Mechanisms of communication between neurons

Question 1

Myasthenia Gravis = grave muscle weakness

Answer 1

• Disorder of synaptic transmission
• Symptoms: extreme fatigability

1. fluctuating muscle weakness (proximal (head, neck, trunk) >distal (arms and legs)),
2. problems chewing (dysphagia) and talking (dysarthria) due to weakness of musculature of the jaw and mouth
3. respiratory weakness, in severe cases, can be life threatening if not treated. Hospitalised and placed on an artificial respirator
4. action potentials in nerves are normal as shown by experimental investigations in sufferers. Muscles themselves seem to function properly, as direct electrical stimulation of them leads to normal contractions
5. arises from problem with synpases on muscles

• First described by Thomas Willis in 1672 (first english physician to suggest that the mind resides in the cerebral cortex and not in the hollow venricles)

Question 2

The synapse

Answer 2

• Terminal buttons release a chemical message, called a neurotransmitter, which diffuses across the gap (synaptic cleft) between the presynatic terminal button and the dendrite or cell body of the postsynaptic membrane
• If the neurotransmitter has excitatory effect on the postsynaptic cell, then it will depolarise the postsynaptic neuron and generate an action potential
• This whole process is then repeated for the next neuron in the circuit
• If the neurotransmitter is inhibitory, however, then the postsynaptic cell will become hyperpolarised, and will therefore not fire

Question 3

Structure of a synapse

Answer 3

1. Presynaptic membrane
2. Postsynaptic membrane
3. Dendrite spine
4. Synaptic cleft
5. Synaptic vesicles
6. Microtubules
7. Release zone

Question 4

Types of synapses

Answer 4

• Three types of synapses

1. Axodendritic - the terminal button synapses with a dendrite of a postsynaptic neuron
2. Axosomatic - the terminal button synapses with the cell body (soma) of the postsynaptic neuron
3. Axoaxonic - the terminal button synapses with the axon of the postsynaptic neuron

Question 5

Presynaptic membrane

Answer 5

membrane of the presynaptic terminal button

Question 6

Postsynaptic membrane

Answer 6

membrane of the postsynaptic neuron

Question 7

Dendritic Spine

Answer 7

a ridge on the dendrite of a postsynaptic neuron, with which a terminal button from a presynaptic neuron forms a synapse

Question 8

Synaptic cleft

Answer 8

the tiny gap between the presynaptic and postsynaptic membrane (approx. 20 nanometres wide, a nanometer is a billionth of a metre)

Question 9

Synaptic vesicles

Answer 9

tiny balloons filled with neurotransmitter molecules; found in the release zone of the terminal button

Question 10

Microtubules

Answer 10

long tubes that run down the axon and guide the transport of synaptic vesicles from the soma (cell body) to the axon terminal

Question 11

Release Zone

Answer 11

part of the interior of the presynaptic membrane to which synaptic vesciles fuse in order to release their neurotransmitter into the synaptic cleft

Question 12

Release of a neurotransmitter

Answer 12

• vesicles contain neurotransmitters (NT) molecules
• an action potential in the presynaptic cell triggers vesicles to move towards the cell membrane
• vesicles are guided towards the membrane by proteins
• when an action potential is conducted down an axon (including all of its branches), synaptic vesicles located just inside the terminal buttons begin to move toward the release zone of the cell memrbane
• the vesicles are guided toward the cell membrane of the presynaptic neuron by a group of protein structures
• Guiding proteins act like ropes that help to pull the vesicle and presynaptic membrane together

Question 13

Release of a neuotransmitter - calcium ions

Answer 13

• influx of calcium ions into the presynaptic neuron induces fusion of the two membranes
• neurotransmitter molecules carried by the synaptic vesicles are the released into the synaptic cleft
• this process occurs very rapidly, within just a few milliseconds (thousandth of a second)

Question 14

Activation of receptors on postsynaptic neurons

Answer 14

• Ionotropic receptors have their own binding sites
• When a neurotransmitter molecule attaches to a binding site of the postsynaptic receptors, which are located in the membrane of the postsynaptic cell, an ion channel opens (like a key in a lock)
• The neurotransmitter molecules open neurotransmitter dependent ion channels in the postsynaptic cell
• These channels, once opened, permit the flow of specific ions into and out of the postsynaptic neuron
• Neurotransmittters open ion channels in two different ways, direct and indirect
• The direct method involved receptors that are equipped with their own binding site; these are called ionotropic receptors

Question 15

Movement of ions during postsynaptic potentials

Answer 15

• postsynaptic potentials can be either excitatory (increasing the likelihood that the neuron will depolarise, triggering an action potential) or inhibitory (increasing the likelihood that the neuron will hyperpolarise, and thus not trigger an action potential
• whether a postsynaptic potential is excitatory or inhibitory is determined not by the neurotransmitter that is released into the synapse but the specific ion channel that the neurotransmitter opens

Question 16

Three types of neurotransmitter dependent ion channels that are found in the postsynaptic membrane

Answer 16

1. Sodium
2. Potassium
3. Chloride

• Sodium channels are the most important for triggering excitatory postsynaptic potentials. Sodium-potassium transporters keep sodium outside the cell, waiting for the forces of diffusion and electrostatic pressure to push them in. Once the sodium channels are opened, sodium rushes in and causes depolarisation - this is an excitatory postsynaptic potential (EPSP)
• Due to the slight excess of potassium ions kept inside the cell during rest, when potassium channels open positively, charged potassium ions leave the neuron, thus making the membrane ptetial even more negative and hyperpolarising the cell - this is an inhibitory postsynaptic potential (IPSP)
• The type of postsynaptic receptor determines whether the postsynaptic neuron will be excited (depolarised) or inhibited (hyperpolarised)

Question 17

Neural integration - excitatory postsynaptic potential (EPSP)

Answer 17

• Excitatory postsynaptic potentials (EPSPs) depolarise the postsynaptic cell membrane
• EPSPs increase the likelihood that an action potential will be triggered in the postsynaptic neuron

Question 18

Post synaptic membrane potential before neurotransmitter release

Answer 18

Prior to the release of neurotransmitter molecules from the presynaptic terminal button, the membrane potential of the postsynaptic neuron is at its resting leve (-70mV)

Question 19

Postsynaptic membrane potential after neurotransmitter release

Answer 19

• after neurotransmitter molecules are released from the presynaptic terminal button, they diffuse across the synaptic cleft and bind to receptors on the postsynaptic membrane
• if the neurotransmitter binds to sodium ion channels, these will allow an inflow of sodium ions, causing a depolarisation EPSP in the dendrites of the postsynaptic neuron

Question 20

Neural integration - inhibitory postsynaptic potential (IPSP)

Answer 20

• Inhibitory postsynaptic potentials (IPSPs) hyperpolarise the postsynaptic cell membrane
• IPSPs decrease the likelihood than an action potential will be triggered
• The combined effect of the EPSPs and IPSPs is called neural integration
• The IPSPs tend to cancel out the effects of EPSPs
• The interaction between the effects of EPSPs and IPSPs is known as neural integration
• The rate at which neuron fires is determined by the relative activity of excitatory and inhibitory synapses on its dendrites and cell body
• If the activity of the excitatory synapses increase, the firing rate of the postsynaptic neuron also increases
• Conversely, if the activity of inhibitory synpases increases, the firing rate of the neuron decreases

Question 21

Termination of postsynaptic potentials

Answer 21

• After release of the neurotransmitter and initiation of the postsynaptic potential (either depolarisation or hyperpolarisation), two mechanisms ensure that any excess neurotransmitter substances left in the synaptic cleft are mopped up

1. Reuptake: the neurotransmitter is removed from the synaptic cleft via special transporter molecules in the terminal button. These molecules use energy to draw the neurotransmitter back into the cytoplasm of the presynaptic neuron
2. Enzymatic deactivation - an enzyme in the synaptic cleft destroys the remaining neurotransmitter molecules. Such deactivation seems to occur only for one type of neurotransmitter, called acetylcholine (ACh). The enzyme that destroys ACh is called acetylcholinesterase (AChE); it does its job by breaking ACh into its constituents, acetate and choline

• These two processes ensure that the postsynaptic receptors are only exposed to the neurotransmitter for a very brief period, thereby allowing many depolarisations and hyperpolarisations to occur in a very short space of time

Question 22

Seven steps of the neurotransmitter action at the synapse

Answer 22

1. Neurotransmitters (NT) molecules are synthesised from their precursors from enzymes
2. NT molecules are stored in vesicles
3. NT molecules that leak from vesicles are destroyed by enzymes
4. Action potentials cause vesicles to fuse with the presynaptic membrane, releasing their NT into the synaptic cleft
5. Released NT binds with autoreceptors in the presynaptic membrane, limiting further release of the NT
6. Released NT binds with receptors on postsynaptic membrane, causing ion channels to open
7. Free NT molecules in the synaptic cleft are taken back up by the transporter molecules in the presynaptic membrane, or destroyed by enzymes

Question 23

Classes of neurotransmitters

Answer 23

• There are four classes of small-molecules neurotransmitters: amino acids, monoamines, soluble gases and acetylcholine
• There is one class of large-molecule neurotransmitter: neuropeptides
• Glutamate is the most common excitatory neurotransmitter in the CNS
• GABA (gamma aminobutyric acid) is the most common inhibitory neurotransmitter
• The monamines (dopamine, norepinephrine, serotonin; so named because they are synthesized from a single amino acid) are present in groups of neurons that are located mostly in the brainstem
• Acetylchloline is the neurotransmitter that operates at synapses with muscles, as well as other parts of the CNS

Question 24

Effects of drugs on synaptic functions

Answer 24

• Drugs act upon the CNS in many different ways
• Most drugs that affect behaviour do so by acting on synapses
• Drugs that affect synaptic transmittion are divided into two categories:

1. Agonists - facilitate activity of postsynaptic neurons = increases the activity of the synapse
2. Antagonists - inhibit activity of postsynaptic neurons = decreases the activity of the synapse

• Most drugs influence the activity of the nervous system by modulating the activity of the synapse

Question 25

Agonist Drug Effects

Answer 25

1. Increase the number of NT molecules that are synthesized 2. Increase the number of NT molecules that are stored in vesicles 3. Destroy the enzymes that attack NT molecules 4. Increase the number of vesicles that fuse with the presynaptic cell membrane 5. Decrease the activity of auto receptors 6. Binding directly with the postsynaptic membrane, causing ion channels to open 7. Decreasing the amount of NT that is reuptaken or destroyed by enzymes

Question 26

Antagonist Drug Effect

Answer 26

1. Decrease the number of NT molecules that are synthesized 2. Decrease the number of NT molecules that are stored in vesciles 3. Cause NT to leak from vesicles where they are then attacked by degrading enzymes 4. Decrease the number of vesicles that fuse with the presynaptic cell membrane 5. Increase the activity of autoreceptors 6. Block the ionotropic receptor, preventing the ion channels from opening 7. Increasing the amount of NT that is reuptaken or destroyed by enzymes in the synapse

Question 27

Some specific agonist drug actions

Answer 27

* L-dopa increases the synthesis of dopamine - this drug is used to treat the symptoms of Parkinson's disease * Venom from the black widow spider stimulates the release of acetylcholine (ACh) * Nictotine (e.g. from tobacco) stimulates ACh receptors * Amphetamine, cocaine and methylphenidate block reuptake of dopamine from the synapse. Methlyphenidate (Ritalin) is used to treat attention deficit/hyperactivity disorder in children

Question 28

Some antagonistic drug actions

Answer 28

* PCPA inhibits the synthesis of **serotonin** (important in regulating mood and arousal, and in regulating pain) * **Reserpine** stops the storage of monoamines in vesicles (comes from a plant root, and was discovered many thousands of years ago to have a calming effect. It used to be give to treat high blood pressure, but has since been replaced by drugs with fewer side effects) * **Botulinum toxin** blocks the release of ACh. The toxin is produced by a bacterium that can grow in improperly canned food. It is an extremely potent poison; just one teaspoonful could wipe out the world's entire population. Because ACh works at the synapses with muscles, the effect of the poison is to causes paralysis * **Apomorphine** stimulates dopamine **autoreceptors**, thereby inhibiting the release of dopamine from the presynaptic neuron * **Curare** blocks postsynaptic ACh receptors; as with botulinum toxin, the effect of curare is to cause paralysis. Curare comes from several species of plants found in South America, and it was used to coat the tips of poison arrows and darts. It is extremely fast acting: an animal (or person) hit with a poison tip collapses, stops breathing and dies within minutes. Curare is also used for more human purposes: it is given to paralyse patients who undergo surgery so that their muslces will relax and not contract when they are cut with a scalpel. Of course, an anaesthetic must be given to such patients too, otherwise they would remain fully conscious and able to perceive pain, but would not be able to move

Question 29

Neurotransmitter projection pathways

Answer 29

* Different neurotransmitters are produced by particular clusters of neurons and distributed widely in the CNS * Most of these clusters are in the **brainstem** and **midbrain**

Question 30

Myasthenia Gravis - a disorder of acetylcholine (ACh) receptors

Answer 30

* Autoimmune disorder (like MS) - immune system destroys acetylcholine (ACh) recptors, which are located on synapses with the muscles - this causes weakness * Treated with anticholinesterase (AChE) inhibitors - these increase and prolong the effects of ACh on the postsynaptic membrane * Also treated with immunosuppressive drugs, or by removal of thymus gland * In 1934, Dr Mary Walker noticed that the symptoms of myasthenia gravis were similar to those of people poisoned with curare. The antidote for curare poisoning is a drug called **physostigmine**, which deactivates acetylcholinesterase. By reducing the amount of AChE in the synapse, the amount of ACh in the in the synapse is increased and prolonged. This helps to increase the strength of synaptic transmission at the muscles, and helps to overcome the muscle weakness.