<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>
<p><br></p><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>
<p><a name="_Toc3535192"><br></a></p>
<p><a name="_Toc3535192"><br></a></p>
<p><a name="_Toc3535192"><br></a></p>
<p><a name="_Toc3535192"><br></a></p>
<h2><a name="_Toc3535192" style="color: rgb(55, 71, 79); font-size: 2.143rem; background-color: rgb(255, 255, 255);"><br></a></h2><h2><a name="_Toc3535192" style="color: rgb(55, 71, 79); font-size: 2.143rem; background-color: rgb(255, 255, 255);"><br></a></h2><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><b style="color: rgb(55, 71, 79); font-family: &quot;Open Sans&quot;; font-size: 1.715rem;">What are neurotransmitters and how do they work?</b><br></p>

<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><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><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><span style="font-size: 1rem;"><br></span></p><p><span style="font-size: 1rem;"><br></span></p><p><span style="font-size: 1rem;"><br></span></p><p><span style="font-size: 1rem;"><br></span></p><p><span style="font-size: 1rem;"><br></span></p><p><span style="font-size: 1rem;"><br></span></p><p><span style="font-size: 1rem;">All transmitter substances meet certain criteria. They must be able to:</span><br></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>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>Post Synaptic Potentials</h2>
<p><b>Postsynaptic potentials</b>&nbsp;are changes in the&nbsp;membrane potential&nbsp;of the postsynaptic terminal of a&nbsp;chemical synapse. Postsynaptic potentials are&nbsp;graded potentials, and should not be confused with&nbsp;action potentials&nbsp;although
    their function is to initiate or inhibit action potentials. They are caused by the presynaptic neuron releasing&nbsp;neurotransmitters&nbsp;from the terminal bouton at the end of an&nbsp;axon&nbsp;into the&nbsp;synaptic cleft. The neurotransmitters
    bind to&nbsp;receptors&nbsp;on the postsynaptic terminal.<br></p>
<p>
    </p><p>Neurons have a&nbsp;resting potential&nbsp;of about −70&nbsp;mV. If the opening of the ion channel results in a net gain of positive charge across the membrane, the membrane is said to be&nbsp;depolarized, as the potential comes closer to zero. This
        is an&nbsp;<b>excitatory postsynaptic potential&nbsp;(EPSP)</b>, as it brings the neuron's potential closer to its firing threshold (about −55&nbsp;mV).</p>
    <p>If, on the other hand, the opening of the ion channel results in a net gain of negative charge, this moves the potential further from zero and is referred to as&nbsp;hyperpolarization. This is an&nbsp;<b>inhibitory postsynaptic potential&nbsp;(IPSP)</b>,
        as it changes the charge across the membrane to be further from the firing threshold.</p>
    <p>Neurotransmitters are not inherently excitatory or inhibitory: different receptors for the same neurotransmitter may open different types of ion channels.</p>
    <p>EPSPs and IPSPs are transient changes in the membrane potential, and EPSPs resulting from transmitter release at a single synapse are generally far too small to trigger a spike in the postsynaptic neuron. However, a neuron may receive synaptic inputs
        from hundreds, if not thousands, of other neurons, with varying amounts of simultaneous input, so the combined activity of afferent neurons can cause large fluctuations in membrane potential or&nbsp;subthreshold membrane potential oscillations.
        If the postsynaptic cell is sufficiently depolarized, an&nbsp;action potential&nbsp;will occur.&nbsp;</p>Curious to better understand? This video should help explicate this interesting dynamic.<p></p>
<iframe width="560" height="315" src="https://www.youtube.com/embed/B92rsa1is_k" title="YouTube video player" frameborder="0" allow="accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture" allowfullscreen=""></iframe>
<p><br></p>
<h2>Long Term Potentiation and Long Term Depression</h2>
<p></p>
<p>In&nbsp;neuroscience,&nbsp;<b>long-term potentiation</b>&nbsp;(<b>LTP</b>) is a persistent strengthening of&nbsp;synapses&nbsp;based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal
    transmission between two&nbsp;neurons.<span style="font-size: 10.5px;"> </span>The opposite of LTP is&nbsp;<b>long-term depression (LTD)</b>, which produces a long-lasting decrease in synaptic strength.</p>
<p>Here is a video on long term potentiation</p>
<iframe width="560" height="315" src="https://www.youtube.com/embed/T8e1yH_z-8s" title="YouTube video player" frameborder="0" allow="accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture" allowfullscreen=""></iframe>
<p><br></p>
<p><br></p>
<p>Long term potentiation is one of several phenomena underlying&nbsp;synaptic plasticity, the ability of&nbsp;chemical synapses&nbsp;to change their strength. As memories are thought to be encoded by modification of&nbsp;synaptic strength,&nbsp;LTP is widely
    considered one of the major cellular mechanisms that underlies&nbsp;learning&nbsp;and&nbsp;memory.</p>
<p>LTP was discovered in the rabbit&nbsp;hippocampus&nbsp;by&nbsp;Terje Lømo&nbsp;in 1966 and has remained a popular subject of research since. Many modern LTP studies seek to better understand its basic biology, while others aim to draw a causal link between
    LTP and behavioral learning. Still others try to develop methods, pharmacologic or otherwise, of enhancing LTP to improve learning and memory. LTP is also a subject of&nbsp;clinical research, for example, in the areas of&nbsp;Alzheimer's disease&nbsp;and&nbsp;addiction
    medicine.</p><br>
<p></p>
<p></p>
<p></p>