Hippocampal sharp waves and ripples: Effects of aging and modulation by NMDA receptors and L-type Ca2+ channels.

Aging is accompanied by a complicated pattern of changes in the brain organization and often by alterations in specific memory functions. One of the brain activities with important role in the process of memory consolidation is thought to be the hippocampus activity of sharp waves and ripple oscillation (SWRs). Using field recordings from the CA1 area of hippocampal slices we compared SWRs as well as single pyramidal cell activity between adult (3-6-month old) and old (24-34-month old) Wistar rats. The slices from old rats displayed ripple oscillation with a significantly less number of ripples and lower frequency compared with those from adult animals. However, the hippocampus from old rats had significantly higher propensity to organized SWRs in long sequences. Furthermore, the bursts recorded from complex spike cells in slices from old compared with adult rats displayed higher number of spikes and longer mean inter-spike interval. Blockade of N-methyl-D-aspartic acid (NMDA) receptors by 3-((R)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) increased the amplitude of both sharp waves and ripples and increased the interval between events of SWRs in both age groups. On the contrary, CPP reduced the probability of occurrence of sequences of SWRs more strongly in slices from adult than old rats. Blockade of L-type voltage-dependent calcium channels by nifedipine only enhanced the amplitude of sharp waves in slices from adult rats. CPP increased the postsynaptic excitability and the paired-pulse inhibition in slices from both adult and old rats similarly while nifedipine increased the postsynaptic excitability only in slices from adult rats. We propose that the tendency of the aged hippocampus to generate long sequences of SWR events might represent the consequence of homeostatic mechanisms that adaptively try to compensate the impairment in the ripple oscillation in order to maintain the behavioral outcome efficient in the old individuals. The age-dependent alterations in the firing mode of pyramidal cells might underlie to some extent the changes in ripples that occur in old animals.