Four Criteria Define A Neurotransmitter

The ideas defining a neurotransmitter have changed over the past century as a consequence of growing knowledge of cell biology, pharmacology, and electro-physiology. As late as 1940, there was debate about whether chemical transmission plays any role in synaptic transmission. Some investigators, John C. Eccles among them, believed that all synaptic signals were electrical. By midcentury, however, everyone agreed that there are two forms of transmission, chemical and electrical. Eccles had changed his mind to become one of the foremost investigators of the physiology of synapses.

Most influential was a simple experiment performed by Otto Loewi in 1921. It was known that the heartbeat is slowed when the vagus nerve is stimulated. In order to prove that a diffusable substance is released upon stimulation, Loewi bathed two frog hearts in a physiological saline solution. Both hearts beat at a normal rate. Then he stimulated the vagus nerve to one of the hearts. That heart slowed, as expected. But the heart with the unstimulated vagus also slowed, indicating that a substance, which Loewi called Vagusstoffe, was released into the bath to slow the other heart. Soon afterward, Vagusstoffe was identified as acetylcholine (ACh), a substance previously found in high concentrations in nervous systems. Long afterward, Loewi told the story about how this influential experiment occurred to him in dreams on two successive nights. In an autobiographical sketch, he tells how the design for the experiment came to him on the first night but was forgotten when he awoke. On the next night, he made sure he had pencil and paper ready and successfully noted the protocol of the dream experiment.

Two of the four criteria used today for deciding whether a substance is in fact a neurotransmitter are suggested by Loewi's experiment: (1) the substance must be synthesized by the neuron, and (2) the substance must be concentrated in nerve terminals and released when the neuron is stimulated. The amount of transmitter released should, of course, be sufficient to affect the postsynaptic neuron or target cell. The third criterion is pharmacological: (3) the putative transmitter must mimic the action of the substance released from the neuron when applied to the target cell in reasonable concentrations.

The last requirement reflects an important aspect of synaptic transmission: (4) mechanisms must exist for removing the putative transmitter from its target. Removal of the released transmitter is a requirement for transmitting a meaningful message. Failure to remove the transmitter would result either in a persistently activated postsynaptic element or, more commonly, a block of transmission because of post-synaptic receptor desensitization.

Anxiety and Depression 101

Anxiety and Depression 101

Everything you ever wanted to know about. We have been discussing depression and anxiety and how different information that is out on the market only seems to target one particular cure for these two common conditions that seem to walk hand in hand.

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