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Accelerated aging of the GABAergic septohippocampal pathway and decreased hippocampal rhythms in a mouse model of Alzheimer's disease
Author(s) -
Rubio Sara E.,
VegaFlores Germán,
Martínez Albert,
Bosch Carles,
PérezMediavilla Alberto,
Río Joaquín del,
Gruart Agnès,
DelgadoGarcía José María,
Soriano Eduardo,
Pascual Marta
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.12-208413
Subject(s) - gabaergic , hippocampal formation , neuroscience , cholinergic , hippocampus , biology , inhibitory postsynaptic potential
Patients with Alzheimer's disease (AD) display altered functioning of cortical networks, including altered patterns of synchronous activity and a serious deficit in cholinergic septohippocampal (SH) innervation. However, the mechanisms underlying these alterations and the implication of the GABAergic SH component in AD are largely unknown. In addition, the GABAergic septohippocampal pathway (SHP) is believed to regulate synchronous hippocampal activity by controlling the activity of interneurons. Here we show, using well‐characterized pathway tracing experiments, that innervation of the GABAergic SHP decreases during normal aging. Furthermore, in an AD mouse model (hAPP Sw,Ind ; J20 mice), the GABAergic SHP shows a dramatic and early onset of this decrease in 8‐mo‐old mice. This decline is not caused by neuronal loss, but by the reduced number and complexity of GABAergic SH axon terminals. Finally, we demonstrate that hippocampal θ and γ rhythm power spectra are markedly diminished in 8‐mo‐old behaving mice expressing mutated hAPP. In addition to the well‐known loss of cholinergic input to the hippocampus in AD, these data suggest that the altered patterns of synchronous activity seen in patients with AD could be caused by the loss of GABAergic SH axons, which modulate hippocampal network activities.—Rubio, S. E., Vega‐Flores, G., Martínez, A., Bosch, C., Pérez‐Mediavilla, A., del Río, J., Gruart, A., Delgado‐García, J. M., Soriano, E., Pascual, M. Accelerated aging of the GABAergic septohippocampal pathway and decreased hippocampal rhythms in a mouse model of Alzheimer's disease. FASEB J. 26, 4458–4467 (2012). www.fasebj.org