response to changs in potential across the cell membrane.
When an action potential is generated, voltage-activated sodium channels open wide to
allow Na+ to flow into the neuron.
This influx of Na+ drives the potential up from -70 mV to +50 mV.
The change in potential triggers voltage-activated potassium channels which then open and
drive K+ ions out of the cell. (First by the high concentration within the cell, but at the peak
of the action potential K+ ions are driven out by the positive charge)
After about 1 ms the Na+ channels close.
o Rising Phase: Phase of the action potential marked at the beginning by the reaching of the
threshold of excitation and the end by the closing of voltage-activated sodium channels.
Sodium channels open, allowing Na+ to flow into the neuron.
Potential of the neuron changes from -70 mV to +50 mV.
Change in potential triggers the openning of potassium channels.
After about 1 ms Sodium channels close.
o Repolarization Phase: Phase of the action potential marked at the beginning by the continued
outpouring of K+ ions and the ending by the closing of the last potassium channel. The neuron
remains hyperpolarized for a time after the repolarization phase of firing an action potential.
Once repolarization has been achieved, potassium channels gradually close
Because the closing of channels occurs gradually and not all at once, the neuron remains
hyperpolarized for a short period afterwards.
o The action potential involves only those ions directly in the environment surrounding the
neuron, and the number of ions that are moved is comparatively small to the overall number of
ions both inside and outisde the neuron.
o Resting membrane potential is quickly reestablished by the random movement of ions.
o Sodium-Potassium pumps have little to do with re-establishing the equillibrium membrane
potential of -70 mV.
Refractory Periods
o Absolute Refractory Period: Brief period of about 1 to 2 ms after the initiation of an action
potential during which time it is impossible to illicit a second one.
o Relative Refractory Period: Period following directly after the absolute refractory period.
During this time it possible to fire the neuron again but only with higher-than-normal levels of
stimulation
The end of the relative refractory period is marked by the level required to fire an action
potential returning to baseline.
o Refractory periods are responsible for some neural traits.
Action potentials normally only travel along axons in one direction. Portions of an axon
over which an action potential has just traveled are left momentarily refractory, so the action
potential is unable to reverse and travel back up the axon.
Neural firing intensity is related to the level of continual stimulation. If a neuron is being
continually and strongly stimulated, it will only wait until its relative refractory period to
fire. If it is being stimulated only enough to fire at baseline, it will wait until both the
absolute and relative refractory periods are over before firing another action potential.
Intermediate stimulation produces intermediate rates of firing.
Axonal Conduction of Action Potentials
o The conduction of action potentials along an axon is different from the conduction of potential
from synapses to the axon (EPSPs and IPSPs).

Conduction of action potentials is nondecremental. Action potential do not grow weaker as

they travel along the membrane.
Action potentials are conducted more slowly than postsynaptic potentials.
Conduction of action potentials is usually an active process, wheras the conduction of
potentials is generally a passive process.
o The wave of excitation triggered by the generation of an action potential near the axon hillock
always spreads passively back through the cell body and dendrites of the neuron.
o Antidromic Conduction: Axonal conduction opposite to the normal direction; Conduction
from axon terminals back towar the cell body.
Can be induced if sufficient electrical stimulation is applied to the axon terminals.
o Orthodromic Conduction: Axonal conduction in the natural direction; Conduction from the
cell body to terminal buttons.
Conduction in Myelinated Axons
o In myelinated axons, ions can pass through the axonal membrane only at the nodes of Ranvier.
o Nodes of Ranvier: Gaps between adjacent myelin segments.
o In myelinated axons, sodium channels are concentrated at the nodes of Ranvier.
o When an action potential is generated in a myelinated axon, the signal is conducted instantly
and decrementally along the first segment of myelin to the proceeding node of ranvier
o Even though the charge may have slighly weakened, it is still sufficient to open the sodium
channels and generate an entirely new action potential and the node of ranvier.
o Myelination increases the speed of axonal conduction.
o Because transmission along myelinated sections of the axon is passive, the signal is able to
jump from node to node and move at a faster rate through the axon.
o Saltatory Conduction: Transmission of action potentials in myelinated axons. Saltare means
"to skip or jump"
o Neurodegenerative diseases that attack myelin have devastating effects on neral activity and
behaviour.
The Velocity of Axonal Conduction
o The speed at which an action potential is conducted along an axon depends on two factors:
Conduction is faster in large-diameter axons.
Conduction is faster in myelinated neurons.
o Mammalian motor neurons are large and myelinated, so are able to conduct action potentials at
speeds of 100 m/s (approx. 224 miles/h)
o Small, unmyelinated axons conduct action potentials at about 1 m/s
o The maximum velocity of conduction in human motor neurons is about 60 m/s.
Conduction in Neurons without Axons
o Action potentials are the means by which axons conduct all-or-none signals non-decrementally
over relatively long distances.
o Most neurons in mammalian brains do not have axons, or have very short axons.
o Many neurons in the mammalian brain do not display action potentials.
o Conduction in interneurons is typically passive and decremental.
The Hodgkin-Huxley Model in Perspective
o The Hodgkin-Huxley model was introduced in the early 1950's and it greatly advanced our
conception of neural conduction.
o The Hodgkin-Huxley model serves as an excellent introduction to the general ways in which
neurons communicate signals, however it fails to accout for the variety, complexity and

o
o
o

plasticity of many of the neurons in the mammalian brain.

Hodgekin and Huxley studied motor neurons in squids, which are much larger and more
accessible than neurons in the central nervous system.
Hundreds of different types of neurons are found in the mammalian brain, many of which
perform functions that motor neurons do not.
Some properties of cerebral neurons are not shared in common with motor neurons.
Many cerebral neurons fire continuously even when they receive NO input. (Lisman,
Raghavachari, & Tsien, 2007; Schultz 2007; Surmeir, Mercer & Chan, 2005)
The axons of some cerebral neurons can actively conduct both graded signals and action
potentials.
Action potentials of all motor neurons are the same, but action potentials of different classes
of cerebral neurons vary greatly in duration amplitude and frequency.
Many cerebral neurons have no axons and do not display action potentials.
The dendrites of some cerebral neurons can actively conduct action potentials.
Results of studies of motor neurons should be applied to the brain with caution since cerebral
neurons are clearly far more complex than their accessible counterparts, motor neurons.

4.5: Synaptic Transmission: Chemical Transmission of Signals among Neurons

Structure of Synapses
o Neurostransmitter molecules are released from buttons into synaptic clefts, where they induce
EPSPs or IPSPs in other neurons by binding to receptors on their postsynaptic membranes.
o Axodendritic Synapse: Synapse of an axon terminal button onto the dendrite of the receiving
neuron.
Dendritic Spine: Nodules of various shapes that are located on the surfaces of many
dendrites. Many axodendritic synapses are formed on dendritic spines.
o Axosomatic Synapse: Synapse of an axon terminal button onto the soma/cell body of the
receiving neuron.
o Axodendritic and axosomatic synapses are the most common types of synapses, but there are
other varieties.
Dendrodendritic Synapse: Synapse of a dendrite terminal button onto the dendrite of the
receiving neuron. Interesting neurons because they are often able to communicate
bidirectionally between two cells.
Axoaxonic Synapse: Synapse of an axon terminal button onto the axon terminal button of
the receiving neuron; Particularly important synapses because they mediate presynaptic
facilitation and inhibition. Axoaxonic synapses can selectively favour or inhibit the effects
of that button on the postsynaptic neuron.
The advantage to this system is that axoaxonic synapses can affect a single terminal
button/synapse system and not the entire presynaptic neuron like and IPSP or EPSP
would.
o Directed Synapse: Synapse at which the site of the neurotransmitter release and the site of
neurotransmitter reception are in close proximity.
Common arrangement for synapses.
o Nondirected Synapse: Synapses at which the site of release is at some distance from the site of
reception.
Variscosity: Bulge or swelling that occurs along the axon; Releases neurotransmitters in a
disperse pattern in the surrounding environment; Example of non-directed synapses; Often
called string of bead synapses;

Synthesis, Packaging and Transport of Neurotransmitter Molecules

o Two basic categories of neurotransmitter molecules: Small and large.
Small neurotransmitters are of several types.
Typically synthesized in the cytoplasm of the terminal button and packaged in synaptic
vesicles by the button's golgi complex.
Synaptic Vesicle: Small, spherical membranes that store neurotransmitter molecules and
release them into the synaptic cleft.
Golgi Complex: Structures in the cell bodies and terminal buttons of neurons that
package neurotransmitters and other molecules into vesicles.
Once filled with small neurotransmitters, the vesicles are stored in clusters next to the
presynaptic membrane.
Large neurotransmitters are all neuropeptides.
Neuropeptide: Short amino acid chains comprising of between 3 and 36 amino acids;
Essentially act like short proteins;
o Synthesized with other proteins - in the cytoplasm of the cell body on ribosomes.
o Packaged in vesicles by the cell body's golgi complex.
o Vesicles are transported by microtubules to the terminal buttons.
o Vesicles moving in this way move at a speed of about 40 cm/day.
Vesicles that contain neuropeptides are generally larger than small molecule vesicles.
Although many neurons synthesize and release only a single neurotransmitter, some neurons
may synthesize two.
Coexistance: The presence of more than one neurotransmitter in the same neuron.
Most documented cases of coexistance have involved a single neuropeptide and a single
small-molecule neurotransmitter.
Release of Neurotransmitter Molecules
o Exocytosis: The process of neurotransmitter release.
o When a neuron is at rest, synaptic vesicles containing neurotransmitters have a tendency to
congregate near sections of the presynaptic membrane that are rich in voltage-activated calcium
channels.
o When stimulated by an action potential, the cacium channels open, allowing Ca2+ ions to enter
the button.

o The entry of Ca2+ ions causes the synaptic vesicles to fuse with the membrane of the button and
consequently release their contents into the synaptic cleft.

o For many synapses an action potential causes the release of a single synaptic vesicle.
(Neuropeptides only)
o Small-molecule neurotransmitters are typically released in a pulse each time an action potential
triggers a momentary influx of Ca2+ ions.
Activation of Receptors by Neurotransmitter Molecules
o Neurotransmitter molecules produce signals in postsynaptic neurons by binding to receptors.
o Receptor: Protein that contains binding sites for only particular neurotransmitters
Neurotransmitters can only influence cells that have receptors for it.
Ligand: A molecule that binds to another molecule; neurotransmitters are ligands of their
receptors;
Most neurotransmitters bind to several different types of receptors.
Receptor Subtypes: Different types of receptors to which a particular neurotransmitter can
bind.

Different subtypes for the same neurotransmitter are usually located in different areas of
the brain.
Different subtypes typically respond to the same neurotransmitter in different ways.
An advantage to having multiple receptor subtypes is that the same neurotransmitter is
able to be used to transmit multiple different messages to different parts of the brain.
o Binding of a neurotransmitter to one of its receptor subtypes can influence a post-synaptic
neuron in one of two fundamentally different ways:
Ionotropic Receptors: Receptors associated with ligand-activated ion channels.
When a neurotransmitter molecule binds to an ionotropic receptor, the associated ion
channel usually opens or closes immediately, inducing immediate post-synaptic
potential.
EPSPs occur when the neurotransmitter opens sodium channels, therby increasing the
flow of Na+ ions into the neuron.
IPSPs occur when the neurotransmitter opens potasium or chlorine channels, increasing
the flow of K+ ions out of the neuron, or the flow of Cl- into the neuron.
Less prevalent than metabotropic receptors.
Metabotropic Receptors: Receptors that are associated with signal proteins and G
Proteins.
Effects of metabotropic receptors are slower to develop, longer lasting, more diffuse and
more varied.
More prevalent than ionotropic receptors.
Many different kinds of metabotropic receptors, but each is attached to a serpentine
signal protein that winds its way back and forth through the cell membrane 7 times.
The metabotropic receptor is attached to a portion of the signal protein outside the
neuron.
The G protein is attached to a portion of the signal protein inside the neuron.
When a neurotransmitter binds to a metabotropic receptor, a subunit of the associated G
protein breaks away.
One of two things happens depending on the particular G protein:
o The subunit may move along the inside surface of the membrane and bind to a
nearby ion channel, inducing either an EPSP or IPSP
o May trigger the synthesis of a chemical called a second messenger.
o Second Messenger: A chemical synthesized in a neuron in response to the binding
of a neurotransmitter to a metabotropic receptor in the cell membrane.
Once created , a second messenger diffuses through the cytoplasm and may
influence the activities of the neuron in a variety of ways.
For example, it could enter the nucleus and bind to the DNA, thereby
influencing genetic expression.
o The binding of a neurotransmitter to a metabotropic receptor can have long-lasting
effects.
Autoreceptors: metabotropic receptors that bind to their own neuron's neurotransmitter
molecules and are located on the presynaptic, rather than the postsynaptic membrane.
o Typical function of autoreceptors is to monitor the amount of neurotransmitter
molecules in the synapse, to reduce subsequent release when the levels are high and
to increase subsequent release when te are low
G Proteins: Guanosine-triphosphate-sensitive proteins;

o Differences in small-molecule and neuropeptide neurotransmitter patterns of release and

receptor binding suggest that they serve different functions.
o Small molecule neurotransmitters tend to be released into directed synapses and to activate
either ionotropic receptors or metabotropic receptors that act directly on ion channels.
o Neuropeptides tend to be released diffusely, and virtually all of them bind to metabotropic
receptors that act through second messengers.
o The function of small-molecule neurotransmitters appears to be the tranmission of rapid, brief
excitatory or inhibitory signals to adjacent cells.
o Function of neuropeptides appears to be the transmission of slow, diffuse signals.
Reuptake, Enzymatic Degradation and Recycling
o Two mechanisms terminate synaptic messages.
Reuptake: The more common of the termination mechanisms. Most neurotransmitters are
drawn back into the pre-synaptic button shortly after being released. Transporter
mechanisms allow for neurotransmitter molecules to be brought back to the presynaptic
button.
Enzyme Degradation: The breakdown of chemicals by enzymes - one of the two
mechanisms for deactivating released neurotransmitters.
Acetylcholine is one of the few neurotransmitters where enzyme degradation is the main
method for deactivation.
Acetylcholine must be broken down by the enzyme acetylcholinesterase.
o Once released, neurotransmitter molecules or their broken down products are drawn back into
the button and receycled, regardless of the method used to deactivate them.
o Even vesicles are reused to create new vesicles once their immediate function has been served.
Glial Function and Synaptic Transmission
o Astrocytes have been shown to release chemical transmitters, to conduct signals, and to
participate in neurotransmitter reuptake.
o The importance of glial cells in brain function is suggested by the greater prevalence of these
cells in intelligent organisms.
o Gap Junctions: Narrow spaces between adjacent neurons that are bridged by fine tubular
channels called connexins that contain cytoplasm.
The cytoplasm of the two neurons is consequently continuous, allowing for signals and
small molecules to pass through from one neuron to the next.
Gap junctions are sometimes called electrical synapses.
Common in invertebrate systems, but difficult to establish in mammals.
Seem to be an integral feature of local neural inhibitory circuits.
Astrocytes have been shown to commnicate with each other, neurons and other cells
through gap junctions.
The role of gap junctions in nervous system activity is both underappreciated and poorly
understood.
Gap junctions are less selective than synapses, but they have two advantages
Communication is very fast because it does not involve active mechanisms
Gap junctions permit communication in either direction.

4.6: Neurotransmitters
Well over 100 different neurotransmitters active in the body
3 classes of conventional small-molecule neurotransmitters:

o Amino acids
o Monoamines
o Acetylcholine
The fourth class of small-molecule neurotransmitters is often referred to as unconventional
neurotransmitters because their mechanisms of action are unusual
There is only one class of large-molecule neurotransmitter:
o Neuropeptides
Most neurotransmitters produce either excitation or inhibition, but not both
o A few select neurotransmitters cause excitation upon binding to certain types of neurons (ie. in
differing areas of the brain), but inhibition when binding to others.
Amino Acid Neurotransmitters: A class of small-molecule neurotransmitters, which includes the
amino acids glutamate and GABA
o Four most widely studied amino acid neurotransmitters are:
Glutamate: The brain's most prevalent excitatory neurotransmitter, whose excessive release
causs much of the brain damage resulting from cerebral ishemia.
Aspartate: An amino acid neurotransmitter that is a constituent of many of the proteins that
we eat.
Glycine: An amino acid neurotransmitter that is a constituent of many of the proteins that
we eat.
Gamma-Aminobutryic Acid (GABA): The amino acid neurotransmitter that is synthesized
from glutamate; The most prevalent inhibitory neurotransmitter in the mammalian nervous
system, however it does have excitatory effects at some synapses.
Monoamine Neurotransmitters: Class of small-molecule neurotransmitters synthesized from a
single amino acid;
o Slightly larger than amino acid transmitters
o Effects tend to be more diffuese than amino acid transmitters
o Monoamines tend to cluster in small groups and are found, for the most part, in the brain stem.
o Neurons that use monoamines tend to have highly branched axon structures with many
variscosities (string of bead synapses) from which monoamine neurotransmitters are diffusely
released into the extracellular fluid.
o Four monoamine neurotransmitters:
Dopamine: One of the three catecholamine neurotransmitters; dopaminergetic neurons are
damaged by parkinson's disease.
Tyrosine is converted to L-dopa, which is in turn converted to dopamine.
Epinephrine: One of the three catecholamine neurotransmitters.
Neurons that release epinephrine have the enzyme required to convert dopamine to
norepinephrine as well as an additional enzyme which converts norepinephrine to
epinephrine.
Neurons that release epinephrine are called adrenergic.
Ephinephrine used to be called adrenaline until the name adrenaline was patented as a
brand name.
Norepinephrine: One of the three catelcholamine neurotransmitters.
Neurons that release norepinephrine have an extra enzyme that converts dopamine to
norepinephrine.
Neurons that release norepinephrine are called noradrenergic.
Norepinephrine used to be called noradrenaline until adrenaline was patented as a brand

name.
Serotonin: An inolamine neurotransmitter; the only member of this class of monoamine
found in the mamallian nervous system.

o Two classes of monoamine neurotransmitters:

Catecholamines: The three monoamine neurotransmitters that are synthesized from the
amino acid tyrosine: dopamine, epinephrine, and norepinephrine
Indolamines: The class of monoamine neurotransmitters that are synthesized from
tryptophan; seratonin is the only member of this class found in the mammalian nervous
system.
Acetylcholine: A neurotransmitter that is created by the addition of acetyl group to a choline
molecule.
o The neurotransmitter at neuromuscular junctions, at many of the synapses in the automic
nervous system and at synapses in several parts of the central nervous system.
o Acytlycholine is broken down in the synapse by the enzyme acetylcholinase
o Neurons that release acetylcholine are said to be cholinergic.
Unconventional Neurotransmitters
o Soluble-Gas Neurotransmitters: A class of unconventional neurotransmitters that includes
nitric oxide and carbon monoxide; shown to be involved in retrogade transmission; At some
synapses feeback signals are transmitted in the opposite direction from normal - from the
postsynaptic neuron back to the presynaptic neuron; Function seems to be to regulate the
presynaptic neuron.
Nitric Oxide: A soluble-gas neurotransmitter
Carbon Monoxide: A soluble-gas neurotransmitter
o These neurotransmitters are produced in the neural cytoplasm and immediately diffuse through
the cell membrane into the extracellular fluid and then into nearby cells.
o These neurotransmitters easily pass through cell membranes because they are soluble in lipids.
o Stimulate the production of a second messenger before being converted into other molecules.
o Difficult to study because they exist for only a few seconds.
o Endocannabinoids: Neurotransmitters that are similar to delta-9-tetrahydrocannibinol (THC)
Anandamide: From the sanskrit word meaning 'Eternal Bliss';
Like soluble-gases, endocannabinoids are produced immediately before they are released
and broken down immediately after having their effect.
Synthesized from fatty compounds in the cell membrane.
Tend to be released from dendrites and the cell body.
Tend to have most of their effects on presynaptic neurons, inhibitting subsequent synaptic
transmission
Neuropeptides
o Over 100 neuropeptides have been identified
o The action of each neuropeptide depend on its amino acid sequence.
o Common to group neuropeptide neurotransmitters into 5 loose categories while recognizing that
neuropeptides often have alternative functions in multiple categories:
Pituitary Peptides: Contains neuropeptides that were first identified as hormones released
by the pituitary.
Hypothalamic Peptides: Contains neuropeptides that were first identified as hormones
released by the hypothalamus.

Brain-gut Peptides: Contains neuropeptides that were first discovered in the gut.
Opioid Peptides: Contains neuropeptides that are similar in structure to the active
ingredient of opium.
Miscellanious Peptides: All neuropeptides that do not fit into the other four groupings of
neuropeptides.

4.7: Pharmacology of Synaptic Transmission and Behaviour

Most of the methods psychologists use to study the effects of different neurotransmitters are
pharmacological (ie. involving drugs)
Drugs have two fundamental types of effect on the synaptic transmission, either they facilitate it or
they inhibit it.
Agonists: Drugs that facilitate the effects of of a particular neurotransmitter.
o Drug may increase the synthesis of neurotransmitter molecules.
o Drug may increase the number of neurotransmitter molecules by destroying degrading enzymes.
o Drug may increase the release of neurotransmitter molecules from terminal buttons.
o Drug may bind to autoreceptors and bolck their inhibitory effect on neurotransmitter release.
o Drug may bind to the postsynaptic receptor and either activate them or increase the effect on
them of neurotransmitter.
o Drug may block the deactivation of neurotransmitter by blocking degradation or blocking
reuptake.
Antagonists: Drugs that inhibit the effects of a particular neurotransmitter.
o Drug blocks the synthesis of neurotransmitter molecules (eg. by destroying synthesizing
enzymes)
o Drug may cause the neurotransmitter molecules to leak from their vesicles and be destroyed by
degrading enzymes.
o Drug may block the release of neurotransmitter molecules from terminal buttons
o Drug may activate autoreceptors and inhibit neurotransmitter release.
o Drug may be a receptor blocker. It may bind to the postsynaptic receptors and block the effect
of neurotransmitters.
How Drugs Influence Synaptic Transmission
o Seven general steps are common to most neurotransmitters:
Synthesis of the neurotransmitter
Storage in vesicles
Breakdown in the cytoplasm of any neurotransmitter that leaks from the vesicles
Exocytosis
Inhibitory feedback via autoreceptors
Activation of postsynaptic receptors
Deactivation
Behavioural Pharmacology: Three Influencial Lines of Research
o Wrinkles and Darts: Discover of Receptor Subtypes
Some acytlcholine receptors bind to nicotine, whereas other acetylcholine receptors bind to
muscarine.
These two types of acetylcholine receptors thus became known as nicotinic receptors and
muscarinic receptors.
Nicotinic and muscarinic receptors are distributed differently in the nervous system, have
different modes of action and produce different behavioural effects.

Many nicotinic receptors occur at the junctions between motor neurons and muscle fibres
Many musarinic receptors are located in the autonomic nervous system.
Nicontinic receptors are ionotropic, while muscarinic receptors are metabotropic.
Atropine: The main active ingredient in belladona; Receptor blocker that binds to
muscarinic receptors and prevents acetylcholine from binding to them.
The disruptive effects of high doses of atropine on memory was one of the earliest clues
that cholinergic mechanisms play are role in memory.
Curare: Extract of certain class of woody vines used as tips for poison darts; Receptor
blocker at cholinergic synapses but it acts on nicotinic receptors, blocking transmission at
neuromuscular junctions, paralyzing its recipients and killing them by blocking their
respiraton.
o Botox: Neurotoxin released by a bacterium often found in spoiled food; Nicotinic antagonist;
Blocks release of acetylcholine at neuromuscular junctions, making it a deadly poison.
o Pleasure and Pain: Discovery of Endogenous Opioids
In the 1970's opiate drugs such as morphine were found to bind effectively to receptors in
the brain.
These receptors were generally found in the hypothalamus and other limbic areas.
Most concentrated region of opioid receptors is located in the brain stem, near the cerebral
aqueduct connecting the third and fourth ventricles.
Microinjection of morphine into the periaquiductal grey or electrical stimulation of the same
area, produces analgesia.
Endogenous: Occurring naturally within the body
Several families of endogenous opioids have been identified.
Enkephalins: Meaning "in the head"; First endogenous opioid discovered;
All endogenous opioid neurotransmitters are neuropeptides, and their receptors are
metabotropic.
o Tremors and Insanity: Discovery of Antischizophrenic Drugs
Two drugs were found by coincidence that are not structurally related, but produce similar
patterns in behavioural changes
Neither drug appeared to be effective until the patient had been taking it for 3 weeks.
After the three weeks, patients would begin to develop parkinson's type symptoms, such
as trembling at rest.
Researchers used this evidence to make two discoveries:
Parkinson's disease is associated with the degeneration of the main dopamine pathway
Dopamine agonists (such as cocaine and amphetamines) produce temporary parkinson's
type symptoms.
These findings suggested that schitzophrenia was partly caused by excessive dopamine
activity at dopamine synapses
Antagonists to dopamine were hypothesized to be an effective solution for schitzophrenic
patients.
The one particular dopamine receptor, D2 receptor plays a key role in scitzophrenia, and it
was found that drugs that block those receptors are the most effective at relieving
schitzophrenic symptoms.