Across the Gap: Synaptic Transmission

"You are your synapses. They are who you are." Joseph LeDoux, 2002 (in Synaptic Self)

Communication of information between neurons is accomplished by movement of chemicals across a small gap called the synaptic cleft. When the Action Potential reaches the axon terminal,chemicals, called neurotransmitters, are released from the neuron at the presynaptic nerve terminal. (Axon) The neurotransmitters then cross the synaptic cleft and are accepted by the post-synaptic neuron at specialized sites called receptors. (Dendrite)

The action that follows activation of a receptor site may be either depolarization (an excitatory postsynaptic potential) or hyperpolarization (an inhibitory postsynaptic potential). A depolarization makes it MORE likely that an action potential will fire; a hyperpolarization makes it LESS likely that an action potential will fire.

Synaptic Transmission Neurotransmitters: are chemicals produced by the neuron and packaged into vesicles at axon terminals. At rest, neurotransmitter-containing vesicles are stored at the axon terminals of the neuron

A small number of vesicles are positioned along the pre-synaptic membrane in places called "active zones.“ Other vesicles are held close to these zones, but further from the membrane itself until they are needed. The vesicles are held in place by Ca 2+- sensitive vesicle membrane proteins (VAMPs), which bind to actin filaments, microtubules, and other elements of the cytoskeleton.

–When an action potential reaches the axon terminal of a neuron, voltage-dependent calcium (Ca 2+ ) channels embedded in the pre- synaptic membrane open and Ca 2+ rushes in. – The Ca 2+ ions bind to the vesicles and cause the vesicles to move toward the membrane.

Fusion then takes place: the vesicle membrane and the pre-synaptic membrane connect to form a small pore. This pore grows larger and larger until the vesicle releases its contents into the synaptic cleft (exocytosis). Following exocytosis, the vesicular membrane forms a pit and pinches off to form a new vacant vesicle. This vesicle is then either refilled with more of the neurotransmitter, or sent to the cell body where it is processed into a new vesicle.

The neurotransmitters diffuse across the synaptic cleft and bind to receptors on the post-synaptic membrane. This causes ionic channels to open. Some neurotransmitters cause Na+ channels to open, allowing the influx of Na+ ions into the neuron and generating a new action potential.These are excitory neurotransmitters.

Some neurotransmitters open Cl - channels. This allows the influx of Cl - ions into the neuron and make the inside even more negative. In this case, an action potential will NOT be produced. Neurotransmitters that act in this way are said to be inhibitory.

After a neurotransmitter molecule has been recognized by a post-synaptic receptor, it is released back into the synaptic cleft. It must be quickly removed or chemically inactivated in order to prevent constant stimulation of the post-synaptic cell and an excessive firing of action potentials.

Some neurotransmitters are removed from the synaptic cleft by special transporter proteins on the pre-synaptic membrane. These transporter proteins carry the neurotransmitter back into the pre-synaptic cell, where it is either re-packaged into a vesicle or broken down by enzymes. This is called reuptake.

Other neurotransmitters merely quickly diffuse away from the receptors into the surrounding medium. One important neurotransmitter, acetylcholine, has a specialized enzyme for inactivation right in the synaptic cleft. Acetylcholinesterase is an enzyme which serves to inactivate acetylcholine by hydrolysis.

SUMMATION: One neuron can have thousands of synapses on its body and dendrons. So it has many inputs, but only one output. The output through the axon is called the Grand Postsynaptic Potential (GPP) The GPP is the sum of all the excitatory and inhibitory potentials from all that cell’s synapses.

If there are more excitatory potentials than inhibitory ones then there will be a GPP, and the neuron will “fire”, but if there are more inhibitory potentials than excitatory ones then there will not be a GPP and the neuron will not fire.

This summation is the basis of the processing power in the nervous system. A nervous system,including a human brain, is made by connecting enough neurons together

WHY THE GAPS? 1. They make sure that the flow of impulses is in one direction only. This is because the vesicles containing the transmitter are only in the presynaptic membrane and the receptor molecules are only on the postsynaptic membrane.

2. They allow integration. An impulse traveling down a neuron may reach a synapse which has several post synaptic neurons, all going to different locations. The impulse can thus be dispersed. This can also work in reverse, where several impulses can converge at a synapse. 3. They allow ‘summation’ to occur. Summation allows for ‘grading’ of nervous response – if the stimulation affects too few presynaptic neurons or the frequency of stimulation is too low, the impulse is not transmitted across the cleft.

4. They allow the ‘filtering out’ of continual unnecessary or unimportant background stimuli. If a neuron is constantly stimulated (e.g. clothes touching the skin) the synapse will not be able to renew its supply of transmitter fast enough to continue passing the impulse across the cleft. This ‘fatigue’ places an upper limit on the frequency of depolarization.

Neurotransmitters –Chemicals that are produced within a neuron, are released by a stimulated neuron, and cause an effect on adjoining neurons. –There are two types of neurotransmitters: 1. Small molecule neurotransmitters: 2. Neuropeptides

1.Small molecule neurotransmitters : -synthesized locally within the axon terminal, usually by enzyme action. -They are released in a pulse into synaptic cleft every time an action potential reaches an axon terminal. Their effect is point-to- point and short in duration.

2.Neuropeptides : -synthesized by transcription and translation of gene sequence. ER and Golgi Apparatus are involved in packaging. -are released gradually in response to general increases in neuron firing; -their effects are usually widespread because they are often released into extracellular fluid or the bloodstream

it was initially assumed that there is only one kind of receptor for each neurotransmitter; research has shown that each neurotransmitter binds to more than one type of receptor receptor subtypes are located in different brain areas this allows the same neurotransmitter to signal differently at various locations; postsynaptic neurons are influenced in different ways based on the type of receptor

Acetylcholine Acetylcholine (Ach) is an example of a small molecule neurotransmitter. It is an excitatory neurotransmitter The synthesis of ACh requires the enzyme choline acetyltransferase It is found at various locations throughout the central and peripheral nervous systems and at all neuromuscular junctions.

Dopamine Dopamine & epinephrine are primarily inhibitory neurotransmitters that produce arousal. the most likely explanation for this effect is that the postsynaptic cells for these neurotransmitters are themselves inhibitory. There are 3-4 times more cells that respond to dopamine in the CNS than cells that respond to epinephrine. Dopamine affects a wide variety of brain processes, many of which are involved in the control of movement, the formation of emotional responses, and the perception of pain and pleasure.

Too little dopamine is associated with Parkinson’s disease. Too much dopamine is associated with schizophrenia Dopamine is also associated with addiction to cocaine, alcohol, and other drugs It may also play an important role in obesity. According to a study, obese people have fewer receptors for dopamine.

Serotonin Within the brain, serotonin is associated with a variety of important centers, including those that control appetite, memory, sleep, and learning. Serotonin is also closely associated with feelings of well being, acting in conjunction with endorphins, GABA, and dopamine to generate the biological process known as the reward cascade. Many pharmaceuticals designed to fight depression, bipolar disorder, and a number of other mood-related conditions function by stimulating serotonin production or inhibiting its uptake.

GABA GABA or gamma-aminobutyric acid is the most important and widespread inhibitory neurotransmitter in the brain. Excitation in the brain must be balanced with inhibition. Too much excitation can lead to restlessness, irritability, insomnia, and even seizures. GABA is able to induce relaxation, analgesia, and sleep. Barbiturates are known to stimulate GABA receptors, and hence induce relaxation. Several neurological disorders, such as epilepsy, sleep disorders, and Parkinson’s disease are affected by this neurotransmitter.

Endorphins endorphins ("endogenous morphine") are one of several morphine-like substances (opioids) that occur within our brains. Their molecular structure is very similar to morphine but with different chemical properties. Endorphins are polypeptides containing 30 amino acid units. They are manufactured by the body to reduce stress and relieve pain. Usually produced during periods of extreme stress, endorphins naturally block pain signals produced by the nervous system.

The human body produces at least 20 different endorphins Beta- endorphin appears to be the endorphin that seems to have the strongest affect on the brain and body during exercise. Prolonged, continuous exercise like running, long-distance swimming, aerobics, cycling or cross-country skiing appears to contribute to an increased production and release of endorphins. This results in a sense of euphoria that has been popularly labeled the "runner's high."

endorphins are believed to produce four key effects on the body/mind: –they enhance the immune system, –they relieve pain, –they reduce stress, –they postpone the aging process. –Scientists also have found that beta-endorphins can activate human NK (Natural Killer) cells and boost the immune system against diseases and kill cancer cells.

Chocolate is by far the most popular endorphin-producing food on Earth. In addition to sugar, caffeine and fat, chocolate contains more than 300 different constituent compounds, including anandamide, a chemical that mimics marijuana's soothing effects on the brain. It also contains chemical compounds such as flavanoids (which are also found in wine) that have antioxident properties and reduce serum cholesterol. Although the combined psychochemical effects of these compounds on the central nervous system are poorly understood, the production of endorphins are believed to contribute to the renowned "inner glow" experienced by dedicated chocolate lovers.