Selective neurotoxins, chemical tools to probe the mind: the first thirty years and beyond

For centuries, starting with the advent of the microscope, cytotoxins have been known to non-selectively destroy nerves and other tissue cells. However, neurotoxins restricted in effect to one kind of neuron are an invention of the 20th century. One might reasonably trace the origins of this field to 1960 when the Nobel Laureates, R. Levi- Montalcini and S Cohen, showed that an antibody to nerve growth factor effectively prevented development of sympathetic nerves in the absence of overt changes in dorsal root ganglia and other neural and non-neural tissues. The year 1967 marks discovery of 6-hydroxydopamine, the first of dozens of chemically-selective neurotoxins. As stated by the physiologist W.B. Cannon, neural function can be deduced by denoting absence-deficits. A wealth of knowledge in neuroscience has been realized through use of neurotoxins. In the 21st century we foresee neurotoxins for virtually all neurochemically-identifiable or receptor-specific neurons, acting at/via functional proteins or characteristic DNA sites. These tools will provide us with a better means to probe the mind and thereby lead to a fuller understanding of the intricate roles of identifiable neuronal systems in integrative neuroscience.