Aging-related impairments of hippocampal mossy fibers synapses on CA3 pyramidal cells
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- 作者：Cindy Villanueva-Castillo ; Carolina Tecuatl ; Gabriel Herrera-Ló ; pez ; Emilio J. Galvá ; n ; ejgalvan@cinvestav.mx
- 关键词：Aging ; MF-CA3 synapse ; Feed-forward inhibition ; Frequency-dependent facilitation ; MF LTP ; PKA signaling cascade
- 刊名：Neurobiology of Aging
- 出版年：2017
- 出版时间：January 2017
- 年：2017
- 卷：49
- 期：Complete
- 页码：119-137
- 全文大小：4492 K
- 卷排序：49
文摘
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.