Synaptic Noise and Physiological Coupling Generate High Frequency Oscillations in a 4 Hippocampal Computational Model

24 There is great interest in the role of coherent oscillations in the brain. In some cases, high 25 frequency oscillations (HFOs) are integral to normal brain function, while at other times they are 26 implicated as markers of epileptic tissue. Mechanisms underlying HFO generation, especially in 27 abnormal tissue, are not well understood. Using a physiological computer model of 28 hippocampus, we investigate random synaptic activity (noise) as a potential initiator of HFOs. 29 We explore parameters necessary to produce these oscillations, and quantify the response using 30 the tools of Stochastic Resonance (SR) and Coherence Resonance (CR). As predicted by SR, 31 when noise was added to the network the model was able to detect a subthreshold periodic 32 signal. Addition of basket cell interneurons produced two novel SR effects: 1) improved signal 33 detection at low noise levels and 2) formation of coherent oscillations at high noise that were 34 entrained to harmonics of the signal frequency. The periodic signal was then removed in order 35 to study oscillations generated only by noise. The combined effects of network coupling and 36 synaptic noise produced coherent, periodic oscillations within the network, an example of CR. 37 Our results show that, under normal coupling conditions, synaptic noise was able to produce 38 gamma (30-100 Hz) frequency oscillations. Synaptic noise generated HFOs in the ripple range 39 (100-200 Hz) when the network had parameters similar to pathological findings in epilepsy: 40 increased gap junction or recurrent synaptic connections, loss of inhibitory interneurons such as 41 basket cells, and increased synaptic noise. The model parameters that generated these effects are 42 comparable with published experimental data. We propose that increased synaptic noise and 43 physiological coupling mechanisms are sufficient to generate gamma oscillations, and that 44 pathologic changes in noise and coupling similar to those in epilepsy can produce abnormal 45 ripples. 46