Activation of intrinsic hippocampal theta oscillations by acetylcholine inrat septo-hippocampal cocultures

1. Oscillatory electro-encephalographic activity at theta frequencies (4-15 Hz) can be recorded from the hippocampus in vivo and depends on intact sep tal projections. The hypothesis that these oscillations are imposed on the hippocampus by rhythmically active septal inputs was tested using dual. int racellular recordings from CA1 and CA3 pyramidal cells in septohippocampal cocultures. 2. Septo-hippocampal cocultures displayed spontaneous oscillatory synaptic activity at theta frequencies. In CA3 cells, EPSP/IPSP sequences predominat ed, whereas only EPSPs were apparent in CA1 cells. Synaptic potentials in C A3 cells preceded those in CA1 cells by 5-10 ms. 3. Oscillatory synaptic activity was blocked in cocultures by the muscarini c antagonist atropine (0.1 mu M), facilitated but unchanged in frequency up on application of the acetylcholinesterase inhibitor neostigmine (1 mu M), and not seen in hippocampal monocultures. 4. The muscarinic agonist methacholine (5-20 nM) induced oscillatory synapt ic activity at 4-15 Hz in hippocampal monocultures, which was identical to that occurring spontaneously in septo-hippocampal cocultures. 5. Synaptic theta activity was observed in cocultures of septal tissue with subdissected hippocampal slices containing area CA3 alone, but not in sept o-CA1. cocultures. 6. We conclude that oscillatory synaptic activity at theta frequencies, wit h similar characteristics to theta activity in vivo, can be generated by th e hippocampal network in response to activation of muscarinic receptors by synaptically released acetylcholine from septal afferents. Furthermore, the oscillatory activity is determined by mechanisms intrinsic to the hippocam pal circuitry, particularly area CA3. Rhythmic septal input is not required .