Synapses

Introduction to Synapses

Several neurons are generally needed to transmit a signal from one place in the body to another. So how does the signal pass from one neuron to the next along a neural pathway? The signal must be transmitted across the interface between successive neurons and we will learn how that is accomplished in this next section.

Synapse cells.

Synapse cells. By Miserlou at en.wikipedia (http://upload.wikimedia.org/wikipedia/commons/3/3e/Neurons_big1.jpg)

The term synapse means “coming together.” Where two structures or entities come together, they form a synapse. Although one can use the word synapse to mean any cellular junction, in physiology we traditionally limit its usage to: the junction of two neurons, the junction between a neuron and a target cell (ex. the neuromuscular junction), or the interface between adjacent cardiac muscle cells or adjacent smooth muscle cells. In the nervous system, a synapse is the structure that allows a neuron to pass an electrical or chemical signal to another cell.

Synapse Cells

The cell that delivers the signal to the synapse is the presynaptic cell. The cell that will receive the signal once it crosses the synapse is the postsynaptic cell. Since most neural pathways contain several neurons, a postsynaptic neuron at one synapse may become the presynaptic neuron for another cell downstream.

A presynaptic neuron can form one of three types of synapses with a postsynaptic neuron. The most common type of synapse is an axodendritic synapse, where the axon of the presynaptic neuron synapses with a dendrite of the postsynaptic neuron. If the presynpatic neuron synapses with the soma of the postsynaptic neuron it is called an axosomatic synapse, and if it synapses with the axon of the postsynaptic cell it is an axoaxonic synapse. Although our illustration shows a single synapse, neurons typically have many (even 10,000 or more) synapses.

Synapse Transmission

There are two types of synapses found in your body: electrical and chemical. Electrical synapses allow the direct passage of ions and signaling molecules from cell to cell. In contrast, chemical synapses do not pass the signal directly from the presynaptic cell to the postsynaptic cell. In a chemical synapse, an action potential in the presynaptic neuron leads to the release of a chemical messenger called a neurotransmitter. The neurotransmitter then diffuses across the synapse and binds to receptors on the postsynaptic cell. Binding of the neurotransmitter leads to the production of an electrical signal in the postsynaptic cell.

Why does the body have two types of synapses? Each type of synapse has functional advantages and disadvantages. An electrical synapse passes the signal very quickly, which allows groups of cells to act in unison. A chemical synapse takes much longer to transmit the signal from one cell to the next; however, chemical synapses allow neurons to integrate information from multiple presynaptic neurons, determining whether or not the postsynaptic cell will continue to propagate the signal. Neurons respond differently based on information transmitted by multiple chemical synapses. Let’s take a closer look at the structure and function of each type of synapse.

Electrical synapses transmit action potentials via the direct flow of electrical current at gap junctions. Gap junctions are formed when two adjacent cells have transmembrane pores that align. The membranes of the two cells are linked together and the aligned pores form a passage between the cells. Consequently, several types of molecules and ions are allowed to pass between the cells. Due to the direct flow of ions and molecules from one cell to another, electrical synapses allow bidirectional flow of information between cells. Gap junctions are crucial to the functioning of the cardiac myocytes and smooth muscles.

Structure of an electrical synapse (gap junction), with connections and channels.

Structure of an electrical synapse (gap junction). By (https://commons.wikimedia.org/wiki/File:Gap_cell_junction-en.svg).

Chemical synapses comprise most of the synapses in your body. In a chemical synapse, a synaptic gap or cleft separates the pre- and the postsynaptic cells. An action potential propagated to the axon terminal results in the secretion of chemical messengers, called neurotransmitters, from the axon terminals. The neurotransmitter molecules diffuse across the synaptic cleft and bind to receptor proteins on the cell membrane of the postsynaptic cell. Binding of the neurotransmitter to the receptors on the postsynaptic cell leads to a transient change in the postsynaptic cell’s membrane potential.

Structure of an chemical synapse, with a presynaptic neuron and close-up of the membrane.

Structure of a chemical synapse. (CC BY).

  1. The process of synaptic transmission at a chemical synapse between two neurons follows these steps:
  2. An action potential, propagating along the axon of a presynaptic neuron, arrives at the axon terminal.
  3. The depolarization of the axolemma (the plasma membrane of the axon) at the axon terminal opens Ca2+ channels and Ca2+ diffuses into the axon terminal.
  4. Ca2+ bind with calmodulin, the ubiquitous intracellular calcium receptor, causing the synaptic vesicles to migrate to and fuse with the presynaptic membrane.
  5. The neurotransmitter is released into the synaptic cleft by the process of exocytosis.
  6. The neurotransmitter diffuses across the synaptic cleft and binds with receptors on the postsynaptic membrane.
  7. Binding of the neurotransmitters to the postsynaptic receptors causes a response in the postsynaptic cell.

The response can be of two kinds:

  1. A neurotransmitter may bind to a receptor that is associated with a specific ion-channel which, when opened, allows for diffusion of an ion through the channel. If Na+ channels are opened, Na+ rapidly diffuses into the postsynaptic cell and depolarizes the membrane towards the threshold for an action potential. If K+ channels are opened, K+ diffuses out of the cell, depressing the membrane polarity below its resting potential (hyperpolarization). If Clchannels are opened, Clmoves into the cell leading to hyperpolarization.
  2. The neurotransmitter may bind to a transmembrane receptor protein, causing it to activate a G-protein on the inside surface of the postsynaptic membrane. A cascade of events leads to the appearance of a second messenger (calcium ion, cyclic AMP (cAMP), or IP3) in the cell. Second messengers can have diverse effect on the cell ranging from opening an ion channel to changing cell metabolism to initiating transcription of new proteins.

Neurotransmitter Effects

The response of the postsynaptic cell to a neurotransmitter depends on the specific receptors that are present on its cell membrane. Most neurotransmitters can bind to more than one receptor found in the body and the cell’s response is dependent on which receptor is bound. Different receptors produce different cellular responses because they activate processes in the cell.

Cholinergic Receptors

Cholinergic receptors that open ion channels cause changes in membrane potential.

Cholinergic receptors that open ion channels cause changes in membrane potential. This work by Cenveo is licensed under a Creative Commons Attribution 3.0 United States.

Let’s look at an example. Receptors that can bind the neurotransmitter acetylcholine (ACh) are termed cholinergic receptors – this is the type of receptor. There is more than one cholinergic receptor – the different cholinergic receptors are termed subtypes. One subtype, the nicotinic cholinergic receptor, opens a sodium channel when it binds ACh. Stimulation of a nicotinic cholinergic receptor leads to depolarization of the cell. Another subtype, the muscarinic cholinergic receptor, opens a potassium channel when it binds ACh. Stimulation of a muscarinic cholinergic receptor leads to cell hyperpolarization. Acetylcholine can either excite or inhibit the postsynaptic cell depending on whether that cell has the nicotinic or muscarinic receptor subtype.

In the example we just considered, both receptor subtypes were linked to distinct ion channels. It is also possible for one receptor subtype to be linked to an ion channel while another subtype leads to the production of a second messenger. In this case, the timing of the postsynaptic cell’s response is different. Opening an ion channel takes very little time compared to the complex signaling that occurs with a second messenger. The response is fast with a receptor linked to an ion channel and is slow with a receptor that leads to a second messenger cascade. Although slower, second messenger cascades can produce more diverse cellular effects and have the advantage of amplification. Binding of a single molecule of neurotransmitter can produce many molecules of the second messenger. In contrast, if the receptor opens an ion channel, a single molecule of neurotransmitter (or sometimes two molecules) is needed to open a single ion channel in the postsynaptic cell.

A receptor that produces a second messenger in the postsynaptic cell. Second messengers can lead to a wide range of effects in the postsynaptic cell.

A receptor that produces a second messenger in the postsynaptic cell. Second messengers can lead to a wide range of effects in the postsynaptic cell. This work by Cenveo is licensed under a Creative Commons Attribution 3.0 United States. 

Synaptic Potentials

An excitatory postsynaptic potential depolarizes the membrane bringing it closer to the threshold potential.

An excitatory postsynaptic potential depolarizes the membrane bringing it closer to the threshold potential. This work by Cenveo is licensed under a Creative Commons Attribution 3.0 United States.

Postsynaptic potentials develop in the postsynaptic cell’s membrane when neurotransmitter binding to receptors leads to the opening of ion channels. An excitatory postsynaptic potential (EPSP) occurs if the membrane is depolarized by the ion movement. If, on the other hand, the membrane becomes hyperpolarized when the ions move, an inhibitory postsynaptic potential (IPSP) is generated. EPSPs and IPSPs are local potentials.

EPSP

Opening of sodium- or calcium channels leads to depolarization of the membrane. If there is sufficient depolarization, the threshold potential is reached and an action potential will be produced in the postsynaptic membrane. Since an EPSP depolarizes the membrane, it facilitates action potentials.

IPSP

An inhibitory postsynaptic potential hyperpolarizes the membrane taking it farther from the threshold potential.

An inhibitory postsynaptic potential hyperpolarizes the membrane taking it farther from the threshold potential. This work by Cenveo is licensed under a Creative Commons Attribution 3.0 United States. 

Opening of potassium- or chloride channels leads to hyperpolarization of the membrane. (Since the current is outward for potassium ions, and inward for chloride ions, opening of either of these two channels will cause the postsynaptic membrane to hyperpolarize.) A hyperpolarized membrane has moved farther from the threshold potential and has less probability of producing an action potential. Since an IPSP hyperpolarizes the membrane, it inhibits action potentials.

Remember that a neuron synapses with many other neurons. So a postsynaptic neuron can receive signals from many presynaptic neurons simultaneously. Whether or not the postsynaptic cell has an action potential depends on the summation (the additive effect) of all the incoming signals. Each active synapse can result in a local potential (either an EPSP or an IPSP). The net effect of all the local potentials on the trigger zone determines whether or not there is an action potential in the postsynaptic cell.

There are two different ways that local potentials can sum to excite the postsynaptic cell to have an action potential. Temporal summation occurs when successive EPSPs at a single synapse occur in rapid succession. The successive potentials occur before the previous ones die out producing an increasing membrane depolarization.

Temporal summation occurs when one synapse stimulates the postsynaptic cell very quickly and the EPSPs produced in the postsynaptic cell piggyback on each other causing an increasing level of depolarization.

Temporal summation occurs when one synapse stimulates the postsynaptic cell very quickly and the EPSPs produced in the postsynaptic cell piggyback on each other causing an increasing level of depolarization. This work by Cenveo is licensed under a Creative Commons Attribution 3.0 United States.

The effect of temporal summation on membrane voltage at the trigger zone. The threshold voltage is attained and the postsynaptic cell fires an action potential.

The effect of temporal summation on membrane voltage at the trigger zone. The threshold voltage is attained and the postsynaptic cell fires an action potential. This work by Cenveo is licensed under a Creative Commons Attribution 3.0 United States.

Summation can also occur when multiple presynaptic neurons stimulate the postsynaptic neuron at the same time (spatial summation). Each individual synapse lets in a limited number of ions and alters the membrane potential a little. The collective effect of all the synapses allows in enough ions to reach the threshold potential and an action potential is triggered.

Spatial summation occurs when the collective effect of multiple synapses depolarizes the postsynaptic neuron to threshold resulting in an action potential.

Spatial summation occurs when the collective effect of multiple synapses depolarizes the postsynaptic neuron to threshold resulting in an action potential. This work by Cenveo is licensed under a Creative Commons Attribution 3.0 United States.

The interplay between IPSPs and EPSPs is important. Whether an action potential is going to be produced depends not just on the summation of the EPSPs, but on the summation of EPSPs and IPSPs. The algebraic sum of all EPSPs and IPSPs has to be of sufficient amplitude to raise the membrane potential to the threshold for an action potential. What this means is that if the IPSPs prevail, then the post-synaptic cell will be “silent.” One can, therefore, visualize the process of summation as a “tug-of-war” between excitatory and inhibitory currents induced by the binding of neurotransmitters on excitatory or inhibitory postsynaptic receptors, respectively.

Neurotransmitters Classes

Neurotransmitters are organic molecules that allow neurons to communicate with each other and with target cells. Neurotransmitters fall into four classes based on their chemical makeup.

Acetylcholine (ACh) is a small molecule formed from acetate and choline. It is in a class by itself. Acetylcholine is the sole neurotransmitter used at the neuromuscular junction and is also the neurotransmitters used by the parasympathetic nervous system.

The molecular structure of acetylcholine, pointing out the choline and acetyl groups of the molecule.

The structure of acetylcholine.

Some amino acids act as neurotransmitters. Glycine and γ-aminobutyric acid (GABA) are the most common inhibitory neurotransmitters in the spinal cord and brain, respectively. Glutamate (glutamic acid) and aspartate are excitatory neurotransmitters found in the brain and spinal cord, respectively.

Biogenic amines (monoamines) are formed from amino acids from which the carboxyl terminus is removed. Three of the biogenic amines, called the catecholamines, are grouped together as they are all derived from the same amino acid, L-tyrosine. The catecholamines include: norepinephrine (noradrenalin), epinephrine (adrenalin) and dopamine (dopamine can also be made from phenylalanine). Norepinephrine (NE) is the neurotransmitter of the sympathetic nervous system (your fight or flight response). Epinephrine (E) has similar effects to NE, but is less abundant. Dopamine is best known for its role in motor inhibition. Loss of dopamine producing neurons in Parkinson disease leads to dyskinesias (movement disorders). Catecholamines bind to adrenergic receptors. Other biogenic amines include serotonin and histamine.

The molecular structures of various amino acid and biogenic amine neurotransmitters - Epinephrine, Norepinephrine, Dopamine, Serotonin, Histamine.

The structures of the biogenic amine neurotransmitters. This work by Cenveo is licensed under a Creative Commons Attribution 3.0 United.

Neuropeptides are small proteins that function as neurotransmitters. They are the largest neurotransmitters and can range from just a couple of amino acids to as many as 40. An example of neuropeptide neurotransmitters is β-endorphin, the chemical associated with the elevated mood experienced with exercise.

Molecular examples of neuropeptide neurotransmitters - Enkephalin, Substance P, Cholecystokinin, B-endorphin.

Examples of neuropeptide neurotransmitters. This work by Cenveo is licensed under a Creative Commons Attribution 3.0 United States.