title: Aging-related impairments of hippocampal mossy fibers synapses on CA3 pyramidal cells.
abstract: The network interaction between the dentate gyrus and area CA3 of the hippocampus is responsible for pattern separation, a process that underlies the formation of new memories, and which is naturally diminished in the aged brain. At the cellular level, aging is accompanied by a progression of biochemical modifications that ultimately affects its ability to generate and consolidate long-term potentiation. Although the synapse between dentate gyrus via the mossy fibers (MFs) onto CA3 neurons has been subject of extensive studies, the question of how aging affects the MF-CA3 synapse is still unsolved. Extracellular and whole-cell recordings from acute hippocampal slices of aged Wistar rats (34 ± 2 months old) show that aging is accompanied by a reduction in the interneuron-mediated inhibitory mechanisms of area CA3. Several MF-mediated forms of short-term plasticity, MF long-term potentiation and at least one of the critical signaling cascades necessary for potentiation are also compromised in the aged brain. An analysis of the spontaneous glutamatergic and gamma-aminobutyric acid-mediated currents on CA3 cells reveal a dramatic alteration in amplitude and frequency of the nonevoked events. CA3 cells also exhibited increased intrinsic excitability. Together, these results demonstrate that aging is accompanied by a decrease in the GABAergic inhibition, reduced expression of short- and long-term forms of synaptic plasticity, and increased intrinsic excitability.
authors: Departamento de Farmacobiología, Cinvestav Sede Sur, México City, México.
authors: Cindy
authors: C
authors: Villanueva-Castillo
authors: Departamento de Farmacobiología, Cinvestav Sede Sur, México City, México.
authors: Carolina
authors: C
authors: Tecuatl
authors: Departamento de Farmacobiología, Cinvestav Sede Sur, México City, México.
authors: Gabriel
authors: G
authors: Herrera-López
authors: Departamento de Farmacobiología, Cinvestav Sede Sur, México City, México. Electronic address: ejgalvan@cinvestav.mx.
authors: Emilio J
authors: EJ
authors: Galván
mesh_terms: D000375:Aging / Q000473:pathology* / Q000502:physiology*; D000818:Animals; D056654:CA3 Region, Hippocampal / Q000166:cytology* / Q000473:pathology* / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials; D007395:Interneurons; D017774:Long-Term Potentiation; D019599:Mossy Fibers, Hippocampal / Q000473:pathology* / Q000503:physiopathology*; D009473:Neuronal Plasticity; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000473:pathology* / Q000502:physiology; D017208:Rats, Wistar; D013569:Synapses / Q000473:pathology* / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D005680:gamma-Aminobutyric Acid
keywords: Aging; Feed-forward inhibition; Frequency-dependent facilitation; MF LTP; MF-CA3 synapse; PKA signaling cascade