Effect of ageing on CA3 interneuron sAHP and gamma oscillations is activity-dependent

Neurobiol Aging. 2011 May;32(5):956-65. doi: 10.1016/j.neurobiolaging.2009.05.006. Epub 2009 Jun 11.

Abstract

Normal ageing-associated spatial memory impairment has been linked to subtle changes in the hippocampal network. Here we test whether the age-dependent reduction in gamma oscillations can be explained by the changes in intrinsic properties of hippocampal interneurons. Kainate-induced gamma oscillations, but not spontaneous gamma oscillations, were reduced in slices from aged mice. CA3 interneurons were recorded in slices from young and aged mice using Fura-2-filled pipettes. Passive membrane properties, firing properties, medium- and slow-afterhyperpolarisation amplitudes, basal [Ca(2+)](i) and firing-induced [Ca(2+)](i) transients were not different with ageing. Kainate caused a larger depolarisation and increase in [Ca(2+)](i) signal in aged interneurons than in young ones. In contrast to young interneurons, kainate increased the medium- and slow-afterhyperpolarisation and underlying [Ca(2+)](i) transient in aged interneurons. Modulating the slow-afterhyperpolarisation by modulating L-type calcium channels with BAY K 8644 and nimodipine suppressed and potentiated, respectively, kainate-induced gamma oscillations in young slices. The age-dependent and stimulation-dependent increase in basal [Ca(2+)](i), firing-induced [Ca(2+)](i) transient and associated afterhyperpolarisation may reduce interneuron excitability and contribute to an age-dependent impairment of hippocampal gamma oscillations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Aging / drug effects
  • Aging / physiology*
  • Animals
  • CA3 Region, Hippocampal / drug effects
  • CA3 Region, Hippocampal / physiology*
  • Calcium / physiology
  • Calcium Channel Agonists / pharmacology
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, L-Type / pharmacology
  • Chelating Agents / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology
  • Fura-2 / pharmacology
  • Interneurons / drug effects
  • Interneurons / physiology*
  • Kainic Acid / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mice
  • Mice, Inbred C57BL
  • Nimodipine / pharmacology
  • Periodicity

Substances

  • Calcium Channel Agonists
  • Calcium Channels, L-Type
  • Chelating Agents
  • Excitatory Amino Acid Agonists
  • Nimodipine
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Kainic Acid
  • Calcium
  • Fura-2