Electrical Stimulation on Synaptic Acetylcholinesterase

Partial or total isolation of the cerebral cortex was offered as a model for the study of focal epilepsy 6. After weeks or months the isolated cortex became sensitive to electrical stimulation or to topically applied acetylcholine (ACh) 5. Isolated cortex may also sustain prolonged epileptiform afterdischargeg, 2a. This is one measure of supersensitivity. A causal relationship between supersensitivity and an alteration in a cholinergic system has been suggested. This is based upon the observations that there is a decrease in acetylcholinesterase activity (ACHE) in isolated cortex11,16 and the decrease in AChE activity parallels the increase in supersensitivity 17. The expected development of supersensitivity in the partially isolated cerebral cortex may be prevented by long-term electrical stimulation of the undercut cortex z0. Further, the decrease in total AChE activity could also be prevented by the same procedure 4. These experiments suggest not only the involvement o fa cholinergic system in the supersensitivity of isolated cortex but also point to a critical feature, synaptic 'use' and 'disuse'. If it is assumed that isolation leads to 'disuse'iS, 2~, an important point to determine is whether changes in AChE activity occur at synaptic sites. Although AChE is highly concentrated in both preand postsynaptic membranes of cholinergic synapses la, it is also distributed in non-synaptic loci 1,15. This report attempts to define the specific intracellular locus of AChE activity changes in unstimulated undercut cerebral cortex (partial neuronal isolation) and in undercut cortex subjected to long-term electrical stimulation. Centrifugal fractionation of undercut cortical tissue localized the greatest change in activity of AChE in the subcellular fractions containing mainly cholinergic synaptic membranes.