Properties and distribution of an active cerebellar factor

Abstract

1. A technique for the introduction of substances into the cerebellum of the decerebrate rabbit was developed and the effects of drugs and brain extracts on the electrical activity of the cerebellum were studied using this method. 2. Extracts of cerebellar tissue were found to increase the electrical activity of the cerebellum and this action could not be attributed to Ach, histamine or to any other identified pharmacologically-active constituent of the nervous system, nor could it be attributed to a vascular action. The activity was not detected in similar concentrations in extracts of cerebral hemispheres or upper brain-stem. 3. The physical and chemical properties of the cerebellar excitatory substance were studied and attempts to purify it from crude brain extracts were made. 4. The enzymic destruction of the active factor was demonstrated and this destruction was shown to be inhibited by small amounts of strychnine. The active substance was found to be released from the cerebellum under various conditions of stimulation. 5. The active substance had no apparent effect on any of the common pharmecological preparations, not did it affect transmission at the neuromuscular junction and superior cervical ganglion. 6. The cerebellar factor was found to affect spinal reflexes and the electrical activity of the cerebral cortex. 7. Nervous tissue from six animal species was found to contain the active substance, but it was not detected in similar concentrations in tissues outside the nervous system. Its distribution in various regions of the nervous system of the dog was shown to bear an approximately inverse relationship to the distribution of choline acetylase activity and acetylcholine. 8. It has been suggested that the cerebellar factor has some claims to be considered as a non-colinergic transmitter of nerve impulses and experiments which might eventually confirm this hypothesis have been considered.