Multiple cholinergic markers are unexpectedly not altered in the rat dentate gyrus following entorhinal cortex lesions.

Since major cholinergic deficits are observed in Alzheimer's disease, the development of models to study possible cholinergic plasticity has generated great interest. In this regard, it has been shown that lesions of the entorhinal cortex, which sends glutamatergic projections to the hippocampus, promote the sprouting and plasticity of presumptive cholinergic septohippocampal fibers in the dentate gyrus, as revealed by AChE histochemistry. This sprouting was reported to be evident at 8 d and up to 30 d postlesion (DPL) and is now widely used as a model of cholinergic neuronal plasticity. In the present study, unilateral lesions of the entorhinal cortex were made in adult rats, and the status of various putative pre- and postsynaptic cholinergic markers was assessed after 2, 4, 8, 14, and 30 DPL. As expected, AChE was increased in the outer molecular layer of the ipsilateral dentate gyrus from 8 to 30 DPL. In contrast, the activity of ChAT, the enzyme responsible for the synthesis of ACh, and the densities of specific binding sites for 3H-AH5 183/vesamicol (blocker of the ACh vesicular transport sites), 3H-hemicholinium-3 (blocker of the high-affinity choline uptake sites), muscarinic-M2 (3H-AF-DX 384 and 3H-ACh), muscarinic-M1 (3H-pirenzepine), and nicotinic (3H-N-methylcarbamylcholine) cholinergic receptors were not increased on the ipsilateral molecular layer of the dentate gyrus, as compared to their contralateral controls. We conclude that the increase in AChE staining in the molecular layer of the dentate gyrus following entorhinal cortex lesions may be due to changes in noncholinergic neurons.