Lecture 3: Biological Basis of Behavior 1

Cell Staining
Since neurons are very very small, the field of neurobiology did not truly begin until there were good enough
microscopes to see neurons. The field was also slow to begin because of the difficulty of harvesting neurons.
The consistency of the brain is much like Jello and it was not until the discovery of formaldehyde (which is
used to harden the structure of the brain) was it possible to cut the brain into small slices for study. These
technologies allowed for the field of histology to begin. Histology is the microscopic study of the structure
of tissues. One problem still remained after the start of histology. Freshly prepared brain has a uniform,
cream-colored appearance under the microscope and structures are impossible to make out. This was solved
with the invention of staining techniques.
Nissl Stain: Invented by German neurologist Franz Nissl in the late nineteenth century. The Nissl stain
can use a variety of dyes (cresyl violet, thionine, toluidin blue O, or methylene blue to name a few) and
selectively stains cell nuclei and surrounding nuclear structures.
Golgi Stain: Invented by Italian histologist Camillo Golgi in 1873. The Golgi stain consists of soaking brain
tissue in a silver chromate solution. This causes a small percentage of neurons to become darkly colored in
their entirety. This allows for the ability to look at a neuron’s entire structure.
Santiago Ramon y Cajal was a histologist and artist that used Golgi’s stain to work out the circuitry of many
regions of the brain. Ironically, Golgi and Cajal drew completely opposite conclusions about neurons. Golgi
supported the view that the neurites of different cells are fused together to form a continuous network similar
to arteries and veins. Cajal on the other hand said that the neurites are not continuous with one another
and must communicate by contact, not continuity. Cajal is right. The concept that neurons communicate
with each other by contact rather than continuity is known as the neuron doctrine. Although Golgi and
Cajal both shared the Nobel Prize in 1906, they remained bitter rivals to the end.

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The Prototypical Neuron

Soma: Otherwise known as the cell body. The soma is about 20µm in diameter and filled with the cell’s
organelles that are suspended in cytosol(a salty potassium rich solution).
Nucleus: Contains most of the cell’s genetic material, organized as multiple long linear DNA molecules in
complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these
chromosomes are the cell’s nuclear genome. The function of the nucleus is to maintain the integrity of these
genes and to control the activities of the cell by regulating gene expression.
Ribosomes: functions in the expression of the genetic code from nucleic acid into protein, in a process
called translation. Ribosomes do this by catalyzing the assembly of individual amino acids into polypeptide
chains; this involves binding a messenger RNA and then using this as a template to join together the correct
sequence of amino acids. This reaction uses adapters called transfer RNA molecules, which read the sequence
of the messenger RNA and are attached to the amino acids.
Endoplasmic Reticulum: a network of tubules, vesicles and sacs that are interconnected. They may serve
specialized functions in the cell including protein synthesis, sequestration of calcium, production of steroids,
storage and production of glycogen, and insertion of membrane proteins. Smooth ER has no ribosomes while
rough ER has ribosomes on its surface.
Golgi Apparatus: a stack of membrane-enclosed disks in the soma that lies farthest from the nucleus that
does extensive post-translational chemical processing of proteins. It sorts certain proteins that are destined
for delivery to different parts of the neuron.
Mitochondria: sometimes described as ”cellular power plants” because they generate most of the cell’s
supply of adenosine triphosphate (ATP), used as a source of chemical energy.

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Protein Synthesis

Protein synthesis is the process whereby DNA encodes for the production of amino acids and proteins.
This process can be divided into two parts:
1. Transcription Before the synthesis of a protein begins, the corresponding RNA molecule is produced by
RNA transcription. One strand of the DNA double helix is used as a template by the RNA polymerase to
synthesize a messenger RNA (mRNA). This mRNA migrates from the nucleus to the cytoplasm. During this
step, mRNA goes through different types of maturation including one called splicing when the non-coding
sequences are eliminated. The coding mRNA sequence can be described as a unit of three nucleotides called
a codon.
2. Translation The ribosome binds to the mRNA at the start codon (AUG) that is recognized only by
the initiator tRNA. The ribosome proceeds to the elongation phase of protein synthesis. During this stage,
complexes, composed of an amino acid linked to tRNA, sequentially bind to the appropriate codon in mRNA
by forming complementary base pairs with the tRNA anticodon. The ribosome moves from codon to codon
along the mRNA. Amino acids are added one by one, translated into polypeptidic sequences dictated by
DNA and represented by mRNA. At the end, a release factor binds to the stop codon, terminating translation
and releasing the complete polypeptide from the ribosome.
Nucleotides are organic compounds that consist of three joined structures: a nitrogenous base, a sugar, and
a phosphate group. The most common nucleotides can be divided into two groups (purines and pyrimidines)
based on the structure of the nitrogenous base. The joined sugar is either ribose or deoxyribose. Nucleotides
are the structural units of RNA and DNA. The different types are Adenine, Guanine, Uracil, Thymine, and
Cytosine. When they chain in a particular way they create codons that are translated into particular amino
acids by the ribosomes of a cell.

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The Axon
The axon begins with a region called the axon hillock, which tapers to form the initial segment of the axon
proper. Two noteworthy features distinguish the axon from the soma:
1. No rough ER extends into the axon, and there are few, if any, free ribosomes.
2. The protein composition of the axon membrane is fundamentally different from that of the soma mem-
brane.
The structural differences translate into functional distinctions. Because there are no ribosomes, there is no
protein synthesis in the axon. This means that all proteins in the axon must originate in the soma. And it
is the different proteins in the aconal membrane that enable it to serve as the “telegraph wire” that sends
information over great distances. The thickness of axons vary resulting in the effect that thicker axons have
faster impulse travel speed.
All axons have a beginning, a middle, and an end. The end is called the axon terminal or terminal
bouton, reflecting the fact that it usually appears as a swollen disk. The terminal is a site where the axon
comes in contact with other neurons (or other cells) and passes information on to them. This point of contact
is called the synapse. Sometimes axons have many branches at their ends and each branch forms synapses
at swollen regions along their length and then continue on to terminate elsewhere. Such swellings are called
boutons en passant. In either case, when a neuron makes synaptic contact with another cell, it is said to
innervate that cell, or to provide innervation. The cytoplasm of the axon terminal differs from that of the
axon in several ways:
1. Microtubules do not extend into the terminal.
2. The terminal contains numberous small bubbles of membrane, called synaptic vesicles, that measure
about 50nm in diameter.
3. The inside surface of the membrane that faces the synapse has a particularly dense covering of proteins.
4. It has numerous mitochondria, indicating a high energy demand.
Material is transported in vesicles down the axon to the axon terminal and back again through movement
along microtubules through the use of two different transport proteins. Kinesin provides anterograde trans-
port and dynein provides retrograde transport.

Dendrites
The dendrites of a single neuron are collectively called a dendritic tree with each branch being a dendritic
branch. The wide variety of shapes and sizes of dendritic trees are used to classify different groups of
neurons. Dendrites function as the antennae of the neuron - being covered with thousands of synapses. The
dendritic membrane under the synapse has many specialized protein molecules called receptors that detect
the neurotransmitters in the synaptic cleft. The internal makeup of dendrites is identical to that of axons
with the exception that ribosomes can exist in dendrites and proteins can be created in the dendrites.

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Glia
Most neuroscience research deals with neurons but recent study has shown that glia are also quite interesting.
Current evidence suggests that glia only play a supporting role in the way that our nervous system works
but some scientists believe that these cells may have more importance.

Astrocytes
The most numerous glia in the brain are astrocytes. These cells fill the spaces between neurons. Astrocytes
probably influence whether a neurite can grow or retract. An essential role of astrocytes is regulating the
chemical content of the extracellular space.

Myelinating Glia
Unlike astrocytes, the primary function of aligodendroglial and Schwann cells is clear. These glia provide
layers of membrane that insulate axons.

Microglia
Serves as phagocytes to remove debris left by dead or degenerating neurons and glia.

Ependymal Cells
Provide the lining of fluid filled ventricles within the brain.

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Resting Potential

Neurons send messages electrochemically. This means that chemicals cause an electrical signal. Chemicals
in the body are “electrically-charged”, when they have an electrical charge, they are called ions. The
important ions in the nervous system are sodium and potassium (both have 1 positive charge, +), calcium
(has 2 positive charges, ++) and chloride (has a negative charge, -). There are also some negatively charged
protein molecules. It is also important to remember that nerve cells are surrounded by a membrane that
allows some ions to pass through and blocks the passage of other ions. This type of membrane is called
semi-permeable.
When a neuron is not sending a signal, it is “at rest”. When a neuron is at rest, the inside of the neuron is
negative relative to the outside. Although the concentrations of the different ions attempt to balance out on
both sides of the membrane, they cannot because the cell membrane allows only some ions to pass through
channels (ion channels). At rest, potassium ions (K+) can cross through the membrane easily. Also at
rest, chloride ions (Cl-)and sodium ions (Na+) have a more difficult time crossing. The negatively charged
protein molecules inside the neuron cannot cross the membrane. In addition to these selective ion channels,
there is a pump that uses energy to move three sodium ions out of the neuron for every two potassium ions
it puts in. Finally, when all these forces balance out, and the difference in the voltage between the inside
and outside of the neuron is measured, you have the resting potential. The resting membrane potential of a
neuron is about -70 mV (mV=millivolt) - this means that the inside of the neuron is 70 mV less than the
outside. At rest, there are relatively more sodium ions outside the neuron and more potassium ions inside
that neuron.

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Action Potential

An action potential occurs when a neuron sends information down an axon, away from the cell body. The
action potential is an explosion of electrical activity that is created by a depolarizing current. This means
that some event (a stimulus) causes the resting potential to move toward 0 mV. When the depolarization
reaches about -55 mV a neuron will fire an action potential. This is the threshold. If the neuron does not
reach this critical threshold level, then no action potential will fire. Also, when the threshold level is reached,
an action potential of a fixed sized will always fire...for any given neuron, the size of the action potential is
always the same. There are no big or small action potentials in one nerve cell - all action potentials are the
same size. Therefore, the neuron either does not reach the threshold or a full action potential is fired - this
is the ”ALL OR NONE” principle.
Action potentials are caused by an exchange of ions across the neuron membrane. A stimulus first causes
sodium channels to open. Because there are many more sodium ions on the outside, and the inside of
the neuron is negative relative to the outside, sodium ions rush into the neuron. Remember, sodium has a
positive charge, so the neuron becomes more positive and becomes depolarized. It takes longer for potassium
channels to open. When they do open, potassium rushes out of the cell, reversing the depolarization. Also
at about this time, sodium channels start to close. This causes the action potential to go back toward -70
mV (a repolarization). The action potential actually goes past -70 mV (a hyperpolarization) because the
potassium channels stay open a bit too long. Gradually, the ion concentrations go back to resting levels and
the cell returns to -70 mV.

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The Synapse
The junction between the axon terminals of a neuron and the receiving cell is called a synapse. Action
potentials travel down the axon of the neuron to its end(s), the axon terminal(s). Each axon terminal is
swollen forming a synaptic knob. The synaptic knob is filled with membrane-bounded vesicles containing a
neurotransmitter. Arrival of an action potential at the synaptic knob opens Ca2+ channels in the plasma
membrane. The influx of Ca2+ triggers the exocytosis of some of the vesicles. Their neurotransmitter
is released into the synaptic cleft. The neurotransmitter molecules bind to receptors on the postsynaptic
membrane. These receptors are ligand-gated ion channels.
After a neurotransmitter is released and has conducted the impulse to the next cell or cells, it is either broken
down by enzymes or is absorbed back into the cell that released it in a process called reuptake.
The neurotransmitter at excitatory synapses depolarizes the postsynaptic membrane. The neurotransmitter
at inhibitory synapses hyperpolarizes the postsynaptic membrane. Some important neurotransmitters to
know are:
Acetylcholine: affects memory function, as well as muscle contraction, particularly in the heart.
Seratonin: related to arousal, sleep, pain sensitivity, mood, and hunger regulation.
Dopamine: associated with movement, attention, and reward; dopamine imbalances may play a role in
Parkinson’s disease and in schizophrenia.
GABA: an inhibitory neurotransmitter.