Theta-gamma phase amplitude coupling in a hippocampal CA1 microcircuit

Author summaryOscillations are a prominent and ubiquitous feature of brain operations. They are found across multiple different animal species and with a variety of recording techniques from small-scale microelectrodes up to large-scale EEG and fMRI. Oscillations appear in a range of discrete frequencies, such as theta (3-8 Hz) and gamma (25-100 Hz) in the hippocampus. Notably, these oscillations are found to be coupled whereby the phase of the slower oscillation modulates the amplitude of the faster oscillation. The strength of this 'phase-amplitude coupling' is itself found to depend on the animals cognitive state and ongoing behaviour, and is therefore thought to play an important functional role. Despite the importance of this phenomenon, its biophysical origin and the reasons for its ubiquity across brain regions and species remain unclear. Here, using a data-driven physiologically detailed computational model of hippocampal CA1, we show how a basic microcircuit can autonomously generate both theta and gamma which are phase-amplitude coupled. The results suggests that the underlying dynamical mechanism is very general, and will be relevant in multiple different neural settings. Phase amplitude coupling (PAC) between slow and fast oscillations is found throughout the brain and plays important functional roles. Its neural origin remains unclear. Experimental findings are often puzzling and sometimes contradictory. Most computational models rely on pairs of pacemaker neurons or neural populations tuned at different frequencies to produce PAC. Here, using a data-driven model of a hippocampal microcircuit, we demonstrate that PAC can naturally emerge from a single feedback mechanism involving an inhibitory and excitatory neuron population, which interplay to generate theta frequency periodic bursts of higher frequency gamma. The model suggests the conditions under which a CA1 microcircuit can operate to elicit theta-gamma PAC, and highlights the modulatory role of OLM and PVBC cells, recurrent connectivity, and short term synaptic plasticity. Surprisingly, the results suggest the experimentally testable prediction that the generation of the slow population oscillation requires the fast one and cannot occur without it.

Automated summary

Oscillations are a common feature of brain operations and are found across different animal species. These oscillations appear in discrete frequencies and are coupled, with the phase of one oscillation modulating the amplitude of another. However, the biophysical origin and reasons for the ubiquity of these oscillations remain unclear. Using a data-driven computational model, researchers demonstrate how a basic microcircuit can generate phase-amplitude coupled oscillations, suggesting a general underlying mechanism.