ANALYSIS OF GAMMA-RHYTHMS IN THE RAT HIPPOCAMPUS IN-VITRO AND IN-VIVO

1. We have shown previously, with experimental and computer models, ho w a '40 Hz' (gamma) oscillation can arise in networks of hippocampal i nterneurones, involving mutual GABA(A)-mediated synaptic inhibition an d a source of tonic excitatory input. Here, we explore implications of this model for some hippocampal network phenomena in the rat in, vitr o and in vivo. 2. A model network was constructed of 1024 CA3 pyramida l cells and 256 interneurones. AMPA (alpha-amino-3-hydroxy-5-methyl-4- isoxazole propionic acid), NMDA (N-methyl-D-aspartate), GABA(A) and GA BA(B) receptors were simulated on pyramidal cells and on interneurones . 3. In both model and experiment, the frequency of network oscillatio ns, in the gamma range, depended upon three parameters: GABA(A) conduc tance and decay time constant in interneurone-->interneurone connectio ns, and the driving current to the interneurones. 4. The model of gamm a rhythm predicts an average zero phase lag between firing of pyramida l cells and interneurones, as observed in the rat hippocampus in vivo. The model also reproduces a gamma rhythm whose frequency changes with time, at theta frequency (about 5 Hz). This occurs when there is 5 Hz modulation of a tonic signal to chandelier and basket cells. 5. Synch ronized bursts can be produced in the model by several means, includin g partial blockade of GABA(A) receptors or of AMPA receptors on intern eurones, or by augmenting AMPA-mediated EPSCs. In all of these cases, the burst can be followed by a 'tail' of transiently occurring gamma w aves, a phenomenon observed in the hippocampus in vivo following sharp waves. This tail occurs in the model because of delayed excitation of the interneurones by the synchronized burst. A tail of gamma activity was found after synchronized epileptiform bursts both in the hippocam pal slice (CA3 region) and in vivo. 6. Our data suggest that gamma-fre quency EEG activity arises in the hippocampus when pools of interneuro nes receive a tonic or slowly varying excitation. The frequency of the oscillation depends upon the strength of this excitation and on the p arameters regulating the inhibitory coupling between the interneurones . The interneurone network output is then imposed upon pyramidal neuro nes in the form of rhythmic synchronized IPSPs.