Brent Cornell

    
Neurotransmitters are chemical messengers released from neurons and function to transmit signals across the synaptic cleft

• Neurotransmitters are released in response to the depolarisation of the axon terminal of a presynaptic neuron
• Neurotransmitters bind to receptors on post-synaptic cells and can either trigger (excitatory) or prevent (inhibitory) a response

Neurotransmitters can trigger a variety of responses depending on the type of cell activated:

    
One example of a neurotransmitter used by both the central nervous system and peripheral nervous system is acetylcholine

• It is commonly released at neuromuscular junctions and binds to receptors on muscle fibres to trigger muscle contraction
• It is also commonly released within the autonomic nervous system to promote parasympathetic responses (‘rest and digest’)

Acetylcholine is created in the axon terminal by combining choline with an acetyl group (derived from mitochondrial Acetyl CoA)

• Acetylcholine is stored in vesicles within the axon terminal until released via exocytosis in response to a nerve impulse

Acetylcholine activates a post-synaptic cell by binding to one of two classes of specific receptor (nicotinic or muscarinic)

• Acetylcholine must be continually removed from the synapse, as overstimulation can lead to fatal convulsions and paralysis

Acetylcholine is broken down into its two component parts by the synaptic enzyme acetylcholinesterase (AChE)

• AChE is either released into the synapse from the presynaptic neuron or embedded on the membrane of the post-synaptic cell
• The liberated choline is returned to the presynaptic neuron where it is coupled with another acetate to reform acetylcholine

Acetylcholine Secretion and Reabsorption

    
Neonicotinoid pesticides are able to irreversibly bind to nicotinic acetylcholine receptors and trigger a sustained response 

• Neonicotinoid pesticides cannot be broken down by acetylcholinesterase, resulting in permanent overstimulation of target cells

While low activation of acetylcholine receptors promotes nerve signalling, overstimulation results in fatal convulsions and paralysis

• Insects have a different composition of acetylcholine receptors which bind to neonicotinoids much more strongly 
• Hence, neonicotinoids are significantly more toxic to insects than mammals, making them a highly effective pesticide

While neonicotinoids have been successfully used to protect crops from pest species, there are disadvantages to their usage 

• Neonicotinoid use has been linked to a reduction in honey bee populations (bees are important pollinators within ecosystems)
• Neonicotinoid use has also been linked to a reduction in bird populations (due to the loss of insects as a food source)
• Consequently, certain countries (including the European Union) have restricted the use of neonicotinoid pesticides

Neonicotinoid Mode of Action