Theta frequency (4 – 15 Hz) extracellular field activity can be reliably and repeatedly evoked in the medial septum/diagonal band of Broca (MS/DB) in vitro by the application of kainate. We have previously demonstrated a critical role for inhibitory neurotransmission in the maintenance of this activity and presented data that indicates parvalbumin GABAergic neurons are responsible for pacing rhythmic theta activity in the MS/DB. Evidence of functional electrical coupling between GABAergic interneurons has been reported in the hippocampus and neocortex and it has recently become clear that gap junctions may have a significant function in the generation of neuronal population activity. Here we demonstrate that application of the gap-junction uncoupling agent carbenoxolone causes a significant reduction (P< 0.05, Paired T test) in the kainate induced activity recorded at theta frequency (spectral integral in 4-15 Hz range) in the MS/DB slice in vitro.
MS/DB slices were prepared from male Wistar rats (21 days), which were terminally anaesthetised with pentobarbitone sodium (120 mg.kg-1, i.p.). The animals were transcardially perfused with ~ 25ml of modified ACSF and rapidly decapitated. Longitudinal slices (450 µm) were placed in an interface recording chamber and maintained at 32°C. Persistent theta oscillations were induced by bath application of 100 nM kainate. Carbenoxolone was bath applied to stabilized kainate induced activity at a concentration of 100 μM for 60 minutes. At 60 minutes there was a significant reduction in the theta frequency activity recorded (56.6% ± 2.3) and in peak amplitude (n = 6).
These results indicate a pivotal role for electrical signalling in the theta frequency rhythmic activity induced in the MS/DB upon application of kainate