Separate or continuous?
In the late 19th century Camillo Golgi held that the nervous system was one continuous net, but from about 1888 Santiago Ramón y Cajal, using Golgi's own silver stain on bird brains, argued for the "neuron doctrine": each neuron is a separate cell that merely touches others. The two shared the 1906 Nobel Prize yet contradicted each other in their lectures. In 1897 the British physiologist Charles Sherrington named the contact point a "synapse", from the Greek for "to clasp together", and in The Integrative Action of the Nervous System (1906) showed that reflexes are shaped by synaptic excitation and inhibition. In the 1950s electron microscopes revealed a cleft about 20 nanometres wide, confirming Cajal.
Electrical or chemical?
In 1921 Otto Loewi, acting on an experiment he said came to him in a dream, showed that fluid from a frog heart whose vagus nerve had been stimulated slowed a second heart. That "vagus substance" was acetylcholine — the first evidence that signals cross synapses chemically. John Eccles initially championed electrical transmission but accepted chemical transmission after his own experiments. In 1952 Bernard Katz and Paul Fatt found that neurotransmitter is released in fixed packets, or quanta, later explained by tiny synaptic vesicles. When an electrical impulse reaches the axon terminal, calcium flows in, vesicles fuse with the membrane and transmitter spills into the cleft to bind receptors on the next cell. Thomas Südhof won a 2013 Nobel Prize for revealing the molecular machinery that does this within a millisecond. Key transmitters include dopamine, serotonin, glutamate and GABA, and electrical synapses, where ions pass directly, exist too, for example in heart muscle.
Learning, memory and pruning
In 1949 Donald Hebb proposed that learning is a change in synaptic strength — often summarised as "neurons that fire together wire together". In 1973 Tim Bliss and Terje Lømo supported this by finding long-term potentiation: brief high-frequency stimulation of the rabbit hippocampus strengthened synaptic transmission for hours or more. Synapses strengthening or weakening with use is central to neuroplasticity. Infant brains overproduce synapses and then prune less-used ones through adolescence. A 2016 study suggested that variants of the immune gene C4 may be linked to excessive pruning and schizophrenia risk, though causation is not established. Many antidepressants and anaesthetics, as well as nicotine and caffeine, act at synapses.
FAQ
- Do synapses only decline with age?
- Synapses form and disappear throughout life. Some loss can occur with ageing, but learning, exercise and social activity are thought to help build new connections.
- How does synaptic transmission differ from hormones?
- Synaptic transmission is short-range, crossing tens of nanometres in milliseconds; hormones are slower, broadcast signals carried in the blood throughout the body.
Sources reviewed: 2026-10-26
References
- Ramón y Cajal, S. (1888). Estructura de los centros nerviosos de las aves. Revista Trimestral de Histología Normal y Patológica, 1, 1–10.
- Sherrington, C. S. (1906). The Integrative Action of the Nervous System. New Haven: Yale University Press.
- Loewi, O. (1921). Über humorale Übertragbarkeit der Herznervenwirkung. Pflügers Archiv für die gesamte Physiologie, 189, 239–242.
- Hebb, D. O. (1949). The Organization of Behavior: A Neuropsychological Theory. New York: Wiley.
- Fatt, P., & Katz, B. (1952). Spontaneous subthreshold activity at motor nerve endings. Journal of Physiology, 117(1), 109–128.
- De Robertis, E. D. P., & Bennett, H. S. (1955). Some features of the submicroscopic morphology of synapses in frog and earthworm. Journal of Biophysical and Biochemical Cytology, 1(1), 47–58.
- Eccles, J. C. (1957). The Physiology of Nerve Cells. Baltimore: Johns Hopkins Press.
- Bliss, T. V. P., & Lømo, T. (1973). Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. Journal of Physiology, 232(2), 331–356.
- Südhof, T. C. (2013). Neurotransmitter release: The last millisecond in the life of a synaptic vesicle. Neuron, 80(3), 675–690.
- Sekar, A., et al. (2016). Schizophrenia risk from complex variation of complement component 4. Nature, 530(7589), 177–183.