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)|
|Number of pages||19|
|Journal||Neurobiology of Aging|
|State||Published - Jan 1 2017|
Bibliographical noteFunding 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 .
© 2016 Elsevier Inc.
- Feed-forward inhibition
- Frequency-dependent facilitation
- MF LTP
- MF-CA3 synapse
- PKA signaling cascade
ASJC Scopus subject areas
- Clinical Neurology
- Developmental Biology
- Geriatrics and Gerontology