Aging-related impairments of hippocampal mossy fibers synapses on CA3 pyramidal cells

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 bioche...

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Veröffentlicht in:Neurobiology of aging 2017-01, Vol.49, p.119-137
Hauptverfasser: Villanueva-Castillo, Cindy, Tecuatl, Carolina, Herrera-López, Gabriel, Galván, Emilio J.
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container_title Neurobiology of aging
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creator Villanueva-Castillo, Cindy
Tecuatl, Carolina
Herrera-López, Gabriel
Galván, Emilio J.
description 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.
doi_str_mv 10.1016/j.neurobiolaging.2016.09.010
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subjects Aging
Aging - pathology
Aging - physiology
Animals
CA3 Region, Hippocampal - cytology
CA3 Region, Hippocampal - pathology
CA3 Region, Hippocampal - physiopathology
Excitatory Postsynaptic Potentials
Feed-forward inhibition
Frequency-dependent facilitation
gamma-Aminobutyric Acid - physiology
Interneurons
Long-Term Potentiation
MF LTP
MF-CA3 synapse
Mossy Fibers, Hippocampal - pathology
Mossy Fibers, Hippocampal - physiopathology
Neuronal Plasticity
Patch-Clamp Techniques
PKA signaling cascade
Pyramidal Cells - pathology
Pyramidal Cells - physiology
Rats, Wistar
Synapses - pathology
Synapses - physiology
title Aging-related impairments of hippocampal mossy fibers synapses on CA3 pyramidal cells
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