Macroscopic phase resetting-curves determine oscillatory coherence and signal transfer in inter-coupled neural circuits

Macroscopic oscillations of different brain regions show multiple phase relationships that are persistent across time and have been implicated in routing information. While multiple cellular mechanisms influence the network oscillatory dynamics and structure the macroscopic firing motifs, one of the key questions is to identify the biophysical neuronal and synaptic properties that permit such motifs to arise. A second important issue is how the different neural activity coherence states determine the communication between the neural circuits. Here we analyse the emergence of phase-locking within bidirectionally delayed-coupled spiking circuits in which global gamma band oscillations arise from synaptic coupling among largely excitable neurons. We consider both the interneuronal (ING) and the pyramidal-interneuronal (PING) population gamma rhythms and the inter coupling targeting the pyramidal or the inhibitory neurons. Using a mean-field approach together with an exact reduction method, we reduce each spiking network to a low dimensional nonlinear system and derive the macroscopic phase resetting-curves (mPRCs) that determine how the phase of the global oscillation responds to incoming perturbations. This is made possible by the use of the quadratic integrate-and-fire model together with a Lorentzian distribution of the bias current. Depending on the type of gamma (PING vs. ING), we show that incoming excitatory inputs can either speed up the macroscopic oscillation (phase advance; type I PRC) or induce both a phase advance and a delay (type II PRC). From there we determine the structure of macroscopic coherence states (phase-locking) of two weakly synaptically-coupled networks. To do so we derive a phase equation for the coupled system which links the synaptic mechanisms to the coherence states of the system. We show that a synaptic transmission delay is a necessary condition for symmetry breaking, i.e. a non-symmetric phase lag between the macroscopic oscillations. This potentially provides an explanation to the experimentally observed variety of gamma phase-locking modes. Our analysis further shows that symmetry-broken coherence states can lead to a preferred direction of signal transfer between the oscillatory networks where this directionality also depends on the timing of the signal. Hence we suggest a causal theory for oscillatory modulation of functional connectivity between cortical circuits. Author summary Large scale brain oscillations emerge from synaptic interactions within neuronal circuits. Over the past years, such macroscopic rhythms have been suggested to play a crucial role in routing the flow of information across cortical regions, resulting in a functional connectome. The underlying mechanism is cortical oscillations that bind together following a well-known motif called phase-locking. While there is significant experimental support for multiple phase-locking modes in the brain, it is still unclear what is the underlying mechanism that permits macroscopic rhythms to phase lock. In the present paper we take up with this issue, and to show that, one can study the emergent macroscopic phase-locking within the mathematical framework of weakly coupled oscillators. We find that under synaptic delays, fully symmetrically coupled networks can display symmetry-broken states of activity, where one network starts to lead in phase the second (also sometimes known as stuttering states). When we analyse how incoming transient signals affect the coupled system, we find that in the symmetry-broken state, the effect depends strongly on which network is targeted (the leader or the follower) as well as the timing of the input. Hence we show how the dynamics of the emergent phase-locked activity imposes a functional directionality on how signals are processed. We thus offer clarification on the synaptic and circuit properties responsible for the emergence of multiple phase-locking patterns and provide support for its functional implication in information transfer.