Bilateral changes in glutamate uptake,muscarinic receptor binding and acetylcholinesterase level in the rat hippocampus after unilateral entorhinal cortex lesions

This report examines the effects of unilateral electrolytic and knife-cut lesions of entorhinal cortex on glutamate uptake, the muscarinic receptor ³H]QNB binding and acetylcholinesterase (AChE) activity in the dorsal and ventral parts of the ipsi- and contralateral hippocampus of the rat.We found that (1) in unoperated, control rats there are no pre-existing differences in the level of the investigated markers between the right and left hippocampus, (2) both electrolytic and knife-cut lesions of the entorhinal cortex evoke bilateral changes in the investigated markers and (3) the character of the response is dependent on the survival time and on the hippocampal part involved. Four days after operation a substantial reduction in glutamate uptake was found in both the dorsal and ventral parts of the ipsi- and contralateral hippocampus. At the same time there was a drop in muscarinic receptor binding, while AChE activity was not affected. The decrease in glutamate uptake persisted on the 21st postoperative day, whereas muscarinic receptor binding was enhanced, in comparison with the control level, in the ventral part of both the ipsi- and contralateral hippocampus. This overshoot was not so evident on the 30th postoperative day; glutamate uptake at that time reached or even surpassed the control level. Enhancement of AChE activity on the ipsi- and contralateral sides was noted on both the 21st and 30th day after operation.We suggest the following interpretation of these results: (1) glutamatergic projections from the entorhinal cortex to the hippocampus are bilateral, (2) some transneuronal changes probably contribute to the decline in glutamate uptake, particularly on the contralateral side, (3) neuronal depolarization does not seem to be the only mechanism responsible for the decrease in muscarinic receptor binding and (4) some compensatory mechanisms occur in the hippocampus at a later time after the lesion.Moreover, we believe that the use of the contralateral side as a control should be considered with caution in studies with unilaterally lesioned animals.