How do neurons know when to fire?

This is actually an interview style question and a good question to get the candidate to work through themselves from their A level biology knowledge - getting them to practice vocally working things out from their pre-existing knowledge is the basis of Oxbridge interview prep but the general scheme should be as follows:Recognise there is a short answer and a long answer to this question. The short answer is A level biology knowledge that an action potential reaches the axon terminal and this causes the opening of voltage sensitive Ca2+ channels. Ca2+ enters and allows exocytosis of vesicles containing neurotransmitter = 'firing'. The long answer begins earlier, with where does the action potential come from? Well it comes from other neurons, or from receptors such as mechanoreceptors in the skin, or nociceptors in the skin/viscera, or chemoreceptors in the tongue and so on. These involve ion channels sensitive to stimuli other than voltage, and this allows the initiation of the action potential - action potentials do not come from nowhere (apart from perhaps in the heart). Extension work could include:looking at pathologies associated with this chain of events (i.e. draw out the diagram and then every single step has a potential pathology related to it - this is good for students hoping to study Medicine). 'How do neurons know when not to fire?' - so the flipside is how are inhibitory signals integrated in to this system. Once you have established the above chain of events it is pretty simple in that they just oppose the excitatory actions such as by closing Ca2+ channels.