2011 Group 1 Project

From CellBiology

Synaptic Junction


Do at end


Charles Sherrington, John Eccles, and the Modern Study of Synaptic Transmission

1897- Term synapse introduced at turn of the century by Charles Sherrington to describe the zone of contact between neurons.

1900- Notion of a receptor introduced by German bacteriologist Paul Ehrlich, he wrote “Chemical Substances are only able to exercise an action on the tissue elements with which they are able to establish a chemical relationship”.

1906- English pharmacologist John Langley postulated sensitivity of skeletal muscle to curare and nicotine was caused by a “receptive molecule.”

1920s- Otto Lowei shows that ACh, a chemical compound, conveys signals from the vagus nerve to the heart

1930s- This discovery led to a debate over how chemical signals could generate electrical activity at other synapses. One side argued that all synaptic transmission is electrical; the action potential in the pre synaptic neuron generates the potential that flows passively into the post synaptic cell. The other that transmission is chemical, initiating the current flow in the post synaptic neuron.

1939- Discovery that action potential in the presynaptic fibre does not lead to direct initiation of action potential in the post synaptic fibre

1950s John Eccles and colleagues experiment on synaptic mechanisms if the spinal motor neuron, giving insight into synapses in the CNS mediated by ionotropic receptors.

1958- Furshpan and Potter first demonstrated electrical synaptic transmission to occur at the giant motor synapse of crayfish. First example of a real electrical synapse.

1963- Krnjevic and Phyllis release a paper titled “Iontophoretic studies of neurons in the cerebral cortex.” This is the first demonstration of glutamate and GABA as neurotransmitters in the CNS

1970s- freeze-fracture techniques applied by Thomas Reese and John Hueser, discovering properties of transmitter release.

1976- First successful recordings of single ACh gated channels by Erwin Neher and Bert Sakmann showing that channels open and close in a step like manner, generating very small rectangular steps of ionic current.

1981- Watkins provides evidence for three different types of ionotropic glutamate receptors

What is a Synaptic Junction

drawing is needed! By definition, synapse is a site between to nerve cells, and junction means; to join. Thus the term synaptic junction describes the region of contact between two neurons where impulses is transmitted from one to another. This communication normally occurs between presynaptic side ( axon terminal of the transmitting neuron ) and postsynaptic side (receiving neuron, muscle or gland). The nerve impulses are conveyed through the action of what is called neurotransmitters including; Acetylcholine (ACh), Norepinephrine (NE), Dopamine (DA), Gamma-aminobutyric acid (GABA). These neurotransmitters are stored and carried by membrane bound organelles called synaptic vesicles. The number of the vesicles varies and depends on whether the synapse is active or not. Moreover, the size is actually dependent upon the neurotransmitter type; fast-acting with 50nm diameter with clear centers, whereas, slow-acting with more than 100nm in diameter with dense core under the electron microscope[references will be added].

The components of a synapse are demonstrated through the schematic sketch. These include;

1) Synaptic bulb axon terminal:

2) Synaptic Vesicle: membrane bound organelles within the presynaptic ending that contains a neurotransmitter substance which is released on depolarization.

3) Neurotransmitter molecules:

4) Synaptic cleft: the gap or small space between the axon terminal and effector cell.

5) Postsynaptic membrane: the portion of effector cell’s membrane.

6) Receptor site:

7) Neurotransmitter binding site:

Types of Synaptic Junctions

Cell to cell communication occurs through a variety of synapses. The most significant synapses are classified under either electrical or chemical synapses. Electrical synapses; or what is known as bridging junctions are defined as electrical and mechanical conductive links that correspond to the narrow gap (gap junction) between the pre and post synaptic neurons of soma (neuron cell bodies). Protein channels are found to be connecting both pre and post synaptic cytoplasmic membranes. As a result, a low resistant electrical pathway is generated between the adjacent neurons, permitting a current flow passively from one neuron to the next. Neurons that are joined this way are referred to as electrically coupled. Moreover, electrical synapses conduct impulses very rapidly due to the short distance gap(3.5nm). Therefore, they are found in regions that depend on fast responses such as reflexes from the brain (jerky movements of the eye). Another key feature of these synapses is the synchronizing activity between the connected neurons. Finally, electrical synapses are usually bidirectional; allows transmission of ions in either direction. Nonetheless, some of these synapses can be unidirectional[references+drawing].

On the contrary, Chemical synapses are known as specialized junctions by which chemical neurotransmitter are released and received. A single chemical synapse has two significant parts; axon terminal and receptive region. The key feature in the first part is membrane bound organelles, referred to as synaptic vesicles. These vesicles store and carry the chemical neurotransmitter molecules. Next, the molecules are secreted by exocytosis from the presynaptic part through the synaptic cleft , which is fluid filled region. The neurotransmitters bind to the receptors located on the postsynaptic membrane. Consequently, postsynaptic channels are opened or closed, resulting in a change in the ions ability to flow in or out of the postsynaptic region. The flow of ions in chemical synapses is merely unidirectional. Furthermore, due to the distance difference between the pre and postsynaptic membranes (20-40nm), transmission of impulses is slower than electrical synapses. Finally, the transmission of signals across these synapses requires the secretion of neurotransmitters and binding to the receptors to generate a synaptic current and membrane potential[references+drawing].

It should be noted that there are other synapses. These include;

Axo-axonic synapse: connects between axon terminal and another.

axodendritic synapse: connects between axon terminal and dendrites

axosomatic synapse: connects between axon terminal and cell body

dendrodendritic synapse: connects between dendrite and another dendrite

Summary of electrical and chemical synapses:

Types of synapses Distance between pre and postsynptic cell membrane intercellular continuity between pre and postsynaptic cells Key features agents of transmission Direction of transmission Location
Electrical 3.5nm Yes Gap junction channels Ion current mostly bidirectional Fast responses regions(brain), i.e. reflexes.
Chemical 20-40nm No Presynaptic vesicles and; synaptic cleft Chemical transmitter(neurotransmitter) Unidirectional. Muscles, glands, neurons.


Synaptic Integration and Modulation

To understand the synaptic junction’s role in neural modulation and integration, it is important to understand why these functions exist. As stated previously, the nervous system contains a network of many interlinking neurons, allowing communication between the brain and spinal cord and the rest of the body. However, the human body does not need all nerve cells to be innervated at one time. It must coordinate the firing of all the nerves so that people can function normally. Included in this is the actions and processing performed subconsciously. For example, we do not focus on contracting our hamstrings then allowing them to be extended while we are walking. Instead, our nervous system allows these movements to occur subconsciously. This coordination occurs through integration and modulation. Modulation occurs at the synaptic junction, where pre synaptic inhibition allows for greater control.

Steps of Transmission on Neural Networks


The interlinking pathways between neurons lead converging and diverging organisations. Convergence describes many neurons synapsing onto a single post synaptic neuron, whereas divergence is when a neuron itself synapses onto multiple neurons. Almost all neurons receive convergent input, which allows for flexible control.

Convergence and Divergence

The Action Potential and Summation

In chemical synaptic junctions, the action potential arriving at the pre synaptic terminal is responsible for the release of neurotransmitters into the synaptic cleft, allowing excitation to continue to the post synaptic cell.

Briefly, the action potential is a rapid depolarization that travels down the axon of a neuron. This is due to several channel types which are voltage dependent. It is an all-or-nothing event, where a certain threshold must be reached before the action potential is produced and fired from the axon hillock. The action potential is always the same size once activated, and travels down collateral branches of the axons as well, to the pre synaptic terminal of many synaptic junctions. This organising allows for greater control of signalling, as each receives many inputs from numerous dendrites called graded potentials. The summation of these graded potentials into the cell must add up to at least the threshold potential to induce an action potential. This table gives the differences between the graded potential and action potential:

Graded Potential Action Potential
Travel a short distance long distance, fast, regenerative
Mostly chemically gated ion channels Require voltage gated ion channels
Strength varies with stimulus Same strength-frequency increases

Graded potentials can vary in size because they depend on the amount of neurotransmitter released. If more neurotransmitters bind to receptors, the amplitude of the depolarization increases. Summation to threshold can occur in two ways, or a combination of these two ways;

Spatial summation: a graded potential can travel to a neuron from several synapses. Spatial summation is the addition of simulation graded potentials arriving from different synapses.

Temporal summation: a second graded potential from a single synapse can occur before a previous one is completed. This means that the second graded potential is added to the potential at which the membrane is in that point in time, not the resting membrane potential. If above threshold, this summation also leads to an action potential.

Pre-synaptic Modulation

Pre Synaptic and Post Synaptic Inhibition

There are two main types of modulation; presynaptic and post synaptic. Postsynaptic modulation occurs through either IPSPs or EPSPs. The axon terminals synapsing onto either the cell body of the post synaptic cell (axosomatic synapse) or its dendrites (axodendratic synapse) are the structures involved in post synaptic inhibition. No modulation of the synapse itself occurs. Instead, these work by either adding to or reducing the combined total of the graded potentials onto the post synaptic cell. Our focus is on the synaptic junction, and since no modulation of the synapse itself, we will shift our attention to presynaptic modulation.

Presynaptic modulation occurs on the presynaptic terminal, directly affecting the release of neurotransmitters onto the target cell. This is known as volume modulation, as the number of neurotransmitters which bind to receptors affects the amplitude of the graded potential to be received by the postsynaptic cell body. Axoaxonic synapses occur in both presynaptic facilitation and inhibition. For the modulatory mechanism to be facilitating, the modulating axon when it is excited causes an increase in the amount of neurotransmitter released from the pre synaptic terminal of the axon it synapses on to. The opposite happens for inhibitory modulation, where excitation of the modulatory neuron causes a decrease in neurotransmitter release from the presynaptic terminal.

This is achieved through the regulation of free calcium inside the cell. Axoaxonic synapses control calcium influx into the presynaptic terminal of its post synaptic cell (that is, the cell which is having its neurotransmitter release modified). By altering the amount of calcium that that flows into a terminal, small changes in the resting membrane potential can make an effective synapse inoperative or a weak synapse highly effective.

Three mechanisms have been recognised as causing pre synaptic inhibition (experimenting with the neurons of invertebrates and mechanoreceptor neurons of vertebrates):

• Activation of metabotropic receptors that leads to simultaneous closure of Ca2+ channels and opening voltage gated K+ channels, both of which decrease the influx of of Ca2+ and enhances repolarization of the cell

• Activation of ionotrpoic GABA-gated Cl- channels, resulting in greater Cl- conductance, decreasing amplitude of action potential in presynaptic terminal. As a result, less depolarzisation occurs and fewerCa2+ channels are activated

• The third is less understood, but seems to work by decreasing sensitivity of one or more steps involved in the release process

Presynaptic facilitation can be caused by an enhance influx of Ca2+. This can be achieved by closing K+ channels, thereby allowing Ca2+ influx to occur for longer. It is thought that facilitation generally occurs by depolarizing the presynaptic terminal, enhancing Ca+ influx in this way.

It is this ability to regulate Ca2+ in the presynaptic terminal that gives chemical synapses their flexible control. Many types of neurotransmitters exist and the ability to manipulate their release is fundemental in prioritizing and organising communication in the nervous system.



As previously mentioned synapse could either be “chemical” or electrical and the presence of neurotransmitters is the distinguishing feature of the chemical synapse. General Neurotransmitters are chemical s produced by the pre-synaptic neuron which is stored in synaptic vesicles and released into the synaptic cleft. The major role for neurotransmitter is to allow transmission of signals between neurons.These neurotransmitters would only bind to specific receptors on the post-synaptic neuron to produce any response. In the synaptic cleft the neurotransmitter could either diffuse and metabolize or undergoes reuptake back into the pre-synaptic neurons. However, special types of neurotransmitters such as Peptide neurotransmitters (histamine, cholecystokinin, neuropeptide Y, and somatostatin) are not produced from terminal buttons of axon but rather from the cell body. Moreover, in rare cases some neurotransmitters such as Nitric oxide and carbon monoxide transport retrograde (from axon back to the soma)which is opposite to the general neurotransmitter where the synaptic vesicles transport is through anterograde.

Neurotransmitters could be categorized into 2 major groups inhibitory and excitatory according to their reaction on the post-synaptic neuron membrane.

Inhibitory neurotransmitters-causes hyperpolarization that prevent action potential in post-synaptic neuron (calm the brain)

Excitatory neurotransmitters-causes depolarization which promotes action potential in post-synaptic neuron(stimulate the brain)

Types of neurotransmitters [2]
Types of Neurotransmitters General Names Function Abnormalities
Biogenic amines [3] Dopamine,epinephrine,noreepinephrine ,serotonin and histamine • Involved in mood and behavior

• Blood pressure control • Sexual behavior

• Arousal

• Motivation

• Fight or Flight response

• Parkinson’s disease

• Mood disorder

• Anxiety

• Schizophrenia

Neuropeptide [4] Neuropeptide Y Influences

• behavior,

• learning

• memory,

• appetite

• sleep cycle

• Anorexia

• Bulimia

• Obesity

Acetylcholine none • Involved in activation of skeletal muscle

• Cognitive function-especially memory

• Myasthenia gravis

• Lambert-Eaton

• Botulism

Excitatory amino neurotransmitters Glutamate,glycine and aspartic acid Major excitatory neurotransmitter in spinal cord • Hyperekplexia (myoclonic startle syndrome)

• Seizures due to ingestion of domoic acid

• Rasmussen's encephalitis

Inhibitory Amino neurotransmitters [5] Gamma Aminobutyric acid (GABA) Major inhibitory neurotransmitter in brain • Stiff person syndrome

• Epilepsy

Gaseous neurotransmitters [6] Nitric oxide and Carbon monoxide • Mediate vasodilatation

• Aids gaseous exchange [7]

• Muscle relaxer

• Regulate gastrointestinal motility

• Ischemia

• gastrointestinal, cardiovascular and neurogical disorder

• erectile dysfunction.

Diseases Associated with Synaptic Junctions Dysfunctions

pictures needed!


Current and Future Research and Developments

( where it's aimed, potential medical applicaitons)

Nany :P and if you guys wanna add in anything else :)


everyone add, good resources that you come across.

(pretty much just thumbnails showing a whole lot of images we've come across. Will help ppl with visualizing)


  • Postsynaptic neuron- neuron after the synapse
  • Presynaptic neuron - neuron before the synapse (usually the one that secrete neurotransmitters)
  • Soma- Cell body of a neuron
  • Synapse- A junction where impulses is transferred from one neuron to the next
  • Terminal buttons- is an area located at the end of the axon responsible for secreting neurotransmitters

--Mark Hill 17:02, 30 March 2011 (EST) OK Group 1, No content has been added to either your discussion or project page. You were meant to have already begun looking into both the topic and references, pasting links on your discussion page. I will see you in the lab tomorrow to discuss whether you are having problems or are simply not doing the work.


  1. <pubmed>21503145</pubmed>
  2. Nicoll Roger A, "Chapter 21. Introduction to the Pharmacology of CNS Drugs" (Chapter). Katzung BG: Basic & Clinical Pharmacology, 11e: http://www.accessmedicine.com.wwwproxy0.library.unsw.edu.au/content.aspx?aID=4519043
  3. Barrett KE, Barman SM, Boitano S, Brooks H, "Chapter 7. Neurotransmitters & Neuromodulators" (Chapter). Barrett KE, Barman SM, Boitano S, Brooks H: Ganong's Review of Medical Physiology, 23e: http://www.accessmedicine.com.wwwproxy0.library.unsw.edu.au/content.aspx?aID=5241648
  4. Schorge JO, Schaffer JI, Halvorson LM, Hoffman BL, Bradshaw KD, Cunningham FG, "Chapter 15. Reproductive Endocrinology" (Chapter). Schorge JO, Schaffer JI, Halvorson LM, Hoffman BL, Bradshaw KD, Cunningham FG: Williams Gynecology: http://www.accessmedicine.com.wwwproxy0.library.unsw.edu.au/content.aspx?aID=3155958
  5. Hauser Stephen L, Beal M. F, "Chapter 360. Mechanisms of Neurologic Diseases" (Chapter). Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison's Principles of Internal Medicine, 17e: http://www.accessmedicine.com.wwwproxy0.library.unsw.edu.au/content.aspx?aID=2900867
  6. <pubmed>9651518</pubmed>
  7. <pubmed>11148674</pubmed>

Coordinator Comment to all Groups

I will add a general comment that will be the same to all groups under this heading.

Referencing Extension Problem

--Mark Hill 13:16, 3 May 2011 (EST) As mentioned in the lecture, I am aware of the referencing extension problem on your project pages. I have the following temporary solution, of removing the extension, so that groups can continue to add content to their project pages. I am also giving everyone a 1 week extension before the peer assessment.

This should only be done if your project page is not allowing you to save changes!

A. The Easy Way....

The following 4 steps can be done on the webpage or select all content in edit mode, copy and paste into a text editor. All steps must be completed before you attempt to save.

  1. In page edit mode, find all <pubmed> reference tags.
  2. Replace this tag with [http://www.ncbi.nlm.nih.gov/pubmed/ Note, there should be no spaces between the internet address and the pmid number.
  3. Now find all </pubmed> reference tags.
  4. Replace this second tag with ]

This will generate a numbered reference list that we can later fix up.

B. The Better Looking Result....

Whatever is between the <ref> </ref></pubmed> tags is what will appear in your reference list, so you can format the reference and link to appear in your reference list.

2011 Projects: Synaptic Junctions | Gap Junctions | Tight Junctions | Desmosomes | Adherens Junctions | Neuromuscular Junction