The slow afterhyperpolarization (sI_AHP) is a Ca²⁺-dependent K⁺ current that regulates hippocampal neuronal firing properties. The sI_AHP is responsible for accommodation of action potential firing during bursts of activity. Although the effects of the sI_AHP on cell firing properties is well characterised its effect on the behaviour of an oscillating network is unclear. The influence of the sI_AHP on gamma frequency oscillations (30-80 Hz) was investigated using mouse hippocampal slices.

All animals were humanely killed. Male adult mice were anaesthetised with inhaled isoflurane prior to intramuscular injection of ketamine (²ge³ 100 mg kg^-1) and xylazine (²ge³ 10 mg kg^-1). When all responses to noxious stimuli had terminated the animals were intracardially perfused with ~25 ml of modified artificial cerebrospinal fluid (ACSF) in which 126 mM NaCl was replaced with equiosmolar sucrose. Gamma frequency oscillations were induced by bath application of kainate (50-200 nM). Extracellular recordings were made from stratum radiatum/lacunosum-moleculare in the CA3 region. The power of the oscillation (the area from the power spectrum between 20-80 Hz) is expressed as mean percentage change ± S.E.M. Statistical significance was tested using either a paired t test or signed rank test.

The L-type calcium channel antagonist, nifedipine (10 µM), was bath applied to the established kainate-induced oscillation to decrease the sI_AHP. Nifedipine caused a trend to gradually increase the power of the gamma frequency oscillation, although this was not significant. After 15, 30 and 45 min application of nifedipine the power increased by 55 ± 28.3 % (n = 12; P > 0.05), 79 ± 23.7 % (n = 12; P > 0.05), and 101 ± 36.6 % (n = 10; P > 0.05) respectively. The frequency of the oscillation showed a significant reduction of 5 ± 2.6 % (n = 12; P < 0.05) after 30 min. The L-type calcium channel agonist, Bay K 8644 (1 µM) was bath applied to the established kainate-induced oscillation to increase the sI_AHP. After 15 min application there was a significant decrease in the power of the gamma frequency oscillation of 23 ± 5.1 % (n = 8; P < 0.01). A further significant decrease in power of 53 ± 6.5 % (n = 8; P < 0.01) was seen after 30 min application. However, there was no significant change in the frequency of the oscillation (P > 0.05).

These results suggest that modulation of the sI_AHP can affect kainate-induced gamma frequency activity. In particular the L-type calcium channel agonist Bay K 8644 significantly disrupted gamma oscillations. These results suggest that the sI_AHP has a direct effect on the behaviour of an oscillating network.

This work was supported by the MRC and Wellcome Trust.