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.
Original language | English (US) |
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Pages (from-to) | 119-137 |
Number of pages | 19 |
Journal | Neurobiology of Aging |
Volume | 49 |
DOIs | |
State | Published - Jan 1 2017 |
Bibliographical note
Funding Information:The authors thank Dr Isabel Sollozo-Dupont for participating in data evaluation, fitting selection, and statistical analysis. This work was supported by CONACYT –México grants to Emilio J. Galván: CB-2011-01-166241 and INFR-2012-01-187757 .
Publisher Copyright:
© 2016 Elsevier Inc.
Keywords
- Aging
- Feed-forward inhibition
- Frequency-dependent facilitation
- MF LTP
- MF-CA3 synapse
- PKA signaling cascade
ASJC Scopus subject areas
- General Neuroscience
- Aging
- Clinical Neurology
- Developmental Biology
- Geriatrics and Gerontology