Cholinergic theta rhythm in transected hippocampal slices: independent CA1 and dentate generators

The controversy concerning intrahippocampal theta (theta) generators, arising as a result of in vivo investigations, prompted us to record theta-activity from isolated populations of CA1 pyramidal or dentate granule neurons in vitro. In the present study, transected slices (trans-slices) of the hippocampal formation were used to isolate the CA1 area from the dentate gyrus, providing a method for testing the 'two generator' hypothesis. We demonstrated that neurons in both the CA1 area and dentate gyrus could independently generate carbachol-induced (type 2) electroencephalogram (EEG) theta-activity. This activity could be completely blocked by the muscarinic receptor antagonist atropine sulfate but was unaffected by the nicotinic blocker, (+)-tubocurarine. These in vitro results provide the first direct evidence for the two-generator hypothesis and confirm the cholinergic-muscarinic nature of type 2 slow wave theta.