ENHANCED ISOFLURANE SUPPRESSION OF EXCITATORY SYNAPTIC TRANSMISSION IN THE AGED RAT HIPPOCAMPUS

1 The effects of the volatile anaesthetic, isoflurane, were investigat ed on evoked dendritic field excitatory postsynaptic potentials (f.e.p .s.p.) and antidromic and orthodromic population spikes recorded extra cellularly in the CA1 cell layer region in the in vitro hippocampal sl ice taken from young mature (2-3 months) and old (24-27 months) Fisher 344 rats. 2 Isoflurane depressed the f.e.p.s.ps and the orthodromical ly-evoked population spikes in both old and young hippocampi. However, the magnitude of the anaesthetic-induced depression was greater in sl ices taken from old rats compared to those taken from young rats durin g the application of different isoflurane concentrations (0.5-5%). 3 I n the presence of the GABA(A) antagonist, bicuculline methiodide (15 m u M), isoflurane suppressed the f.e.p.s.ps to the same extent as was o bserved in the absence of the GABA(A) antagonist. 4 Orthodromically ev oked population spikes were suppressed by isoflurane in a manner quant itatively similar to the suppression of the f.e.p.s.ps. However, antid romic population spikes and presynaptic volleys evoked in young and ol d slices were resistant to anaesthetic action. In addition, paired pul se facilitation ratio of the evoked dendritic f.e.p.s.ps was not affec ted in both young and old slices during the application of isoflurane. 5 When slices were exposed to low Ca2+/high Mg2+ solution, isoflurane (1 and 3%) depressed the f.e.p.s.ps in aged slices to the same extent as in young slices. 6 The augmented anaesthetic depression of f.e.p.s .ps in old compared to young hippocampi in the absence and presence of bicuculline, and the lack of anaesthetic effects on antidromic popula tion spikes and presynaptic volleys in old and young slices, suggest t hat the increased sensitivity of anaesthetic actions in old hippocampi is due to age-induced attenuation of synaptic excitation rather than potentiation of synaptic inhibition. Furthermore, elimination of the i ncreased sensitivity of old slices to anaesthetic actions when the sli ces were perfused with low Ca2+/high Mg2+ medium, which presumably wou ld decrease intracellular [Ca2+], suggests that the enhanced anaesthet ic effects in aged neurones might be related to increased intraneurona l [Ca2+] in the synaptic terminal.