A new neuronal target for β-amyloid peptide in the rat hippocampus.
In Alzheimer's disease, amyloid beta peptide (Aβ) accumulation is associated with hippocampal network dysfunction. Intrahippocampal injections of Aβ induce aberrant inhibitory septohippocampal (SH) network activity in vivo and impairment of memory processing. In the present study, we observed, after hippocampal Aβ 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 Aβ deposits. We observed that in Aβ-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 Aβ 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 Aβ, one of the main agents of dementia in Alzheimer's disease.
Centre de Psychiatrie et Neurosciences, UMR 894, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France. vincent.villette@inserm.fr
Vincent
V
Villette
Frédérique
F
Poindessous-Jazat
Brice
B
Bellessort
Elodie
E
Roullot
Yvan
Y
Peterschmitt
Jacques
J
Epelbaum
Aline
A
Stéphan
Patrick
P
Dutar
D000200:Action Potentials / Q000502:physiology; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D008297:Male; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D009474:Neurons / Q000473:pathology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides