The Neuronal Membrane At Rest
Alec Jotte
The Neuronal Membrane At Rest
Introduction

Action Potential – the nerve impulse. The special type of signal that is carried by neurons.

Excitable Membrane – membranes of cells capable of generating and conducting action potentials
(neurons and muscle cells)

Resting Membrane Potential – in a resting neuron, the cytosol along the inside surface of the
membrane has a negative electrical charge when compared to the outside. Action potential is simply a
brief reversal of this condition.
The Cast of Chemicals

Ion – electrically charged atoms who are responsible for the resting and action potentials. They are
dissolved in the water that is the primary ingredient of the fluid inside (cytosol) and surrounding
(extracellular fluid) the neuron.

Cation – a positively charged ion. For cellular neurophysiology; Na +, K+, Ca2+

Anion – a negatively charged ion; Cl-

Phospholipid bilayer – hydrophilic heads interact with the water outside/inside the cell, hydrophobic
tails create a layer between the phosphate heads. Effectively isolates the cytosol of the neuron from the
extracellular fluid

Peptide Bond – bonds that connect amino acids  this forms the primary structure of the protein.
o Proteins are important in distinguishing the neuronal cell: enzymes catalyze chemical reaction,
cytoskeleton gives the special shape, and receptors are sensitive to neurotransmitters  all
these are proteins.
o
Primary structure – order of amino acids. Secondary structure – shape of chain (alpha helix).
Tertiary structure – 3 dimensional shape changes (bends, folds). Quaternary structure – when
differen polypeptide chains bond together to form a larger molecule.

Polypeptide – proteins made of a single chain of amino acids

Ion Channel – channels made of proteins, usually 4-6 that exist throughout the membrane.

Ion Selectivity – certain channels only allow certain ions through. Potassium channels are selectively
permeable to K+, calcium channels to Ca2+, etc.

Gating – the ability of channels to open or close based on changes in their environment.

Ion Pump – proteins in the membrane that use energy from ATP breakdown to transport certain ions
across the membrane and concentration gradient.
The Movement of Ions

Diffusion – net movement of ions from region of high concentration to regions of low concentration

Concentration Gradient – a difference in concentration. Ions will flow down a concentration gradient
when diffusing

Electrical Current (I) – the movement of electrical charge, represented by the symbol I and measure in
units called amperes (amps)

Electrical Potential (Voltage, V) – the force exerted on a charged particle. It reflects the difference in
charge between the anode and cathode. Measured in volts. (anode) -6
6(cathode)  the voltage is 12

Electrical Conductance – the relative ability of an electrical charge to migrate from one point to
another. Measured in siemens (S) and represented by symbol g. Dependent on the number of particles
available to carry electrical charge and the ease with which those particles can travel through space.

Electrical Resistance – the relative inability of an electrical charge to migrate. Represented by R and
measured in Ohms. R = 1/g

Ohm’s Law – relationships between potential (V), conductance(g), and the amount of current (I).
o I = gV

There will be no current if electrical potential, or conductance is 0. Likewise, even if
the conductance and potential are great, if there is no current, nothing will happen.

Driving an ion across the membrane electrically, therefore, requires that (1) the
membrane has channels permeable to that ion and (2) there is an electrical potential
difference across the membrane.
The Ionic Basis of the Resting Membrane Potential

Membrane Potential – the voltage across the neuronal membrane at any moment, represented by the
symbol Vm
o
The resting potential of a typical neuron is -65mV
o
Very sensitive to changes in [K+]0 because the membrane is primarily permeable to K+

Microelectrode – a thing glass tube with an extremely fine tip that penetrates the membrane of a
neuron with minimal damage; used to measure V m

Ionic Equilibrium Potential (Equilibrium Potential, EION) – the electrical potential difference that
exactly balances an ionic concentration gradient, ie, not net flow of ions occurs because electrical pull
= push due to concentration gradient
o
How? K+ has a way stronger concentration on the inside compared to the outside. Although
the inside is electrically neutral, and so is the outside (because the ratio of + to – is equal), the
concentrations of the ions differ greatly. Now, if a K + channel were to open, the K+ would
rush out of the cell, down the concentration gradient. Eventually, a positive charge starts to
build on the outside of the cell membrane, discouraging K+ from leaving the cells through the
channels (because it is positively charged on the other side). Eventually the rate of pulling K+
in due the electrical imbalance = rate of diffusion of K + to the outside of the membrane, and
the resting potential is established.
o
Key Four Points

*Large changes in membrane potential are caused by miniscule changes in ionic
concentrations.

*The net difference in electrical charge occurs at the inside and outside surfaces of
the membrane. The large majority of the cytosol remains electrically neutral, just the
part right outside the membrane is upset by the electrical imbalance.

*Ions are driven across the membrane at a rate proportional to the difference between
the membrane potential (at a given point in time) and the equilibrium potential (the
set voltage that equals the ionic concentration gradient, allowing no ions to flow)

*If the concentration difference across the membrane is known for an ion, an
equilibrium potential can be calculated for that ion. Ie, if the equilibrium potential
will be positive or negative (if the inside of the cell is slightly negative, then the
equilibrium potential will be negative).

Ionic Driving Force – The difference between the real membrane potential and the equilibrium
potential (Vm – EION) for a particular ion

Nernst Equation – method of calculating the exact value of an equilibrium potential.
o EION = (2.303) ((RT)/(zF)) (log ([ion] 0/[ion]i))


EION = ionic equilibrium potential

R = gas constant

T = absolute temperature

Z = charge of the ion

F = Faraday’s constant

Log = base 10 logarithm

[ion]0 = ionic concentration outside the cell

[ion]i = ionic concentration inside the cell
Sodium-Potassium Pump – enzyme that breaks down ATP in the presence of internal Na +. The energy
released by this exchanges internal Na+ for external K+. This ensures that K+ is concentrated on the
inside of the neuron, and Na+, on the outside. Estimated that this uses 70% of all ATP used by the brain.
Ion
K
Concentration
Concentration
Ratio
EION
Outside (in mM)
Inside (in mM)
Out : In
(at 37 C)
5
100
1 : 20
-80 mV
150
15
10 : 1
62 mV
2+
2
0.0002
10,000 : 1
123 mV
-
150
13
11.5 : 1
-65 mV
+
Na+
Ca
Cl

Calcium Pump – an enzyme that actively transports Ca2+ out of the cytosol across the membrane.

Goldman Equation – a mathematical formula that takes into consideration the relative permeability of
the membrane to different ions, and can be used to calculate the resting membrane potential.

Depolarization – a change in membrane potential from the normal resting value (-65mV) to a less
negative value is called a depolarization of the membrane. Increasing extracellular potassium
depolarizes neurons. Ie, if [K+] outside the neuron were to be 20, the resting potential would drop to
-17mV

Blood-Brain Barrier – a specialization of the walls of brain capillaries that limits the movement of
potassium (and other blood borne substances, such as lead) into the extracellular fluid of the brain
o
Glia, especially astrocytes, also help control extracellular K + levels when concentrations rise.
Glia will pull K+ into the membrane via potassium pumps causing the glia to depolarize
instead of the neurons
o
However, muscle cells don’t have a blood barrier and so increases in [K +] in the blood can
still have major consequences.

*The electrical potential difference across the membrane can be thought of as a battery whose charge is
maintained by the work of the ion pumps.
Chapter 4: The Action Potential
Alec Jotte
Properties of the Action Potential

Rising Phase – first part of the action potential. Rapid depolarization of the membrane

Overshoot – the part of the action potential where the inside of the neuron is positively charged with
respect to the outside

Falling Phase –the part of the action potential including rapid repolarization until the membrane is
actually more negative than the resting potential

Undershoot (After-Hyperpolarization) – the part of the action potential where the membrane is more
negative than the resting potential

Threshold – the critical level of depolarization that must be crossed in order to trigger an action
potential. Action potentials are caused by depolarization of the membrane beyond the threshold.
o
What triggers this? Depends on the type of neuron. Those right against the skin open Na+
channels when the membranes are stretched (such as thumbtack man). In interneurons, certain
neurotransmitters trigger the opening of those Na+ channels. Action potentials are like a
camera – you push down until you cross the threshold, then *click.*

Absolute Refractory Period – once one action potential is initiated, it is impossible to initiate another
for about 1 milisecond. This period of time is the absolute refractory period.

Relative Refractory Period – it can be relatively difficult to initiate another action potential for several
milliseconds after the end of the absolute refractory period. This is the relative refractory period, and
during this time, the amount of current required to depolarize the neuron to action potential is higher
than normal.
The Action Potential, in Reality

Key Terms
o Voltage Clamp – key device in determining the transient rises in number of open sodium or
potassium channels
o
Voltage-gated Sodium Channel – a protein that forms a pore in the membrane and is highly
selective to Na+ ions. The pore is opened and closed by changes in the electrical potential of
the membrane.

When the membrane is depolarized to threshold, the molecule (it’s a protein that’s
actually just one really long polypeptide) twists into a shape that allows Na+ to enter
the cell through the pore. The pore has a “filter” that is sized perfectly for Na+. K+ is
too large to fit through. Ions must be attached to a “chaperone” water molecule

These channels (1) open with little delay, (2) stay open for about 1 msec and then
close (inactive), and (3) cannot be opened again by depolarization until the
membrane potential returns to a negative value near threshold
o
Channelopathy – a human genetic disease casued by alterations in the structure and function
of ion channels
o
Tetrodotoxin (TXX) – toxin in a puffer fish that selectively blocks the Na+ channels
o
Voltage-gated Potassium Channel – potassium channels that open about 1msec after
depolarization.

Content
o
Depolarization of the cell during the action potential is caused by the influx of sodium ions
across the membrane, and repolarization is caused by the efflux of potassium ions.
o
So once threshold is met, Na+ channels fly open, and sodium desperately wants to get inside
because Vm = -65mV, and sodium’s Equilibrium Potential is +62mV. So the drive on the Na+
ions to get into the cell is very high. So Na+ enters the cell, this is the rising phase. Then, once
you hit a certain point, the sodium channels close. Potassium channels are still open however,
and so K+ flows out of the cell, trying to make its way back to its equilibrium potential,
-80mV. In the meantime, sodium-potassium pumps are pumping Na+ out of the cell, and K+
back in.

The rising phase is explained by inward sodium current, and the falling phase is
explained by an outward potassium current.

The action potential therefore is caused by the movement of ions through channels
that are gated based on changes in the membrane potential.

The rising phase was indeed caused by a transient increase in gNa (the electrical
conductance proportional to the number of sodium channels open), and the falling
phase was caused by a transient increase in gK

Ok, so what?
o Threshold – membrane potential at which enough voltage-gated sodium channels open, so
that the membrane is more permeable to sodium than to potassium.
o
Rising Phase – Na+ ions rush into the cell through the open sodium channels, because the
inside of the membrane has a negative electrical potential (ie, there is a large driving force on
the Na+ ions)
o
Overshoot – the relative permeability of the membrane greatly favors sodium, and so the
membrane potential goes to a value close to the equilibrium potential of sodium (E Na) which
is greater than 0 mV.
o
Falling Phase – first, the voltage-gated sodium channels shut. Second, the voltage-gated
potassium channels finally open. There’s a great driving force on K+ ions when the membrane
is strongly depolarized, and so K+ rushes out of the cell through the open channels, causing
the membrane potential to be negative again.
o
Undershoot – because the potassium channels from the falling phase are still open, the
membrane is more permeable to potassium than usual. This causes a hyper-polarization in
which the membrane voltage is more negative than the resting potential, until the potassium
channels close again.
o
Absolute Refractory Period – sodium channels inactivate when the membrane is depolarized.
They cant be activated again, and therefore another action potential cant occur, until the
membrane potential goes sufficiently negative to deactivate the channels.
o
Relative Refractory Period – the membrane potential stays hyperpolarized until the voltagegated potassium channels close, and so until that happens, more current is required to bring
the membrane potential to threshold.
o
**Meanwhile, sodium potassium pumps are working to reinstate the gradients by pushing
Na+ out of the cell and K+ back into the cell

Action Potential Conductioin
o
The movement of the signal is a lot like the lighting of a fuse. Once section of the membrane
is depolarized and then will depolarize the segment right next to it over and over until it
reaches the axon terminal. The signal can travel in either direction, but cant turn back on itself
o
Action potential conduction velocity increases with increasing axonal diameter. Imagine a
hose: water will flow through it. But if it’s narrow with holes in the side, the water will
choose to go out of the hose. Same deal with action potential.
o
Fortunately, vertebrates have another way to increase action potential velocity: myelin sheaths.
The sheaths are composed of many layers of membrane provided by glial support cells
(Schwann in the peripheral nervous system and oligodendroglia in the CNS). Myelin is like
wrapping tape around the leaky hose – it forces the Na+ current to move down the axon
instead of out. Breaks in the insulation (Nodes of Ranvier) occur so that ions can cross the
membrane to generate action potentials.
o
Saltatory Conduction: propagation of the action potential along myelinated axons; it basically
“skips” from node to node because the myelin prevents the current from leaving, and so it can
only leave or enter through those nodes.
Action Potentials, Axons, and Dendrites

The membranes of dendrites and neuronal cell bodies don’t generate sodium-dependent action
potentials because they have very few voltage-gated sodium channels.

Spike-Initiation Zone – the zone of the axon where the specialized gated ion channels exist – basically
the part of the neuron capable of initiating its own action potential. Usually the axon hillock, but in
sensory neurons it occurs near the sensory nerve endings
Synaptic Transmission
9/2/2015 1:25:00 AM
Introduction

Synaptic transmission – the process of information transfer at a synapse

Electrical synapse – electrical current flowing from one neuron to the next. This type of synapse is
common in the mammalian brain

Chemical synapse – chemical neurotransmitters transfer information from one neuron to another at the
synapse. Comprise the majority of synapses in the brain.
Types of Synapses

Electrical
o Gap junction – specialized sites at which electrical synapses occur. At a gap junction,
membranes of two cells are very close together – the tiny gap between them is spanned by
proteins called connexins. These proteins form a channel between the two cells and ions are
free to flow from one cell to the next. As a result, most are bidirectional (can go either way)
unlike chemical synapses. Cells connected by these are said to be electrically coupled.
Important for places where normal function requires high synchronization.
o
Postsynaptic potential – when an action potential is trigger in one cell, some of the ionic
current will flow through the gap junction into the next neuron. This current causes a
postsynaptic potential (PSP) in that second neuron, but it usually is very small and often not
enough in and of itself to trigger an action potential in the second neuron. However, one
neuron will usually form many electrical synapses with other neurons, so many PSPs
occurring at once could be strong enough to trigger AP

Chemical – pre and post synaptic membranes are separated by a small synaptic cleft (10 wider than the
separation of a gap junction). Presynaptic side of the cleft is referred to as the presynaptic element and
is usually an axon terminal. Terminal is full of synaptic vesicles.
o
Secretory granule (dense-core vesicle) – large vesicles in the axon terminal containing
soluable protein.
o
Membrane differentiations – dense gatherings of protein on just next to (on the inside) and
within the pre and post synaptic membranes are referred to as membrane differentiations
o
Active zone – the actual sites of neurotransmitter release; proteins will jut into the cytoplasm
of the terminal along the intracellular face of the membrane – the tiny field of pyramids
o
Postsynaptic density – the protein thickly accumulated in and just under the postsynaptic
membrane. These proteins convert the intercellular signal (neurotransmitters) into an
intracellular signal (change in membrane potential or other chemical change)
o
Neuromuscular junction – chemical synapses of motor neurons and skeletal muscle. Fast and
reliable. AP in the motor neuron always causes AP in the muscle cell it innervates.
Presynaptic terminal has many active zones and the synapse is just really big.
o
Motor end-plate – the post-synaptic membrane of a neuromuscular junction – this is the
membrane of the muscle cell. They have many shallow folds to increase surface area and
therefore also the number of receptors. Allows many neurotransmitters to be realized focally
onto a large surface of chemically sensitive membrane

CNS Synapses
o Postsynaptic membrane is on a dendrite: axodendritic
o
Postsynaptic membrane is on another axon: axoaxonic
o
Postsynaptic membrane is on the cell body: axosomatic
o
Dendrites form synapses with each other: dendrodendritic
Principles of Chemical Synaptic Transmission

Most neurotransmitters fall into one of three categories:
o 1. Amino acids – small organic molecule (synaptic vesicles)
o
o

For example:

Glutamate (Glu)

Gamma-amniobutyric acid (GABA)

Glycine (Gly)
2. Amines – small organic molecule (synaptic vesicles)

Acetylcholine (ACh)

Dopamine (DA)

Epinephrine

Histamine

Norepinephrine

Serotonin (5-HT)
3. Peptides – large molecules (secretory granules)

CCK

Dynorphin

Glutamate (Glu), Gamma-amniobutyric acid (GABA), and Glycine (Gly) – fast chemical synaptic
transmission at most CNS synapses is mediated by these amino acids.

Acetylcholine (ACh) – mediates fast synaptic transmission at all neuromuscular junctions

Neurotransmitter Synthesis and Storage
o Some amino acids are very prevalent in all cells (Glu, Gly). Others, (GABA) are make only
by the neurons that release them. Specific synthesizing enzymes are transported to the axon
terminal where they locally and rapidly direct transmitter synthesis.

Transporter – special proteins present in the vesicle membranes who are responsible
for collecting and concentrating neurotransmitters that have been synthesized in the
cytosol
o
Peptides – a long peptide is synthesized in the rough ER, and the golgi will split it. One of the
smaller peptide fragments is the neurotransmitter. Secretory granules full of it will bud off
from the golgi and are transported to the axon terminal via axoplasmic transport.

Neurotransmitter Release – triggered by the arrival of an action potential in the axon terminal
o Voltage-gated calcium channel – depolarization of the terminal membrane causes these,
located in the active zones, to open. Ca2+ will flood into the cell – this is the signal that causes
the neurotransmitter to be released from the synaptic vesicles

Exocytosis – the membrane of the synaptic vesicle will fuse to the presynaptic
membrane at the active zone, allowing the contents of that vesicle to spill out into the
synaptic cleft. Certain vesicles are already “docked” at the active zones (via
interaction of their proteins), and increased Ca2+ causes proteins to alter their
formation so that the membranes form a pore that allows neurotransmitter to escape
into the cleft.

Peptide neurotransmitters & secretory granules aren’t located at the active
sites, and so don’t get set off by every influx of Ca2+. This is why they take
longer – they require more Ca2+ to travel a longer distance.

Endocytosis – method by which the vesicle membrane is recovered. The recycled
vesicle is refilled with neurotransmitter and used again

Neurotransmitter Receptors and Effectors
o Transmitter-gated ion channel – membrane-spanning proteins that are made of 4-5 subunits
that form a pore between them. Neurotransmitters cause a conformational change that allows
them to open. Do not show the same degree of ion selectivity as do voltage gated channels.

Excitatory postsynaptic potential (EPSP) – the postsynaptic membrane
depolarization caused by the presynaptic release of a neurotransmitter. This occurs
when a transmitter-gated ion channel opens and Na+ flows into the cell through it
(ACh-gated and glutamate-gated ion channels do this)

Inhibitory postsynaptic potential (IPSP) – the postsynaptic membrane is
hyperpolarized as a result of presynaptic release of a neurotransmitter. A transmittergated ion channel opens and Cl- flows into the cell through it (glycine-gated or
GABA gated ion channels)
o
G-protein-coupled receptor – can be used by all 3 types of neurotransmitters. Results in
slower, longer-lasting, and much more diverse postsynaptic actions. Metabotropic receptors.
Basically can have two results – open a channel, or activate and enzyme to make secondary
messangers

Steps

1. Neurotransmitter binds to receptor proteins embedded in postsynaptic
membrane

2. Recpetor protein activates small G-Proteins, that are free to move along
the intracellular face of the postsynaptic membrane

3. The activated G-Proteins will active “effector” proteins

Effector proteins can be G-protein-gated ion channels in the
membrane or enzymes that synthesize secondary messengers.
o
Second messenger – diffuse away in the cytosol and
activate additional enzymes that can regular ion channel
function and alter cellular metabolism.

Metabotropic receptor – receptors that can trigger widespread metabolic effects

*The same neurotransmitter can have different effects on different cells because of
the different postsynaptic receptor proteins.

Autoreceptor – presynaptic neurotransmitter receptor proteins. Activation of these
(usually g-protein-coupled receptor proteins) usually will inhibit neurotransmitter
release, or stimulate the production of more of a certain kind of neurotransmitter.
This allows a presynaptic terminal to regulate itself; feedback inhibition.

Neurotransmitter Recovery and Degradation
o
Neurotransmitters can diffuse away from the synapse, or neurotransmitter transporter proteins
in the presynaptic membrane will suck them back in. Once inside the cytosol, they can be
enzymatically destroyed or packed back up into synaptic vesicles. Glia surrounding the
synapse also aid in the removal of neurotransmitters from the cleft. Enzymatic destruction can
also occur at in the cleft itself.
o
Removal is key – if not, some channels may no longer be sensitive to its neurotransmitter. As
a result, it doesn’t work anymore. This is how many poisionous gases work.

At the neuromuscular junction, high concentrations of ACh after several seconds
leads to a process called desensitization – basically the transmitter-gated channels
close despite the continued presence of ACh. Usually, the destruction of ACh by
AChE will prevent this, but if AChE is inhibited, the ACh receptors will become
desensitized and neuromuscular transmission will fail.

Neuropharmacology – the study of the effects of drugs on the nervous system tissue
o Inhibitor – one class of drug action wherein the drug inhibits the normal function of specific
proteins involved in synaptic transmission

Receptor antagonist – inhibitors of neurotransmitter receptors. Bind to the receptors
and block (antagonize) the normal action of the transmitter.
o
Receptor agonist – a second class of drug action wherein the drug mimics the actions of the
naturally occurring neurotransmitter (eg, nicotine activates the ACh receptors in skeletal
muscle)

Nicotinic ACh receptor – the ACh-gated-ion channels in muscle (this is to
distinguish them from other types of ACh receptors, such as those in the heart as
these are not activated by nicotine)
Principles of Synaptic Integration

Synaptic integration – the process by which multiple synaptic potentials combine within one
postsynaptic neuron

The Integration of EPSPs (Excitatory Postsynaptic Potential)
o Elementary unit of neurotransmitter release is the contents of a single synaptic vesicle
(usually they all have about the same number in them). EPSPs at a given synapse are
quantized; they are multiples of an indivisible unit, the quantum, that reflects the number of
transmitter molecules in a single synaptic vesicle and the number of postsynaptic receptors
available.
o
Miniature postsynaptic potential – usually just called a “mini. Amount of EPSP generated by
the transmitter contents of one vesicle. Therefore, the amplitude of the postsynaptic EPSP is
just an integer multiple of the mini amplitude.
o
Quantal analysis – method of comparing amplitudes of minis and evoked postsynaptic
potentials (caused by the released of hundred to thousands of vesicles) to determine just how
many vesicles were released during normal synaptic transmission.

Example: neuromuscular junction  one action potential triggers exocytosis of
about 200 synaptic vesicles, causing an EPSP (change in membrane potential of the
postsynaptic membrane) of 40 mV or more. At many CNS synapses however, an AP
will cause the exocytosis of only a single vesicle, cause an EPSP of only a few tenths
of a millivolt
o
EPSP summation – the simplest form of synaptic integration in the CNS.

Spatial summation – the adding together of EPSPs generated simultaneously at many
different synapses on a dendrite

Temporal summation – adding together of EPSPs generated at the same synapse, if
they occur within rapid succession (~ 1-15 msec)

The current entering at the sites of synaptic contact must spread down the dendrite,
through the soma, to the spike-initiation zone to be depolarized beyond threshold
before an action potential can be generated. Many dendrites have many voltagegated sodium channels, however. As a result, EPSPs flowing down would open some
of these channels. This will add to the electrical current, allowing the synaptic signal
to “stay alive” longer.


Length constant – the distance where depolarization is 37% of that at the origin. This is dependent on
two factors
o
Internal resistance – the resistance to current flowing longitudinally down the dendrite
o
Membrane resistance – the resistance to current flowing across the membrane
Inhibition – the difference between the postsynaptic receptors of inhibitory synapses and regular
synapses is this small. Both synapses use transmitter-gated ion channels, however, inhibitors bind
different neurotransmitters (GABA and glycine) and they allow different ions to pass through their
channels – usually Cl -. Cl- will try to bring the membrane potential to -65mV, if it isn’t already there.
o
Shunting inhibition – activation of the excitatory synapse leads to influx of positive charge. It
will flow down the membrane toward the soma. At the site of the inhibitory synapse, the
membrane potential is ~ -65mV. Positive current will therefore fly outward across the
membrane. This synapse acts as an electrical shunt, preventing the current from flowing from
dendrite to the soma. This is shunting inhibition. The actual physical basis of this is the
inward movement of negatively charged chloride ions, which is equivalent to outward positive
current flow.


These are especially concentrated in the soma and near the axon hillock.
Modulation – synaptic activation wherein receptors do not directly evoke EPSPs or IPSPs, but instead
modifies the effectiveness of EPSPs generated by other synapses. This type of synapse does not use
ion channels, but does use G-protein-coupled receptors.
o
Examples

Binding of the amine neurotransmitter norepinephrine (NE) to receptors. This sets
off a cascade of events.

Receptros activate a g-protein which activates and effector protein adenylyl cyclase. This enzyme converts ATP into cAMP (secondary
messanger).

cAMP triggers protein kinases to catalyze phosphorylation – the addition of
phosphate groups from ATP to sites on cell proteins. This causes a
conformational change in a protein, thereby changing that protein’s activity.

In some neurons, one of the phosphorylated proteins is a potassium channel in the
dendritic membrane, thereby reducing K+’s conductances. This increases the
dendritic membrane’s resistance and therefore increases the length constant.
Neurotransmitter Systems
9/2/2015 1:25:00 AM
Introduction

Neurotransmitter System (three classes: amino acids, amines, and peptides) – the molecule, all the
molecular machinery responsible for transmitter synthesis, vesicular packaging, reuptake and
degradation, and transmitter action.
o
Cholinergic – a word used to describe the cells that produce and release acetylcholine.
o
Noradrenergic - a word used to describe the cells that produce and release norepinephrine.
o
Glutamatergic - a word used to describe the synapses that produce and release glutamate.
o
GABAergic – a word used to describe the synapses that produce and release GABA.
o
Peptidergic – a word used to describe the synapses that produce and release peptides.
o
*These are also used to describe the various neurotransmitter systems. Ex: cholinergic system
Studying Neurotransmitter Systems

What defines a neurotransmitter?
o 1. The molecule must be synthesized and stored in the presynaptic neuron

Methods used to show this include immunocytochemistry and in situ hybridization

Immunocytochemistry: basically, inject the neurotransmitter molecule into
the bloodstream – this produces an immune response. Antibodies form, and
they bind tightly to the transmitter of interest. These antibodies are removed
and chemically tagged, then applied to a section of brain tissue. They will
color just those cells that contain the transmitter candidate. This method can
also be used to tag the synthesizing enzymes for transmitter candidates. If it
is found that both and enzyme and transmitter candidate are contained in the
same neuron – or axon terminal – then it can help show that the molecules
satisfies this first requirement.

In Situ Hybridization: a probe (strand of RNA complimentary to the
mRNA that codes for a certain polypeptide/protein) is chemically labeled,
and applied to a section of brain tissue. Neurons that contain the label
contain the mRNA that codes for that protein or polypeptide. The probes are
usually labeled by making them radioactive.

Autoradiography is used to detect radioactive probes – brain tissue
is put on a special sheet of film that is sensitive to radioactive
emissions.
o
2. The molecules must be released by the presynaptic axon terminal upon stimulation

In some cases (mostly in the peripheral nervous system), a specific set of neurons
can be stimulated while taking samples of the fluid surrounding their synaptic targets.
Then this sample can be used to see if it creates a synaptic response similar to those
of intact synapses. Then the sample can be chemically analyzed to determine the
structure of the active molecule (this is how ACh passed stage 2). This doesn’t work
in the CNS because there are so many intertwining axons and transmitters.

In the CNS, researches have to stimulate many synapses in a brain region and then
collect and measure all chemicals that are released. Use brain slices that are kept
alive in vitro. Slices bathed in K+ solution, causing depolarization. Also, must be
shown that the transmitter candidate is not released when Ca2+ isn’t present. Even
still, its not certain that the chemicals released were from the terminals – could have
been released as a secondary consequence of synaptic activation. Step 2 is the
hardest to satisfy (especially in the CNS).
o
3. The molecule must evoke the same response as that produced by the release of naturally
occurring neurotransmitter from the presynaptic neuron

Microionophoresis – neurotransmitter candidates are dissolved in solutions that
cause them to acquire a net electrical charge. Put into a pipette, which slowly injects
little bits of transmitter candidate right next to the synapse. Then a microelectrode in
the postsynaptic neuron measures the effects on the membrane potential.

If this causes electrophysiological change that mimics the effects of transmitter
released at the synapse (and criterion 1 and 2 are satisfied), then the molecule and
transmitter are usually considered to be the same chemical.

Studying Receptors
o No two neurotransmitters bind to the same receptor. However, one neurotransmitter can bind
to many different receptors. Each of the different receptors a neurotransmitter binds to is
called a receptor subtype.
o
Three methods are used to study the difference receptor subtypes of the various
neurotransmitter systems: neuropharmacological analysis, ligand-binding methods, and
molecular analysis of receptor proteins

Neuropharmacological Analysis – studying how different drugs affect the different
subtypes is used: nicotine is a receptor agonist in skeletal muscle, but has no effect in
the heart. Muscarine (mushroom poison) has no effect on skeletal muscle, but is an
agonist (binds in the place of ACh and slows the heart to the point of death) at the
cholinergic receptor subtype in the heart. Use of selective antagonists is also used
(curare at ACh nicotinic receptors and atropine at ACh muscarinic receptors).

Difference drugs were used to distinguish subtypes of glutamate receptors –
which mediate much of the synaptic excitation in the CNS.

AMPA Receptor, NMDA Receptor, and Kainate receptors, each
named for a different chemical agonist, are three subtypes of
glutatonic receptors.

Ligand-Binding Methods – technique of studying receptors using radioactively
labeled ligands. Ligands are chemical compounds that bind to a specific site on a
receptor. This method was used to isolate neurotransmitter receptors and determine
their chemical structure. Discovered by the study of opiates.

Molecular Analysis – molecular analysis is the most recent method and has given the
appreciation of the massive complexity of receptor subtype diversity.
Neurotransmitter Chemistry

Most of the known neurotransmitter molecules are either (1) amino acids, (2) amines derived from
amino acids, or (3) peptides constructed from amino acids. ACh is an exception, but is made from
acetyl CoA, which is a byproduct of cellular metabolism
o
Dale’s Principle – The idea that a neuron has only one neurotransmitter

Usually not true of peptide-containing neurons

Co-Transmitter – when two or more transmitters are released from one nerve
terminal, they are called co-transmitters

Cholinergic Neurons
o Acetylcholine – the neurotransmitter at the neuromuscular junction, and therefore synthesized
by all the motor neurons in the spinal chord and brain stem.
o
Choline Acetyltransferase (ChAT) is the enzyme that makes ACh by combining Choline
(which exists in the extracellular fluid in low concentrations) and Acetyl CoA. ChAT makes
ACh, then a transporter concentrates it into a vesicle.

Because the availability of choline limits how much ACh can be synthesized, the
transport of choline into the neuron is said to be the rate-limiting step in ACh
synthesis.

o
Nicotonic ACh receptors – skeletal muscle
o
Muscarinic ACh receptors – cardiac muscle
Catecholaminergic Neurons
o The amino acid tyrosine is the precursor for three different amine neurotransmitters that
contain a chemical structure called a catechol. These neurotransmitters are collectively called
catecholamines.
 Catecholamine neurotransmitters include dopamine (DA), norepinephrine (NE), and
epinephrine (aka adrenaline).

Found in regions of the nervous system involved in movement, mood,
attention, and visceral (non-voluntary) function

Tyrosine hydroxylase catalyzes the first step in catecholamine synthesis –
converting tyrosine to a compound called dopa.

The activity of TH is rate-limiting for catecholamine synthesis.
Feedback inhibition keeps TH in check.

Tyrosine  Dopa  Dopamine  Norepinephrine  Epinephrine
o There are enzymes on each arrow that facilitate the
change.

The actions of catecholamine neurotransmitters are terminated by the
selective uptake of the NTs back into the axon terminal via Na + dependent
transporters (no AChE equivalent for these NTs).

The catecholamines may be enzymatically destroyed by the action of
monoamine oxidase (MAO), an enzyme found in the outer membrane of
mitochondria.

Serotenergic Neurons
o Amine neurotransmitter serotonin (5-HT) is derived from the amino acid tryptophan.

Serotonergic neurons are few in number, but play important roll in mood, emotional
behavior, and sleep.

Serotonin is created similar to dopamine. Tryptophan  5-HTP  5-HT
 Rate-limiting factor is the availability of tryptophan in the extracellular
fluid bathing the neurons – tryptophan comes from the diet.


5-HT is removed from the cleft via a specific transporter.
Amino Acidergic Neurons
o Amino acids Glu, Gly, gamma-amniobutyric acid (GABA) are the neurotransmitters at most
CNS synapses.
o
Glutamatergic cells therefore just have a higher concentration of Glu, because Glu exists in all
cells (as it is among the 20 amino acids that compose proteins). Transporters are the big
difference btween glutagatergic and nonglutamatergic cells – because this transporter can
concentrate glutamate until it reaches a value of about 50mM in synaptic vesicles.
o
GABA is not one of the 20 amino acids that make up proteins – it is only synthesized by the
cells that need it. GABA is synthesized by glutamic acid decarboxylase (GAD) and so it’s a
good marker for GABAergic cells. GABAergic neurons are the major source of synaptic
inhibition in the nervous system.
o
Synaptic action is terminated by the selective uptake into presynaptic treminals and glia via
Na+ dependent transporters. GABA is metabolized once back inside the cell by GABA
transaminase.

Other Neurotransmitter Candidates and Intercellular Messengers
o ATP- Few other small molecules act as chemical messengers between neurons – such as ATP.
ATP is usually packaged in vesicles with another classic transmitter.

ATP binds to purinergic receptors – some are transmitter-gated ion channels, some
are G-protein-coupled purinergic receptors.
o
Endocannabinoids: New discovery – small lipid molecules, called endocannabinoids – are
released from postsynaptic to presynaptic terminals. Communication in this direction is called
retrograde signaling – endocannabinoids therefore are called retrograde messengers.

Bascially, repeated firing of action potentials in a postsynaptic neuron causes
elevated Ca2+ which prompts synthesis of endocannabinoid molecules from
membrane lipids. Unusual qualities about endocannabinoids:

They are not packaged in vesicles; instead they are manufactured rapidly
and on-demand

They are small and membrane permeable; once synthesized, they diffuse
rapidly across the membrane of their cell to contact neighboring cells

They bind selectively to the CB1 type o cannabinoid receptor, which is
mainly located on certain presynaptic terminals.

CB1 receptors are g-protein-coupled; main effect is to reduce opening of presynaptic
calcium channels.
o
Nitric Oxide: NO is membrane permeable and small, suggesting it may also be a retrograde
messenger. Powerful effects especially in the regulation of blood flow. It can even pass
through one cell to get to another on the other side. But it does break down very rapidly.

*Should be noted that NTs aren’t specific to neurons – they can also exist in different parts of the body
and have different effects in these parts.
Transmitter-Gated Channels

Channels are sensitive detectors of chemicals and voltage, regulate the slow of surprisingly large
currents, and sift between various similar ions. It can be regulated by other receptor systems. Very
versatile.
o
Basic Structure of Transmitter-Gated Channels

ACh: five protein subunits form a pore. Two ACh must bind to the two alpha
subunits, and this opens the channel. Each subunit polypeptide has 4 segments that
coil into alpha helixes. These helixes are hydrophobic, and so are probably the part
in the membrane. Most channels are thought to be similar in structure to the nicotinic
ACh receptor described above.

o
Glutamate receptors are different – four subunits that form the channel.
Amino Acid-Gated Channels

Mediate most fast synaptic transmission in the CNS. These are the properties that
distinguish them from one another and define their function

Pharmachology of their binding sites describes the transmitters that bind to
them and how drugs impact them

Kinetics of the transmitter binding process and channel gating determine the
duration of their effect

Selectivity of the ion channels determines whether they produce excitation
or inhibition, and whether Ca2+ enters the cell in significant amounts


Conductance of open channels help determine the magnitude of their effects.
Glutamate-Gated Channels

AMPA (named after the selective agonist) gated channels are permeable to
potassium and sodium, but not calcium. When they open, rapid and large
depolarization occurs. AMPA receptors therefore mediate excitatory
transmission in the CNS.

NMDA-gated channels also cause excitation by admitting sodium – differ
from AMPA because (1) are permeable to Ca2+ and (2) inward current
through them is voltage dependent.

1. When the channel opens, sodium and calcium flood inward

2. In order for these ions to flood in, the cell must be depolarized
already. At normal negative potential, the channels become
clogged with Mg2+, in an event called magnesium block. Thus,
ionic current through these channels is voltage dependent.


*Both glutamate and depolarization must coincide before the
channel will pass current
GABA-Gated and Glycine-Gated Channels

GABA responsible for most synaptic inhibition in the cell. Inhibition must
be tightly regulated, so this is why the GABA channels have many other
sites on it for other chemicals to modulate its function. Benzodiazepine and
Barbiturates are two classes of drugs that bind to the channel. When these
drugs are bound to the channel at the same time as GABA, it increases the
duration or frequency of channel openings, resulting in more inhibitory Cl current, therefore stronger IPSPs.

Glycine mediates most of the rest of synaptic inhibition (not in the CNS)
G-Protein-Coupled Receptors and Effectors – Multiple subtypes of G-protein-coupled receptors in every known
transmitter system.

The Basic Structure of G-Protein-Coupled Receptors
o Simple variation on a common plan: single polypeptide containing 7 alpha helices.
Extracellular loops of the polypeptide bind neurotransmitters, intracellular loops bind gproteins
o
The Ubiquitous G-Proteins (Guanosine triphosphate binding protein) – about 20 types, but all
have the same MO

1. Each G-Protein has 3 subunits – alpha, beta, and gamma. In resting state, GDP is
bound to Ga and the whole complex floats around inner surface of the membrane

2. If this at rest protein bumps into the proper type of receptor and if that receptor has
the transmitter molecule bound to it, the G-protein exhanges the GDP for a GTP
(from the cytosol)

3. Activated protein splits into two parts: alpha subunit plus GTP, and beta-gamma
complex. Both then move to influence various effector proteins

4. Ga is an enzyme that eventually terminates its own activity by converting GTP to
GDP


5. The alpha complex and beta-gamma complex come together, restarting the cycle
G-Protein-Coupled Effector Systems
o The shortcut pathway – g-protein-gated ion channels

Ex: muscarinic receptors in the heart  ACh receptors bind to ACh and g-protein,
then the G-protein is activated and goes and opens a K+ channel. This slows
depolarization (the heart rate, in this scenario).

o
This pathway is faster, but localized.
Second Messenger Cascade – G-protein activates certain enzymes. These enzymes activate
other enzymes via second messengers and so on.

This results in widespread effects. Activation of adenylyl cyclase will cause a rise of

cAMP  this activates protein kinase A.
Signal can be amplified. For example, activation of G-proteins can stimulate
phospholipase C (PLC) which splis a membrane phospholipid creating two
molecules that serve as secondary messengers (Diacylglycerol, DAG and Inositol – 1,
4, 5 – triphosphate, IP3). DAG activates protein kinase C. IP3 binds to channels in
organelles, causing them to dispel Ca2+. This calcium activates CalciumCalmodulin-Deptendent Protein Kinase (CaMK), which is implicated in the
molecular mechanisms of memory.
o
Phosphorylation and Dephosphorylation

Key downstream enzymes are usually protein kinases – proteins that transfer
phosphate from ATP in the cytosol to proteins. Phosphorylation of ion channels for
example can influence the probability that they will open or close.

Enzymes called protein phosphatases rapidly remove these phosphate groups.
Phosphatases dephosphorylate proteins.
o
Function of Signal Cascades

Why? They are slow and complex compared to transmitter-gated ion channels, but
signal amplification. The use of small messengers such as cAMP also allows
signaling over a distance. Finally, signal cascades can generate long-lasting chemical
changes in cells, which may form the basis for memory.
Divergence and Convergence in Neurotransmitter Systems

One neurotransmitter can activate more than one subtype of receptor, and cause more than one
postsynaptic response – this is called divergence. This can occur at any point along the cascade.

Neurotransmitters can also exhibit convergence, in which many NTs and receptors can converge to
affect the same effector systems.

Neurons integrate divergent and convergent signaling in a complex map of chemical effects.
The Structure of the Nervous System
Alec Jotte
Gross Organization of the Mammalian Nervous System

Two divisions: Central Nervous System (CNS) and Peripheral Nervous System (PNS)

Anatomical References
o Rostral or Anterior: towards the nose
o
Caudal or Posterior: towards the tail
o
Dorsal: pointing up
o
Ventral: pointing down

Bilateral Symmetry: right and left sides are mirrors of each other – this is the case for
most of the nervous system
o
Midline: invisible line running down the middle of the nervous system
o
Medial: structures closer to the midline
o
Lateral: structures farther away from the midline
o
Two structures on the same side of the midline are ipsilateral to each other
o
Two structures on opposite sides of the midline are contralateral to each other
o
Anatomical Planes of Section


A slice of brain is called a section. To slice is to section.

Midsagittal Plane: belly button to nose direction. Sagittal plane. Right/left halves

Horizontal Plane: parallel to the ground. Dorsal/ventral parts

Coronal Plane: perpendicular to the ground. Anterior/postier parts
The Central Nervous System
o CNS consists of the brain and spinal cord. Three parts are common to all mammals: cerebrum,
cerebellum, and the brain stem.

The Cerebrum: the rostral-most and largest part of the brain. Clearly split down the
middle into two cerebral hemispheres by the sagittal fissure. Right hemisphere
controls left body and left hemisphere controls right body.

The Cerebellum: lies behind the cerebrum (“little brain”). Responsible for
movement control. Left side controls left side and right side controls right side.

The Brain Stem: the stalk from which the cerebrum/cerebellum sprout – relays
information from spinal cord  cerebrum/cerebellum and vice versa. Also the site
where vital function are regulated.

Spinal Cord: major receptor of information from the skin, joints, and muscles of the
body to the brain, and vice versa. Spinal cord communicates to body via spinal
nerves – part of the peripheral nervous system.

Spinal nerves attach between vertebrate, and each one attaches by means of
two branches – dorsal root (brings information in) and ventral root
(carries information out).

The Peripheral Nervous System
o PNS consists of the nervous system other than the brain and spinal cord

o
PNS has two divisions – the somatic PNS and visceral PNS.
The Somatic PNS – spinal nerves that innervate skin, joints, and the muscles that are under
voluntary control. Somatic motor axons (PNS) derive from motor neurons in the spinal cord
(CNS) and carry info via the ventral roots.

Somatic sensory axons – collect info from skin, joint, muscles – enter spinal cord
via dorsal roots. The cell bodies of these neurons lie just outside the spinal cord and
are called dorsal root ganglia.
o
The Visceral PNS (aka Autonomic Nervous System or ANS) – consists of neurons that
innervate internal organs, blood vessels, and glands. Bring info about visceral function to the
CNS, such as pressure and O2 content of blood in arteries.
o
Afferent (“carry to”) vs efferent (“carry from”) neurons. Relative terms. Afferent means
carrying information towards, efferent means carrying information away from.

Cranial Nerves – 12 pairs that arise from the brain stem and innervate (mostly) the head. Some are a
part of the CNS, others the somatic PNS, others the visceral PNS.

The Meninges – the CNS doesn’t come in direct contact with the overlaying bone – it is protected by
3 membrane layers called the meninges.
o
Dura mater (“tough mother”) – outermost covering that forms a touch, inelastic bag that
surrounds the brain and spinal cord.
o
Arachnoid membrane – lies just underneath the dura mater. If blood vessels passing through
the dura rupture, blood can collect here and form a subdural hematoma. This can cause
pressure that disrupts the actions of the CNS.
o
Pia mater (“gentle mother”) – thin membrane that adheres closely to the surface of the brain.
The Pia is separated from the arachnoid membrane by a subarachnoid space filled with fluid
called cerebrospinal fluid (CSF).

The Ventricular System
o The fluid filled caverns and canals inside the brain constitute the ventricular system. This
fluid is CSF.
o
CSF is produce by a special tissue called the choroid plexus, in the ventricles of the cerebral
hemispheres.

Imaging the Living Brain
o Computed Tomography (CT Scan) – an x-ray source is rotated around the head within the
plane of the desired cross section. It develops an image of the brain.
o
Magnetic Resonance Imaging (MRI) – slowly replacing CT scans because it yields a much
more detailed map of the brain than does CT, and with more flexibility. Has to do with how
hydrogen in the head reacts to a strong magnetic force
o
Fuctional Brain Imagine – 2 methods

Positron emission tomography (PET Scan) and functional magnetic resonance
imaging (fMRI) – basically detect changes in blood flow to show which parts of the
brain are active under different circumstances
Understanding CNS Function Through Development

Terms that you need to know
o Collections of Neurons

Gray matter – generic term for collection of neuronal cell bodies in the CNS

Cortex – any collection of neurons that form a thin sheet, typically at the brain’s
surface.

Nucleus – clearly distinguishable mass of neurons, usually deep in the brain

Substantia – a group of related neurons deep within the brain  less strict and
distinct than nuclei (substantia is neurons responsible for voluntary movement,
nucleus is neurons responsible for voluntary movement of the eye)

Locus – a small, well-defined group of cells

Ganglion – a collection of neurons in the PNS.

Exception, basal ganglia which lie deep in the cerebrum and control
movement
o
Collections of Axons

Nerve – bundle of axons in the PNS. Only one collection of CNS axons is called a
nerve – this is the optic nerve.

White matter – a generic term for a collection of CNS axons

Tract – collection of CNS having a common site of origin and common destination

Bundle – collection of axons that run together but do not necessarily have the same
origin and destination


Capsule – a collection of axons that connect the cerebrum with the brain stem

Commissure – any collection of axons that connect one side of the brain to the other

Lemniscus – A tract that meanders through the brain like a ribbon
Formation of the Neural Tube
o Embryo begins as a flat disk with three distinct layers of cells – endoderm, mesoderm, and
ectoderm.
o

Endoderm gives rise to linins of many internal organs (viscera)

Mesoderm gives rise to the bones of the skeleton and the muscles

Ectoderm gives rise to the nervous system and the skin
Ectoderm – the neural plate. The brain consists of a flat sheet of cells.

Groove forms in the neural plate that runs rostral to caudal – neural groove.

The walls of the groove are called neural folds. These will fuse and form the neural
tube. This process is called neurulation.

*The entire CNS develops from the walls of the neural tube.

As neural tube forms, some neural ectoderm tissue is pinched off, and ends up just
next to the neural tube on either side. This is the neural crest, *and all cells with cell
bodies in the PNS derive from the neural crest
o
Mesoderm – develops bulges on either side of the neural tube called somites. From these, the
entire vertebrate and related skeletal muscles will develop. The nerves that innervate these
skeletal muscles are therefore called somatic motor neurons

Three Primary Brain Vesicles
o The first step in brain differentiation is the development of three swellings called primary
vesicles at the rostral end of the neural tube. The entire brain comes from the three primary
vesicles of the neural tube.


Prosencephalon (forebrain) – rostral most vesicle

Mesencephalon (midbrain) – just caudal to the prosencephalon

Rhombencephalon (hindbrain) – caudal to the mesencephalon
Differentiation of the Forebrain
o Secondary vesicles sprout off both ends of the
prosencephalon. These are the optic vesicles
and the telencephalic vesicles. The unpaired
middle section that remains is called the
diencephalon.
o
The optic vesicles grow and fold in to
eventually form the optic nerves and retinas in
the adult
o
Differentiation of the Telecephalon and
Diencephalon

The telencephalic vesicles together
form the telencephalon. Another pair of vesicles sprout off the ventral surfaces of
the cerebral hemispheres, giving rise to the olfactory bulbs.

The fluid filled spaces within the cerebral hemispheres are called the lateral
ventricles, and the space at the center of the diencephalon is called the third
ventricle.

Two types of gray matter form in the telencephalon:

Two types of gray matter form in the diencephalon:



Cerebral cortex and the basal telencephalon
Thalamus and the hypothalamus
Three Major White Matter Systems in the Forebrain

Cortical White Matter – contains all the axons that run to and from the
neurons in the cerebral cortex

Corpus Callosum – axons that connect the two hemispheres

Internal Capsule – axons that links the cortex with the brain stem,
particularly the thalamus
o
Forebrain Structure-Function Relationships

Somatic sensation relays in the thalamus en route to the cortex

Information is carried back and forth from either hemisphere via the corpus callosum

Damage to basal ganglia disrupts voluntary movement ability

Hypothalmus – performs many primitive unctions. Controls the ANS.
Increases/decreases heart rate, controls fight or flight, etc. Key in motivating animals
to find food, drink, and sex in response to their needs.

Differentiation of the Midbrain
o The dorsal surface becomes the tectum and the floor becomes the tegmentum. The CSFfilled space in between the two is a tight narrow channel called the cerebral aqueduct and
connects the third ventricle of the diencephalon to the fourth ventricle.
o
Mid-Brain Structure-Function Relationships

Serves as a conduit for info passing from spinal cord to forebrain and vice versa. It
also helps control sensory systems and movement. The corticospinal tract courses
through the midbrain, and damage on one side produces a loss of voluntary control
of movement on the opposite side of the body.


The tectum differentiates into two sections

Superior colliculus – receives direct input from the eye. Controls
eye movement

Inferior colliculus – receives direct input from the ears. Important
relay station for auditory info en route to the thalamus
Differentiation of the Hindbrain
o Three Important Structures in Two Categoriees


Metencephalon (Rostral half of hindbrain)

The Cerebellum

The Pons
Myelencephalon (caudal half of hindbrain)

The Medulla

Medullary pyramids – bundles of axons headed towards the spinal
cord
o
The CSF filled tube becomes the fourth ventricle.
o
Hindbrain Structure-Function Relationships

Processing sensory info, control of voluntary movement, and regulation of ANS.

Cerebellum receives massive input from spinal cord and pons. Pons relay info from
the cerebral cortex. Spinal cord relays info from the body.

Pons are critical – sort and relay info from the cerebral cortex to the cerebellum.

When the medulla joins the spinal cord, each pyramidal tract crosses the midline,
forming the pyramidial decussation.

Medulla also has neurons that perform sensory and motor functions –
auditory nerves synapse in the medulla, touch and taste the same.

Differentiation of the Spinal Cord
o As tissue expands in the walls of the caudal neural tube, the cavity constricts and forms the
tiny CFS-filled spinal canal.
o
Spinal gray matter forms a butterfly shape  dorsal horn and ventral horn with an
intermediate zone in the middle.
o
Spinal Cord Structure-Function Relationships

Dorsal horn cells receive sensory inputs from dorsal root fibers

Ventral horn cells project axons into the ventral roots that innervate muscles

Intermediate zone cells are interneurons that shape motor outputs based on sensory
inputs.

Dorsal column carries sensory info to the brain.

Lateral column has axons in the corticospinal tract (pyramidal tract) that
communicate voluntary movement signals.

Neurons of spinal cord begin analysis of sensory info, play a role in coordinating
movements, and work simple reflexes (jerking foot off of thumbtack)

Putting the Pieces Together
o The diencephalon surrounds the third ventricle
o
The midbrain surrounds the cerebral aqueduct
o
The cerebellum, pons, and medulla surround the fourth ventricle
o
The grooves on the human brain are called sulci and the bumps are called gyri. These allow
increased surface area (i.e., more neurons, as the gray matter is only a thin sheet) without
increasing the volume too much.
o
The cerebral cortex is partitioned

Temporal Lobe is on the sides just under the temples

Frontal Lobe is just under the frontal bone of the forehead

Parietal Lobe just caudal to the central sulcus which separates the frontal lobe from
the parietal lobe

Occipital Lobe caudal to the parietal lobe at the very back of the cerebrum
A Guide to the Cerebral Cortex

Types of Cerebral Cortex
o Cell bodies of cortical neurons are parallel to the surface of the brain. Layer of neurons closest
to the surface is separated from the pia mater by a zone that lacks neurons  called molecular
layer, or layer 1. At least 1 cell layer contains pyramidal cells that emit large dendrites called
apical dendrites, that extend into layer I, where they form multiple branches.
o
Hippocampus – has only a single cell layer. Section of cortex that is between the lateral
ventricle and the midline. The olfactory cortex is connected to this, and has 2 cell layers.
o

There is one more cortex, called the neocortex – the neocortex is found only in mammals.
Areas of Neocortex
o Broadmann constructed a cytoarchitectural map of the neocortex. Each cortical area
performs different functions.

Neocortical Evolution and Structure-Function Relationships
o Primordial neocortex consisted mainly of three types of cortex

The size of the neocortex has changed drastically. Also, the number of areas that are
“unassigned” in the human brain are much greater than in other animals.