A new neuronal target for beta-amyloid peptide in the rat hippocampus

In Alzheimer's disease, amyloid beta peptide (A beta) accumulation is associated with hippocampal network dysfunction. Intrahippocampal injections of A beta induce aberrant inhibitory septohippocampal (SH) network activity in vivo and impairment of memory processing. In the present study, we observed, after hippocampal A beta treatment, a selective loss of neurons projecting to the medial septum (MS) and containing calbindin (CB) and/or somatostatin (SOM). Other GABAergic neuronal subpopulations were not altered. Thus, the present study identifies hippocamposeptal neuron populations as specific targets for A beta deposits. We observed that in A beta-treated rats but not in controls, glutamate agonist application induced rhythmic bursting in 55% of the slow-firing neurons in the medial septum. This suggests that hippocampal A beta can trigger modifications of the septohippocampal pathway via the alteration of a specific neuronal population. Long-range hippocamposeptal GABA/calbindin neurons, targets of hippocampal amyloid deposits, are implicated in supporting network synchronization. By identifying this target, we contribute to the understanding of the mechanisms underlying deleterious effects of A beta, one of the main agents of dementia in Alzheimer's disease. (C) 2012 Elsevier Inc. All rights reserved.