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

Neurobiol Aging. 2017 Jan;49:119-137. doi: 10.1016/j.neurobiolaging.2016.09.010. Epub 2016 Sep 28.

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.

Keywords: Aging; Feed-forward inhibition; Frequency-dependent facilitation; MF LTP; MF-CA3 synapse; PKA signaling cascade.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / pathology*
  • Aging / physiology*
  • Animals
  • CA3 Region, Hippocampal / cytology*
  • CA3 Region, Hippocampal / pathology*
  • CA3 Region, Hippocampal / physiopathology*
  • Excitatory Postsynaptic Potentials
  • Interneurons
  • Long-Term Potentiation
  • Mossy Fibers, Hippocampal / pathology*
  • Mossy Fibers, Hippocampal / physiopathology*
  • Neuronal Plasticity*
  • Patch-Clamp Techniques
  • Pyramidal Cells / pathology*
  • Pyramidal Cells / physiology
  • Rats, Wistar
  • Synapses / pathology*
  • Synapses / physiology*
  • gamma-Aminobutyric Acid / physiology

Substances

  • gamma-Aminobutyric Acid