<p></p><p>The discovery
of neurotransmitters and the firing of the EEG were different discoveries. Hans
Berger was not the first electroencephalographer (Caton was), but Berger was
the first to dedicate time to studying the firing of the brain. Berger was
excessively self-conscious about his initial findings on EEG, so much so that
he undertook 5 years of testing and surveying the results of his studies on EEG
before he released it to the public in report form.&nbsp;</p><h3>Richard Caton (Left) and Hans Berger (Right)</h3><p>&nbsp;<img src="@@PLUGINFILE@@/berger.jpeg" alt="berger" width="444" height="333" class="img-responsive atto_image_button_middle"><img src="@@PLUGINFILE@@/caton.jpg" alt="caton" width="250" height="319" class="img-responsive atto_image_button_left"></p>

<p><br></p><h3>Otto Loewi</h3><img src="@@PLUGINFILE@@/Loewi.jpg" alt="loewi" width="180" height="255" class="img-responsive atto_image_button_left"><p>Otto Loewi was the
first neuroscientist to prove that neurotransmistters are released in the
junction (synapse) between the vagus nerve and the heart muscle. He received a
Nobel Prize with Henry Hallett Dale from Cambridge England in 1936 for their
discoveries. Loewi wrote:</p>

<p><i>The night
before Easter Sunday of that year, I awoke, turned on the light, and jotted
down a few notes on a tiny slip of thin paper. Then I fell asleep again. It
occurred to me at six o’clock in the morning that I had written down something
most important, but I was unable to decipher the scrawl. The next night, at
three o’clock, the idea returned. It was the experiment to determine whether or
not the hypothesis of chemical transmission that I had thought about years ago
was correct. I got up immediately, went of&nbsp;
the laboratory, and performed a simple experiment on a frog heart
according to the nocturnal design.</i> (Loewi, 1960, 15).</p><h2><a name="_Toc3535192"><br></a></h2><h3><a name="_Toc3535192">Ramon y Cajal and The Discovery of the Neuron</a></h3><p><a name="_Toc3535192">The neuron is considered to be the fundamental structural and functional unit of the nervous
system. While other organs of the body were fairly well understood morphologically during the
last few centuries, the understanding of what the neuron "looks like" was not well known until
early 1900. Before this time scientists could not "see" the structure of the brain and it appeared as
a tangled net of various fibers. In fact, several theories until the late 1800s held that the brain was
composed of a series of tiny tubes through which certain secretions flowed. Ill health was
thought to be the result of an imbalance of the flow of these secretions through these tubes.&nbsp;</a></p><p><a name="_Toc3535192"><img src="@@PLUGINFILE@@/cajal.png" alt="Cajal" width="300" height="370" class="img-responsive atto_image_button_left">Who first identified the structure of the neuron?
During the early years of 1900, a well known Spanish anatomist Santiago Ramon
y Cajal changed all that. Using a new staining method, silver chromate, recently
developed by his Italian colleague, Camillo Golgi, Cajal was able to identify the
structure and boundaries of individual neurons. It became evident to him that the
brain was composed of individual cells of varying morphologies and that these
cells were unique in several ways. First, neurons are not necessarily spherical
shaped as are cells of other body tissue. Indeed, there are several different forms
or morphologies to the neuronal cell structure. Second, whatever the form of the neuron, Cajal
noted that each neuron consisted of a cell body and three other morphologically defined areas.<br></a></p><h2><a name="_Toc3535192" style="color: rgb(55, 71, 79); font-size: 2.143rem; background-color: rgb(255, 255, 255);">Intricate Neuroanatomy: The Neuron</a><br></h2>

<p>The major
cell of the central nervous system is the <b><u>neuron</u></b>. Neurons are
pretty much the most basic unit of the brain, as well as the most complicated
cell in the human body. The brain has about 100 billion neurons with an
estimated 200 trillion connections between them (Buszaki, 2006) or 50 dendrites per neuron. A neuron has a
cell body (also called soma, or perikaryon); dendrites, which are the branched<b>&nbsp; </b>projections of a neuron that act to conduct the electrical
stimulation received from other neural cells to the cell body, or soma, of the
neuron from which the dendrites project. Dendrites extend a short
distance from the soma (each of them having spines that absorb
neurotransmitter); and an axon (also called fiber), which connects one neuron
with others. The fibrous axons occupy more space in the brain than neurons,
dendrites, and spines combined. In short, axons take information away from the cell (longer axons are covered in the myelin sheath, which provides faster transmission.</p>

<p>Neuronal
membranes are specialized for electro-chemical events, the firing of action
potentials and the release/reception of neurostransmitters. This is how neurons
communicate to one another. The dendrites and cell bodies of the neurons
receive information, and the axons transmit the ﬁring pattern of the cell to
the next neuron. Generally, each neuron receives synaptic input from hundreds
or perhaps thousands of other neurons, and its axon distributes this
information via collaterals (branches) to hundreds of other neurons. The
overwhelming majority of neurons are used for the processing of information and
are called interneurons. The more dramatic the level of processing, the more
the interneurons are involved.</p><p><br></p><p style="text-align: center; "><img src="@@PLUGINFILE@@/neuron.png" alt="Neuron" width="432" height="330" class="img-responsive atto_image_button_middle"></p>

<p>Neurons
prefer to take the shortest paths with their surrounding peers. They receive
most of their information from their immediate neighbors and act locally (p.
45). In order to communicate with distant neurons, it requires the use of
costly connections metabolic resources and connections to transporting
electrical pulses over long distances (Buzsaki, 2006).</p><h3><span style="font-size: 1.715rem;"><br></span></h3><h3><span style="font-size: 1.715rem;">Anatomy of a Neuron</span><br></h3><p>Watch this video on the anatomy of a neuron:</p><p><a href="https://www.youtube.com/watch?v=HZh0A-lWSmY">neuron</a><br></p><p></p><p>Communication
between neurons occurs almost exclusively at specialized junctions called <b>&nbsp;<u>synapse</u>s</b>,
using biological molecules called <b><u>neurotransmitters</u></b>. Neurotransmitters
modify ion movements across the neuronal membranes of the synapse and alter
neurotransmission (with each action potential neurotransmitters travel across
the synaptic gap) — neurotransmitters can be excitatory or inhibitory in their
action, or modulate synaptic excitability. The post-synaptic neuron will modify
its ﬁring pattern depending on the summative effect of all the synapses acting
upon it at any moment in time. The action of neurotransmitters depends also on
the speciﬁc receptor type; there is an ever-increasing number of receptor
subtypes allowing for even more complexity of information processing within the
CNS. Drugs are being designed to act on those receptors for therapeutic
purposes.</p>

<p>&nbsp;Here is a short video of the function of the synapse:</p><p><a href="https://www.youtube.com/watch?v=WhowH0kb7n0">synapse</a><br></p><p>And here is a video with a little more info:</p><p><a href="https://www.youtube.com/watch?v=i-XwPjN3ZtI">synapse</a><br></p><p><br></p><h3>Anatomy of an Axon</h3><p><img src="@@PLUGINFILE@@/axon.png" alt="axon" width="670" height="374" class="img-responsive atto_image_button_left"><br></p><p>When
measuring EEG—we are measuring “action potentials” along the axon. An action
potential is a firing—bam!—that is the swapping of potassium and sodium along
the border of the axon. Much of the substance of the brain consists of <b>a<u>xons</u></b>, also called ﬁbers, which
connect one part of the brain with other areas. Low frequency oscillations
(i.e., delta and theta) coordinate long-range communications, between lobes of
the brain (von Stein, Chiang, &amp; Konig, 2000). </p>

<p>This stage of
wiring the brain happens in utero, with the long connections being the most
fundamental (Grubin, 2011). It is these long fibrous white matter tracks that
theta and delta traverse. Many of the axons are myelinated by oligodendrocites
(a type of glial cell), this “insulation,”&nbsp;
serve to increase the speed of axonal conduction; the thicker the <b>myelin sheath</b>, the faster the
conduction. Axons originating from one area (cortex or nucleus) and destined
for another area usually group together and form a tract, also called a pathway
(or fasciculus).</p><p><br></p>

<h3>&nbsp;A Neuron and an Axon</h3><p><img src="@@PLUGINFILE@@/Neuron%20and%20Axon.png" alt="Neuron and Axon" width="679" height="419" class="img-responsive atto_image_button_left"></p><p></p><p></p><p>Moreover,
there are even more numerous glial cells and finely branch blood vessels that
support and nourish the neurons. The neuronal circuits in each subdivision constitute
local networks, which are further integrated to form global neural systems
across subdivisions or divisions. Current neuroscience is based on the belief
that these networks and systems operate through specific mechanisms and play
specific functional roles in the living body.</p>

<p><br></p><p><br></p><p><br></p>

<p>&nbsp;</p><h3><b>What are neurotransmitters and how do they work? </b></h3>

<p>Neurotransmitter substances are biochemical enzymes which,
when released from the presynaptic cell, cross the synaptic cleft and bind with
receptors on the membrane of the post synaptic cell.&nbsp;</p><p>Many neurotransmitter
substances have been identified in the CNS and are divided into two general
classes:&nbsp;</p><p>1. Substances of low molecular weight such as: noradrenaline,
dopamine, serotonin, 5HTP, histamine, glutamate, GABA, glycine&nbsp;</p><p>2. Neuroactive
peptides (which have large molecular weight): i.e. vasopressin, substance P,
somatostatin. </p><p><img src="@@PLUGINFILE@@/neurotransmitters%201.png" alt="Neurotransmitters" width="900" height="545" class="img-responsive atto_image_button_left"><br></p>

<p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><img src="@@PLUGINFILE@@/neurotransmitters%202.png" alt="neurotransmitters 2" width="900" height="772" class="img-responsive atto_image_button_left"><br></p><p><img src="@@PLUGINFILE@@/neurotransmitters%203.png" alt="neurotreanmitters 3" width="900" height="277" class="img-responsive atto_image_button_left"><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p><br></p><p>All transmitter substances meet certain criteria. They must
be able to:</p>

<p><!--[if !supportLists]-->1)&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
<!--[endif]-->be synthesized in the pre-synaptic neuron </p>

<p><!--[if !supportLists]-->2)&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
<!--[endif]-->be stored in vesicles in the pre-synaptic neuron
</p>

<p><!--[if !supportLists]-->3)&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
<!--[endif]-->be released by neuronal activity bind with
receptors on the post synaptic cell </p>

<p><!--[if !supportLists]-->4)&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
<!--[endif]-->be removed from the synaptic cleft </p>

<p>After propagation, the action potential proceeds to the
terminal end of the axon. Depolarization of the terminal membrane causes
changes in voltage gated channels that allow calcium to enter. As Ca+ enters
the cell, synaptic vesicles containing transmitter substance migrate toward the
cell membrane where they fuse with the membrane. The contents of the vesicle then
releases thousands of transmitter molecules into the extracellular synaptic
cleft.</p>

<p>&nbsp;Transmitter molecules
cross the cleft and bind receptors on the post synaptic membrane in a
"lock and key" fashion producing changes which ultimately act to
excite or inhibit the cell. Whether the post synaptic cell moves toward
threshold (excitatory) or away from threshold (inhibitory) is a function of
transmitter action on the receptor of the post synaptic membrane. Some
transmitter substances such as glutamate cause excitatory changes, i.e. they
move the resting membrane potential toward threshold. Such a synaptic potential
is referred to as an excitatory post synaptic potential or EPSP. Other
transmitters such as GABA and dopamine are inhibitory moving the Resting
Membrane Potentials away from threshold and this post synaptic potential is
called an IPSP. However, the action of a specific chemical transmitter
substance on the post synaptic membrane does not depend on the molecular
make-up of the transmitter, but rather on the properties of the receptor with
which the transmitter binds. </p>

More about
neurotransmitters: Acetylcholinestrase (ACh-ase) Once in the synaptic cleft the
transmitter signaling must be turned "off' or stopped. This is carried out
by an enzyme that is present in the synaptic space. In the case of
acetylcholine, this enzyme is called acetylcholinesterase (ACh- ase). ACh -ase
acts to catalyze the acetylcholine and breaks it into acetate and choline which
is reabsorbed into the presynaptic cell for re- synthesis. This series of
events is demonstrated using the transmitter substance acetylcholine as a
model. Many transmitters work in the same way as acetylcholine. However, a
second type of neural transmission may occur in some synapses. This is by way
of so-called second messenger transmission. In second messenger transmission a
transmitter substance binds with a receptor that then causes metabolic activity
inside the cell to produce indirect changes in ionic conductances and thus
voltage changes. Second messenger activation usually lasts longer than that of
chemically gated transmission. Inhibition in neural signaling may also be
produced before the action potential reaches the presynaptic terminal. Specific
to axo-axonic synapses, presynaptic inhibition occurs when the excitatory
action of a presynaptic neuron produces changes in a post synaptic axon to the
extent that it inhibits release of the transmitter.<p></p>

<h2><br></h2><br><p></p><p></p>