Janssen WG, Andrews G, Tomey MI, Baxter MG, Morrison JH (2003) Combined bilateral perforant path lesions with lesions of the cholinergic system: an ultrastructural immunogold analysis of nmdar1 representation within the dentate gyrus. Neuroscience 2003 Abstracts 676.26. Society for Neuroscience, New Orleans, LA.
Summary: Alzheimer’s disease is characterized by deterioration of cholinergic input to the hippocampus, as well as degeneration of input from the entorhinal cortex to the dentate gyrus(DG). Studies have demonstrated an upregulation of the NMDA receptor subunit, NR1, following unilateral ablatement of the perforant path(pp). We hypothesized that cholinergic innervation might be essential for DG plasticity following pp ablation. Our study was designed to investigate the synaptic distribution of NR1 following combined 192 IgG-Saporin lesions of the medial septum/vertical diagonal band(MS/VDB) and bilateral(bilat) pp knife cut ablation. Animals received bilat-pp lesions 2-3 weeks days post MS/VDB and were sacrificed 17 days following pp lesion. Four groups of rats were tested: 1)MS-VDB with sham bilat-pp; 2)sham MS-VDB with bilat-pp; 3)MS-VDB with bilat-pp; 4)sham MS-VDB with sham bilat-pp. Using postembedding immunogold electron microscopy and SynBin, a program designed for quantification and compartmentalization of immunogold particles at the synaptic level, we investigated these effects in the outer molecular layer of the DG in a pilot study with 2 animals/group. Initial results suggest that the synaptic pools of NR1 within post-synaptic compartments were not affected with single MS/VDB, but that a long term synaptic down regulation of NR1 follows bilat pp lesion that is not affected by the additional removal of cholinergic input. While these combined lesions do not alter the pattern of synaptic NR1 receptor distribution following pp lesions, these data has important implications for lesion-induced hippocampal plasticity as well as structural and functional recovery.
Related Products: 192-IgG-SAP (Cat. #IT-01)