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

Cindy Villanueva-Castillo, Carolina Tecuatl, Gabriel Herrera-López, Emilio J. Galván*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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 languageEnglish (US)
Pages (from-to)119-137
Number of pages19
JournalNeurobiology of Aging
StatePublished - Jan 1 2017


  • Aging
  • Feed-forward inhibition
  • Frequency-dependent facilitation
  • MF LTP
  • MF-CA3 synapse
  • PKA signaling cascade

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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