6.2.8 Transmission Across a Cholinergic Synapse

• There are over 40 different known neurotransmitters
• One of the key neurotransmitters used throughout the nervous system is acetylcholine (ACh)
• Synapses that use the neurotransmitter ACh are known as cholinergic synapses
• The detailed process of synaptic transmission using ACh is as follows:
  • The arrival of an action potential at the presynaptic membrane causes depolarisation of the membrane
  • This stimulates voltage-gated calcium ion channel proteins to open
  • Calcium ions diffuse down an electrochemical gradient from the tissue fluid surrounding the synapse (high concentration of calcium ions) into the cytoplasm of the presynaptic neurone (low concentration of calcium ions)
  • This stimulates ACh-containing vesicles to fuse with the presynaptic membrane, releasing ACh molecules into the synaptic cleft
  • The ACh molecules diffuse across the synaptic cleft and temporarily bind to ligand-gated sodium ion channels (receptor proteins) in the postsynaptic membrane
  • This causes a conformational change in the receptor proteins, which then open, allowing sodium ions to diffuse down an electrochemical gradient into the cytoplasm of the postsynaptic neurone
  • The sodium ions cause depolarisation of the postsynaptic membrane, re-starting the electrical impulse (that can now continue down the axon of the postsynaptic neurone)
  • To prevent the sodium ion channels staying permanently open and to stop permanent depolarisation of the postsynaptic membrane, the ACh molecules are broken down and recycled
  • The enzyme acetylcholinesterase catalyses the hydrolysis of the ACh molecules into acetate and choline
  • The choline is absorbed back into the presynaptic membrane and reacts with acetyl coenzyme A to form ACh, which is then packaged into presynaptic vesicles ready to be used when another action potential arrives

• This entire sequence of events takes 5 – 10 ms

Synaptic transmission using acetylcholine (ACh)

Unidirectionality

• Synapses ensure the one-way transmission of impulses
• Impulses can only pass in one direction at synapses because neurotransmitter is released on one side and its receptors are on the other – chemical transmission cannot occur in the opposite direction
• This prevents impulses from travelling the wrong way, back to where they were initiated

Summation

• When an impulse arrives at a synapse it does not always cause impulses to be generated in the next neurone
• In some cases, a single impulse that arrives at a synaptic knob is insufficient to generate an action potential in the post-synaptic neurone
  • Only a small amount of acetylcholine is released into the synaptic cleft
  • A small number of the gated ion channels are opened in the axon membrane
  • An insufficient number of sodium ions pass through the membrane
  • The threshold potential is not reached
  • The small amount of acetylcholine attached to receptors is broken down rapidly by acetylcholinesterase

• The effect of multiple impulses can be added together to overcome this in a process known as summation
• There are two types of summation:
  • Temporal
  • Spatial

• There are several benefits of summation
  • It allows for the effect of a stimulus to be magnified
  • A combination of different stimuli can trigger a response
  • It avoids the nervous system being overwhelmed by impulses
    • Synapses act as a barrier and slow down the rate of transmission of a nerve impulse that has to travel along two or more neurones
    • They only allow the impulses to pass on if there has been input from other neurones and receptors

Temporal summation

• If multiple impulses arrive within quick succession the effect of the impulses can be added together to generate an action potential
  • A large amount of acetylcholine is released into the synaptic cleft
  • A large number of the gated ion channels open
  • A sufficient number of sodium ions pass through the membrane

Spatial summation

• Multiple impulses arriving simultaneously at different synaptic knobs stimulating the same cell body can also generate an action potential through spatial summation
• The multiple impulses result in a large amount of acetylcholine being released into the synaptic cleft which results in the generation of an action potential

Temporal summation involves only one synaptic knob whereas spatial summation involves multiple synaptic knobs. The different types of summation produce different shaped graphs.

Inhibition

• Some neurotransmitters result in the generation of an action potential in a postsynaptic neurone
• Other neurotransmitters can prevent the generation of an action potential in a postsynaptic neurone
  • This is inhibition - the impulse stops at the synapse

• One way in which a neurotransmitter can inhibit an impulse is by opening the gated potassium ion channels in the membrane so that potassium ions are able to diffuse out of the cell body
• Each sensory neurone has many branches at the end of its axon that forms synapses with many relay (intermediate) neurones.
• The cell body of each motor neurone is covered with the terminals of many relay neurones
• If the cell body of a motor neurone is subject to both excitatory and inhibitory synapses the following happens:
  • Sodium ions enter the cell body following stimulation by the excitatory synapse
  • The stimulation of the inhibitory synapse causes potassium ions to diffuse out of the cell body
  • This cancels out the effect of the sodium ions entering
  • The threshold potential is not reached so no action potential is generated

The inhibitory synapse (Y) causes the membrane potential to decrease, cancelling out the effect of the excitatory synapse (X) so that the threshold is not reached and no action potential is generated

• Inhibitory synapses play a vital role in the nervous circuit
• They prevent random impulses from being sent around the body
• They allow for specific pathways to be stimulated
  • For example, reflex actions should be rapid but specific
  • If an individual grabs a plank of wood that has a nail sticking out they need their arm muscles to pull their hand away
  • It would be unhelpful if their leg muscles contracted and moved their foot away

• Inhibitory pathways can develop over time
• These pathways are very important for skills such as painting and drawing
  • Children initially struggle with these skills as their inhibitory pathways have not yet developed to refine their uncontrolled movements