Effect of ageing on CA3 interneuron sAHP and gamma oscillations is activity-dependent.
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.
Lu
Cheng B
CB
School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Hamilton
James B
JB
Powell
Andrew D
AD
Toescu
Emil C
EC
Vreugdenhil
Martin
M
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D016257:Fura-2 / Q000494:pharmacology; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009553:Nimodipine / Q000494:pharmacology; D010507:Periodicity
D002120:Calcium Channel Agonists; D020746:Calcium Channels, L-Type; D002614:Chelating Agents; D018690:Excitatory Amino Acid Agonists; D009553:Nimodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D007608:Kainic Acid; D002118:Calcium; D016257:Fura-2