Decreased rhythmic GABAergic septal activity and memory-associated theta oscillations after hippocampal amyloid-beta pathology in the rat.
The memory deficits associated with Alzheimer's disease result to a great extent from hippocampal network dysfunction. The coordination of this network relies on theta (symbol) oscillations generated in the medial septum. Here, we investigated in rats the impact of hippocampal amyloid beta (Abeta) injections on the physiological and cognitive functions that depend on the septohippocampal system. Hippocampal Abeta injections progressively impaired behavioral performances, the associated hippocampal theta power, and theta frequency response in a visuospatial recognition test. These alterations were associated with a specific reduction in the firing of the identified rhythmic bursting GABAergic neurons responsible for the propagation of the theta rhythm to the hippocampus, but without loss of medial septal neurons. Such results indicate that hippocampal Abeta treatment leads to a specific functional depression of inhibitory projection neurons of the medial septum, resulting in the functional impairment of the temporal network.
Villette
Vincent
V
Inserm Centre de Psychiatrie et Neurosciences, Unité Mixte de Recherche 894, 75014 Paris, France. vincent.villette@inserm.fr
Poindessous-Jazat
Frédérique
F
Simon
Axelle
A
Léna
Clément
C
Roullot
Elodie
E
Bellessort
Brice
B
Epelbaum
Jacques
J
Dutar
Patrick
P
Stéphan
Aline
A
D000200:Action Potentials; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D016657:Cerebral Amyloid Angiopathy / Q000473:pathology / Q000503:physiopathology*; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008568:Memory / Q000502:physiology*; D009474:Neurons / Q000473:pathology / Q000502:physiology; D010507:Periodicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000502:physiology; D020665:Septum of Brain / Q000503:physiopathology*; D013028:Space Perception / Q000502:physiology; D013826:Theta Rhythm; D014796:Visual Perception / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D005680:gamma-Aminobutyric Acid