Gamma frequency oscillations (30-80 Hz) can be evoked in the hippocampal slice by a number of methods, including bath application of either carbachol or kainate. This gamma frequency network activity is dependent on both electrical and chemical interactions and is abolished by the gap junction blockers octanol and carbenoxolone – indicating dependence upon gap junction conductances. However, computer modelling has predicted that as long as there is a high level of ectopic action potential activity in principal cell axons, gap junctions are not essential for this pharmacological gamma frequency activity (Traub et al. 2000). Gap junctional dependence of kainate induced gamma frequency oscillations 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 (▓ge│ 100 mg kg^-1) and xylazine (▓ge│ 10 mg kg^-1). When all response to noxious stimuli, such as pedal withdrawal reflex, had terminated, the animals were intracardially perfused with ~25 ml of modified artificial cerebrospinal fluid (ACSF). Slices were maintained at 34°C at the interface between oxygenated ACSF and a mixture of 95 % O₂ and 5 % CO₂. Gamma oscillations were induced using kainate (200-300 nM) and the potassium channel blocker, 4-amino-pyridine (4-AP), was applied to increase neuronal and axonal excitability. When carbenoxolone (100 mM) was bath applied to established kainate-induced oscillations there was a 90 ± 3.42 % block of gamma frequency activity within 60 min (n = 8). However, in contrast, carbenoxolone failed to cause a complete block of the oscillatory activity when in the presence of 40 mM 4-AP (n = 6). In fact 15-30 min application of carbenoxolone caused an increase in oscillatory power of 130 ± 82.2 % (n = 6). At 60 min carbenoxolone had still not fully abolished the oscillation, which was at 35 ± 45.1 % compared with kainate and 40 mM 4-AP. This suggests that partial block of gap junctions was able to produce a recovery of the gamma oscillation. With a longer application time carbenoxolone did decrease the activity but it was never completely abolished. This indicates that 4-AP was able to sufficiently increase axonal excitability such that gap junctions were no longer essential for the maintenance of the gamma frequency oscillation.

This work was funded by the Medical Research Council.

All procedures accord with current UK legislation.