system. integration of synaptic inputs main article: summation (neurophysiology) in general, if an excitatory synapse is strong enough, an action potential in the presynaptic neuron will trigger an action potential in the postsynaptic cell. in many cases the excitatory postsynaptic potential (epsp) will not reach the threshold for eliciting an action potential. when action potentials from multiple presynaptic neurons fire simultaneously, or if a single presynaptic neuron fires at a high enough frequency, the epsps can overlap and summate. if enough epsps overlap, the summated epsp can reach the threshold for initiating an action potential. this process is known as summation, and can serve as a high pass filter for neurons. on the other hand, a presynaptic neuron releasing an inhibitory neurotransmitter, such as gaba, can cause an inhibitory postsynaptic potential (ipsp) in the postsynaptic neuron, bringing the membrane potential farther away from the threshold, decreasing its excitability and making it more difficult for the neuron to initiate an action potential. if an ipsp overlaps with an epsp, the ipsp can in many cases prevent the neuron from firing an action potential. in this way, the output of a neuron may depend on the input of many different neurons, each of which may have a different degree of influence, depending on the strength and type of synapse with that neuron. john carew eccles performed some of the important early experiments on synaptic integration, for which he received the nobel prize for physiology or medicine in 1963. volume transmission when a neurotransmitter is released at a synapse, it reaches its highest concentration inside the narrow space of the synaptic cleft, but some of it is certain to diffuse away before being reabsorbed or broken down. if it diffuses away, it has the potential to activate receptors that are located either at other synapses or on the membrane away from any synapse. the extrasynaptic activity of a neurotransmitter is known as volume transmission. it is well established that such effects occur to some degree, but their functional importance has long been a matter of controversy. recent work indicates that volume transmission may be the predominant mode of interaction for some special types of neurons. in the mammalian cerebral cortex, a class of neurons called neurogliaform cells can inhibit other nearby cortical neurons by releasing the neurotransmitter gaba into the extracellular space. along the same vein, gaba released from neurogliaform cells into the extracellular space also acts on surrounding astrocytes, assigning a role for volume transmission in the control of ionic and neurotransmitter homeostasis. approximately 78% of neurogliaform cell boutons do not form classical synapses. this may be the first definitive example of neurons communicating chemically where classical synapses are not present. relationship to electrical synapses an electrical synapse is an electrically conductive link between two abutting neurons that is formed at a narrow gap between the pre- and postsynaptic cells, known as a gap junction. at gap junctions, cells approach within about 3.5 nm of each other, rather than the 20 to 40 nm distance that separates cells at chemical synapses. as opposed to chemical synapses, the postsynaptic potential in electrical synapses is not caused by the opening of ion channels by chemical transmitters, but rather by direct electrical coupling between both neurons. electrical synapses are faster than chemical synapses. electrical synapses are found throughout the nervous system, including in the retina, the reticular nucleus of the thalamus, the neocortex, and in the hippocampus. while chemical synapses are found between both excitatory and inhibitory neurons, electrical synapses are most commonly found between smaller local inhibitory neurons. electrical synapses can exist between two axons, two dendrites, or between an axon and a dendrite. in some fish and amphibians, electrical synapses can be found within the same terminal of a chemical synapse, as in mauthner cells. effects of drugs main article: neuropharmacology one of the most important features of chemical synapses is that they are the site of action for the majority of psychoactive drugs. synapses are affected by drugs, such as curare, strychnine, cocaine, morphine, alcohol, lsd, and countless others. these drugs have different effects on synaptic function, and often are restricted to synapses that use a specific neurotransmitter. for example, curare is a poison that stops acetylcholine from depolarizing the postsynaptic membrane, causing paralysis. strychnine blocks the inhibitory effects of the neurotransmitter glycine, which causes the body to pick up and react to weaker and previously ignored stimuli, resulting in uncontrollable muscle spasms. morphine acts on synapses that use endorphin neurotransmitters, and alcohol increases the inhibitory effects of the neurotransmitter gaba. lsd interferes with synapses that use the neurotransmitter serotonin. cocaine blocks reuptake of dopamine and therefore increases its effects. history and etymology during the 1950s, bernard katz and paul fatt observed spontaneous miniature synaptic currents at the frog neuromuscular junction. based on these observations, they developed the 'quantal hypothesis' that is the basis for our current understanding of neurotransmitter release as exocytosis and for which katz received the nobel prize in physiology or medicine in 1970. in the late 1960s, ricardo miledi and katz advanced the hypothesis that depolarization-induced influx of calcium ions triggers exocytosis. sir charles scott sherringtonin coined the word 'synapse' and the history of the word was given by sherrington in a letter he wrote to john fulton: 'i felt the need of some name to call the junction between nerve-cell and nerve-cell... i suggested using "syndesm"... he consulted his trinity friend verrall, the euripidean scholar, about it, and verrall suggested "synapse" (from the greek "clasp").'–charles scott sherrington