REGULATION OF 1,4,5-IP3, 1,3,4,5-IP4 AND IP6 BINDING-SITES FOLLOWING ENTORHINAL CORTEX LESIONS IN RAT-BRAIN

A lesion of the entorhinal cortex produces a loss of more than 80% of the synapses in the outer molecular layer of the hippocampus in the ra t. However, this synaptic loss is transient. Beginning a few days afte r denervation, new synapses are formed, virtually replacing the lost i nputs within two months. Synaptic remodelling induced by entorhinal co rtex lesion is associated with specific modifications of various neuro transmitters, hormones and growth factors. Many of these substances ac t at membrane bound-receptors to induce the hydrolysis of phosphatidyl inositols generating Various inositol phosphates. Some of the key memb ers of this family include inositol 1,4,5-trisphosphate inositol 1,3,4 ,5-tetrakisphosphate and inositol hexakisphosphate which are all assoc iated with the maintenance Ca2+ homeostasis. To investigate the potent ial roles and/or alterations of inositol phosphates in entorhinal cort ex lesions-induced neuronal plasticity, we quantified specific recepto r sites for inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakispho sphate and inositol hexakisphosphate using their respective tritiated ligands, at different periods post-lesion corresponding to the degener ative and subsequent reinnervation phases. [H-3]inositol 1,4,5-trispho sphate binding sites are maximally increased (30%) between two and eig ht days post-lesion in the hippocampal formation on both sides of the lesion. In the cortex, [H-3]inositol 1,4,5-trisphosphate binding incre ased also bilaterally following the lesion. Changes in [H-3]inositol 1 ,3,4,5-tetrakisphosphate binding are delayed and reduced (20% increase ) in magnitude compared to these seen for [H-3]inositol 1,4,5-trisphos phate binding. The maximal peak in [H-3]inositol 1,3,4,5-tetrakisphosp hate binding is observed between eight and 14 days after the lesion in the hippocampal formation and the cortex. On the other hand, decrease s in [H-3]inositol hexakisphosphate binding (up to 30%) in the parieta l cortex and the pyramidal cell layer of the hippocampal formation wer e observed between 14 and 30 days post-lesion. Taken together, these r esults suggest that inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tet rakisphosphate and inositol hexakisphosphate receptors can be regulate d in vivo following entorhinal cortex lesions. A unique time course is observed for each inositol phosphate receptor site studied. This find ing supports the hypothesis suggesting that each inositide is differen tially involved in the process of neuronal plasticity observed followi ng deafferentation in the entorhinal cortex of rats. The bilateral cha nges in unilaterally lesioned animals is consistent with secondary syn apse turnover associated with deafferentation.