Background
The nervous system first began to be encompassed within the scope of general physiological studies in the late 1800s, when Charles Sherrington began to test the electrical properties of neurons. His main contributions to neurophysiology involved the study of the knee-jerk reflex and the inferences he made between the two reciprocal forces of excitation and inhibition. He postulated that the site of this modulatory response occurs at the intercellular space of a unidirectional pathway of neural circuits. He first introduced the possible role of evolution and neural inhibition with his suggestion that “higher centers of the brain inhibit the excitatory functions of the lower centers”.
Much of today's knowledge of chemical synaptic transmission was gleaned from experiments analyzing the effects of acetylcholine release at neuromuscular junctions, also called end plates. The use of squid axon was pioneered by Bernard Katz and Alan Hodgkin pioneered the use of the giant squid axon as an experimental model for the study of the nervous system. The relatively large size of the neurons allowed the use of finely-tipped electrodes to monitor the electrophysiological changes that fluctuate across the membrane. In 1941 Katz' implementation of microelectrodes in the gastrocnemius sciatic nerve of frogs’ legs illuminated the field. It soon became generalized that the end-plate potential (EPP) alone is what triggers the muscle action potential, which was manifested through contractions of the frog legs.
One of Katz's seminal findings, in studies carried out with Paul Fatt in 1951, was that spontaneous changes in muscle cell membrane potential occur even without the stimulation of the presynaptic motor neuron. These spikes in potential are similar to action potentials except that they are much smaller typically less than 1 mV, and were thus called miniature end plate potentials (MEPPs). In 1954, the introduction of the first electron microscopic images of postsynaptic terminals revealed that these MEPPs were created by synaptic vesicles carrying neurotransmitters. This sporadic release of quantal amounts of neurotransmitter leads to the vesicle hypothesis by Katz and del Castillo, which attributes quantization of transmitter release to its association with synaptic vesicles. This indicated to Katz that action potential generation can be triggered by the summation of these individual units, each equivalent to an MEPP.
Read more about this topic: Summation (neurophysiology)
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