Sybnaptic Transmision

There are up to 100 billion neurons in the human body and an equal or slightly greater number of neuroglia or glial cells, which serve to support and protect the neurons. Each neuron may be connected to up to 10,000 other neurons, passing signals to each other via as many as 1,000 trillion synaptic connections. (Other neurons have very weak connections and this happens when recall to that connection is little which leads less connections to grow to the information.)
Equivalent by some estimates to a computer with a 1 trillion bit per second processor. Estimates of the human brain’s memory capacity vary greatly from 1 to 1,000 terabytes (for comparison, the 19 million volumes in the US Library of Congress represents about 10 terabytes of data).

Information transmission within the brain, such as takes place during the processes of memory encoding and retrieval, is achieved using a combination of chemicals and electricity. It is a very complex process involving a variety of interrelated steps, but a quick overview can be given here.
The core component of the nervous system in general, and the brain in particular, is the neuron or nerve cell, the “brain cells” of popular language. A neuron is an electrically excitable cell that processes and transmits information by electro-chemical signalling. Unlike other cells, neurons never divide, and neither do they die off to be replaced by new ones. By the same token, they usually cannot be replaced after being lost, although there are a few exceptions.
Unlike most body cells, neurons in the brain are only able to divide to make new cells during fetal development and for a few months after birth.
After that, no new brain cells are formed, although existing ones may increase in size until the age of about eighteen years.
They are designed to last a lifetime.
The process by which this information is communicated is called synaptic transmission and can be broken down into four steps. First, the neurotransmitter must be synthesized and stored in vesicles so that when an action potential arrives at the nerve ending, the cell is ready to pass it along to the next neuron. Next, when an action potential does arrive at the terminal, the neurotransmitter must be quickly and efficiently released from the terminal and into the synaptic cleft. The neurotransmitter must then be recognized by selective receptors on the postsynaptic cell so that it can pass along the signal and initiate another action potential. Or, in some cases, the receptors act to block the signals of other neurons also connecting to that postsynaptic neuron. After its recognition by the receptor, the neurotransmitter must be inactivated so that it does not continually occupy the receptor sites of the postsynaptic cell. Inactivation of the neurotransmitter avoids constant stimulation of the postsynaptic cell, while at the same time freeing up the receptor sites so that they can receive additional neurotransmitter molecules, should another action potential arrive.

A typical neuron possesses a soma (the bulbous cell body which contains the cell nucleus), dendrites (long, feathery filaments attached to the cell body in a complex branching “dendritic tree”) and a single axon (a special, extra-long, branched cellular filament, which may be thousands of times the length of the soma).
Every neuron maintains a voltage gradient across its membrane, due to metabolically-driven differences in ions of sodium, potassium, chloride and calcium within the cell, each of which has a different charge. If the voltage changes significantly, an electrochemical pulse called an action potential (ornerve impulse) is generated. This electrical activity can be measured and displayed as a wave form called brain wave or brain rhythm.

Synaptic transmission
Picture from Wikipedia (http://en.wikipedia.org/wiki/Chemical_synapse)
This pulse travels rapidly along the cell's axon, and is transferred across a specialized connection known as a synapse to a neighbouring neuron, which receives it through its feathery dendrites. A synapse is a complex membrane junction or gap (the actual gap, also known as the synaptic cleft, is of the order of 20 nanometres, or 20 millionths of a millimetre) used to transmit signals between cells, and this transfer is therefore known as a synaptic connection. Although axon-dendrite synaptic connections are the norm, other variations (e.g. dendrite-dendrite, axon-axon, dendrite-axon) are also possible.
Each individual neuron can form thousands of links with other neurons in this way, giving a typical brain well over 100 trillion synapses (up to 1,000 trillion, by some estimates). Functionally related neurons connect to each other to formneural networks (also known as neural nets or assemblies). The connections between neurons are not static, though, they change over time. The more signals sent between two neurons, the stronger the connection grows (technically, the amplitude of the post-synaptic neuron’s response increases), and so, with each new experience and each remembered event or fact, the brain slightly re-wires its physical structure.
The interactions of neurons is not merely electrical, though, but electro-chemical. Each axon terminal contains thousands of membrane-bound sacs called vesicles, which in turn contain thousands of neurotransmitter molecules each. Neurotransmitters are chemical messengers which relay, amplify and modulate signals between neurons and other cells. The two most common neurotransmitters in the brain are the amino acids glutamate and GABA; other important neurotransmitters include acetylcholine, dopamine, adrenaline,histamine, serotonin and melatonin.

During childhood, and particularly duringadolescence, a process known as "synaptic pruning" occurs.
Although the brain continues to grow and develop, the overall number of neurons and synapses are reduced by up to 50%, removing unnecessary neuronal structures and allowing them to be replaced by more complex and efficient structures, more suited to the demands of adulthood.

When stimulated by an electrical pulse, neurotransmitters of various types are released, and they cross the cell membrane into the synaptic gap between neurons. These chemicals then bind to chemical receptors in the dendrites of the receiving (post-synaptic) neuron. In the process, they cause changes in the permeability of the cell membrane to specific ions, opening up special gates or channels which let in a flood of charged particles (ions of calcium, sodium, potassium and chloride). This affects the potential charge of the receiving neuron, which then starts up a new electrical signal in the receiving neuron. The whole process takes less than one five-hundredth of a second. In this way, a message within the brain is converted, as it moves from one neuron to another, from an electrical signal to a chemical signal and back again, in an ongoing chain of events which is the basis of all brain activity.
The electro-chemical signal released by a particular neurotransmitter may be such as to encourage to the receiving cell to also fire, or to inhibit or prevent it from firing. Different neurotransmitters tend to act as excitatory (e.g. acetylcholine, glutamate, aspartate, noradrenaline, histamine) or inhibitory (e.g. GABA, glycine, seratonin), while some (e.g. dopamine) may be either. Subtle variations in the mechanisms of neurotransmission allow the brain to respond to the various demands made on it, including the encoding,consolidation, storage and retrieval of memorie


Postsynaptic Stimulation
Once the postsynaptic ion channel is opened, whether directly or indirectly, the effect can be either excitatory (depolarizing) or inhibitory (hyperpolarizing).

Excitatory Postsynaptic Potentials (EPSP)
-Excitatory ion channels are permeable to Na+ and K+
-Because of the electrical and concentration gradient, more Na+
moves into the cell than K+
-The inside of the cell becomes more positive, hence causing a
local depolarization
-If enough depolarization occurs (for example, because the
neurotransmitter released caused nearby ion channels to open),
an action potential is generated
Inhibitory Postsynaptic Potentials (IPSP)

-Inhibitory ion channels are permeable to Cl- and K+

-Because of the concentration gradient (not electrical), Cl- moves
into the cell and K+ moves out of the cell

-The inside of the cell thus becomes more negative, hence causing
local hyperpolarization

-The hyperpolarization will make it more difficult for the cell
membrane potential to reach threshold, thereby making it less
likely that an action potential will be generated


Summation

-Depending on the kind of neurotransmitter released, the effect
can be either excitatory or inhibitory

-The local excitatory depolarizations or inhibitory
hyperpolarizations are graded (passive) potentials and therefore can summate or cause additive changes to the post-synaptic membrane potential. This process is known as summation
*Spatial summation occurs when multiple synapses in nearby
locations are stimulated simultaneously
*Temporal summation occurs when the same channel is
repeatedly opened (for example, because the presynaptic cell
receives many impulses in a row), thereby altering the
membrane potential further before it has the time to return to '
normal

-Although receptor ion channels are all chemically gated, enough
channels to open. An action potential would then be generated

Neurotransmitter Deactivation
If neurotransmitters were continually in the synaptic cleft, the postsynaptic channels would be continually stimulated and the membrane potential would not be able to become stable. There are three ways in which neurotransmitter is deactivated:


1.Degradation: Enzymes located in the synaptic cleft break down
the neurotransmitter into a substance which has no effect on the receptor channel
2.Reuptake: The neurotransmitter can reenter the presynaptic cell through channels in the membrane.
3.Autoreceptors: Receptors for a particular neurotransmitter are located on the presynaptic membrane that act like a thermostat. When there is too much neurotransmitter released in the synapse, it decreases the release of further neurotransmitter when the action potential arrives at the presynaptic membrane. It may accomplish this by decreasing the number of Ca2+ channels that open when the next action potential arrives at the presynaptic terminal


Neurotransmitters
A molecule is considered a neurotransmitter if it meets the following criteria:

-Synthesis of the neurotransmitter occurs in the neuron itself

-It can be found in the presynaptic membrane (because it was carried there from the soma, or because it was synthesized there directly)

-Its release into the synaptic cleft causes a change in the postsynaptic membrane

-Its effect on a neuron is the same whether released exogenously (i.e., from outside the organism as a drug) or endogenously (from the presynaptic terminal)

-Once released, the molecule is specifically removed from the synaptic cleft either by reuse ordegradation


There are two classes of neurotransmitters:

-Small molecules, such as acetylcholine (ACh) or dopamine
*Are packaged in small vesicles
*Are released by exocytosis at active zones associated with Ca2+ channels

-Large molecules made up of chains of amino acids
*Are packaged in large vesicles (which can contain small molecules as well)
*Are released by exocytosis generally anywhere from the presynaptic membrane

Most neurons contain both types of vesicles, but in different concentrations.
Small Molecules

Acetylcholine (ACh)

The only small molecule that is not an amino acid or derived from one
Uses choline as a precursor
Choline cannot be synthesized by the body and must be obtained from external food sources
Used by motor neurons as an excitatory neurotransmitter in the spinal cord
Used at neuromuscular junctions as an excitatory neurotransmitter to influence muscle activation
Used by the Autonomic Nervous System, such as smooth muscles of the heart, as an inhibitory neurotransmitter in preganglionic neurons and postganglionic parasympathetic neurons
Used everywhere in the brain. For example, memory systems of the CNS (may be related to Alzheimer's Disease).
Most receptors for acetylcholine are ionotropic
Monoamines
a. Synthesized from tyrosine
1. Dopamine

Is synthesized in three steps from the amino acid tyrosine
Is the direct precursor to norepinepherine.
Enzyme converts tyrosine to L-DOPA
Generally involved in regulatory motor activity
In the basal ganglia, involved in mood, sensory perception, and attention
Schizophrenics have too much dopamine, patients with Parkinson's Disease have too little
2. Norepinepherine

Synthesized directly from dopamine, and forms the direct precursor to epinepherine. It is synthesized in four steps from tyrosine
Synthesized within vesicles (the only neurotransmitter synthesized this way)
Also known as noradrenaline
Used in the CNS by neurons that project in the cortex, cerebellum, and spinal cord; as such has many uses including sleep/wakefulness regulation
Activates sympathetic and parasympathetic neurons in the Autonomic Nervous System
3. Epinepherine

Synthesized in five steps from tyrosine, and directly from norepinepherine in the biosynthetic pathway
Also known as adrenaline (from Latin: ad means "above" and renal means "kidney," while in Greek,epi means "above" and nephron means "kidney")
Produced by the adrenal medulla, a gland above the kidney
Few neurons in the brain use this neurotransmitter
Activates sympathetic neurons in the Autonomic Nervous System
b. Synthesized from tryptophan
1. Serotonin (5-HT)

Synthesized in two steps from the amino acid tryptophan
Actual name: 5-hydroxytryptamine (5-HT)
Regulates attention and other complex cognitive functions, such as sleep (dreaming), eating, mood, pain regulation
Neurons which use serotonin are distributed throughout the brain and spinal cord
Directly implicated in depression (also norepinepherine)
Used by metabotropic receptors
c. Synthesized from histidine
Histamine

Synthesized from the amino acid histidine
Used in control of smooth muscle, exocrine glands, and vasculature
High concentration in the hypothalamus, which regulates the secretion of horomones
Used during inflammatory reactions
Amino Acids
Glutamate (Glu)

Most prevalent neurotransmitter in the Central Nervous System. Used by more that 50% of neurons
Derived from a -ketoglutarate
Glutamate is the most important excitatory (EPSP) neurotransmitter, exciting about 90% of the postsynaptic terminals to which it contacts
As an excitatory neutrotransmitter, it binds to with ionotropic receptors, causing depolarization by opening Na+ ion channels
At metabotropic receptors, it is modulatory
g-Aminobutyric Acid (GABA)

Synthesized directly from glutamate
GABA is the most important inhibitory (IPSP) neurotransmitter
Present in high concentrations in the CNS, preventing the brain from becoming overexcited
As an inhibitory neutrotransmitter, it binds to both ionotropic and metabotropic receptors, causing hyperpolarization by opening Cl- ion channels
Used by inhibitory interneurons in the spinal cord
Large Molecules
Neuropeptides
Derived from secretory proteins formed in the cell body
They are first processed in the endoplasmic reticulum (ER) and are moved to the Golgi apparatus before being secreted as large vesicles and transported down the axon in preparation for exocytosis
More than 50 peptides have been isolated in nerve cells. For example,
Substance P and enkephalins: Active during inflammation and pain transmission in the PNS
Endorphins: Endogenous opiates which cause euphoria, suppress pain, or regulate responses to stress
Are either excitatory or inhibitory, and can also act as neuromodulators, affecting the amount of neurotransmitter released
Some form part of the neuroendocrine system by functioning both as hormones and neurotransmitters

As neurotransmitters, each one of these molecules undergo a similar life cycle:

Synthesis: Neurotransmitters are synthesized by the enzymatic transformation of precursors. The biosythetic pathway can be immediate (as in GABA from glutamate) or in multiple steps (as in epinepherine from norepinepherine from dopamine, etc.). The synthesis occurs either at the terminal boutons of the axon, or in the soma. In the latter case, it is transported to the axon terminals probably by way of microtubular tracks.
Storage: They are packaged inside synaptic vesicles. These vesicles vary in size, depending on the size of the neurotransmitter.
Release: The neurotransmitters are released from the presynaptic terminal by exocytosis and diffuse across the synaptic cleft to the postsynaptic membrane

Binding: The neurotransmitters bind to receptor proteins imbedded in the postsynaptic cell's membrane. There are two kinds of receptors: ionotropic (direct) and metabotropic (indirect).
Inactivation: The neurotransmitter is degraded either by being broken down enzymatically, or reused by active reuptake in which case the cycle begins again