Tubocurarine binding in undercut cerebral cortex and the effect of long-term electrical stimulation.

Several mechanisms have been proposed to explain prolonged epileptiform afterdischarge, elicited by various forms of stimulation in chronically isolated cerebral cortex: (1) loss of a muscarinic inhibitory mechanism 26, (2) decrease in the enzyme activity responsible for inactivating transmitter substance zl, (3) proliferation of axon collaterals 2°, (4) deafferentation of inhibitory stellate cells 2z, and (5) denervation (or 'disuse') supersensitivity to putative transmittersla, ~4. Which one or more of these is most implicated is still an open question. The last mechanism was investigated in the present study because it is related to epilepsy and to the theory of plasticity and learning in the central nervous system. Although undercut cortex is a deafferentated and deefferentated preparation, the characteristic loss of dendritic spines in the surviving neurons is a consequence of deafferentation 19 and of 'disuse' of synapses2L This interpretation is supported by Valverde's light deprivation studies 25. There are also instances of enhanced synaptic responses following deafferentation or disuse in the spinal cord1, 8. To test the hypothesis of disuse supersensitivity, we have taken advantage of two facts. First, it is possible to isolate fractions rich in 'cholinergic' synaptic membranes by the subcellular fractionation technique of De Robertis eta/ . 7,12, in which the isolated nerve ending complexes often have postsynaptic membranes attached. Second, changes in acetylcholine (ACh) receptor density in 'cholinergic' postsynaptic membranes can be indirectly detected by binding with cholinergic blocking agents such as tubocurarine 8. Using this approach we observed that the 'cholinergic' synaptic membranes of the undercut cortex bound more dimethyl-[14C]-D-tubocurarine than the corresponding membranes of the contralateral cortex. Furthermore, long-term electrical stimulation tended to prevent the elevation in binding noted in the undercut cortex.