Neuronal Dynamics: from Complexity to Simplicity

An analytical study is performed to obtain the phase description of a network of Leaky Integrate-and-Fire (LIF) neurons. We start by discussing the behaviour of single LIF neuron in the presence of a constant current and then derive the corresponding phase oscillator model for some parameters setup. In the case of two identical LIF neurons where the interactions are ruled by the weak pulse input, we determine the analytical expression for the phase response curve. Next, we extend the phase reduction principles to a generic case of N networks of identical LIF neurons. The final model of so-called phase oscillators is widely used to study synchronization in many natural systems. Through numerical simulations, we find an agreement between the LIF neurons and the phase oscillators model.

Semi-passivity and synchronization of diffusively coupled neuronal oscillators

We discuss synchronization in networks of neuronal oscillators which are interconnected via diffusive coupling, i.e. linearly coupled via gap junctions. In particular, we present sufficient conditions for synchronization in these networks using the theory of semi-passive and passive systems. We show that the conductance-based neuronal models of Hodgkin-Huxley, Morris-Lecar, and the popular reduced models of FitzHugh-Nagumo and Hindmarsh-Rose all satisfy a semi-passivity property, i.e. that is the state trajectories of such a model remain oscillatory but bounded provided that the supplied (electrical) energy is bounded. As a result, for a wide range of coupling configurations, networks of these oscillators are guaranteed to possess ultimately bounded solutions. Moreover, we demonstrate that when the coupling is strong enough the oscillators become synchronized. Our theoretical conclusions are confirmed by computer simulations with coupled \HR and \ML oscillators. Finally we discuss possible "instabilities" in networks of oscillators induced by the diffusive coupling

Multi-Stability and Pattern-Selection in Oscillatory Networks with Fast Inhibition and Electrical Synapses

A model or hybrid network consisting of oscillatory cells interconnected by inhibitory and electrical synapses may express different stable activity patterns without any change of network topology or parameters, and switching between the patterns can be induced by specific transient signals. However, little is known of properties of such signals. In the present study, we employ numerical simulations of neural networks of different size composed of relaxation oscillators, to investigate switching between in-phase (IP) and anti-phase (AP) activity patterns. We show that the time windows of susceptibility to switching between the patterns are similar in 2-, 4- and 6-cell fully-connected networks. Moreover, in a network (N = 4, 6) expressing a given AP pattern, a stimulus with a given profile consisting of depolarizing and hyperpolarizing signals sent to different subpopulations of cells can evoke switching to another AP pattern. Interestingly, the resulting pattern encodes the profile of the switching stimulus. These results can be extended to different network architectures. Indeed, relaxation oscillators are not only models of cellular pacemakers, bursting or spiking, but are also analogous to firing-rate models of neural activity. We show that rules of switching similar to those found for relaxation oscillators apply to oscillating circuits of excitatory cells interconnected by electrical synapses and cross-inhibition. Our results suggest that incoming information, arriving in a proper time window, may be stored in an oscillatory network in the form of a specific spatio-temporal activity pattern which is expressed until new pertinent information arrives

Molecular mechanisms that regulate the coupled period of the mammalian circadian clock

In mammals, most cells in the brain and peripheral tissues generate circadian (~24hr) rhythms autonomously. These self-sustained rhythms are coordinated and entrained by a master circadian clock in the suprachiasmatic nucleus (SCN). Within the SCN, the individual rhythms of each neuron are synchronized through intercellular signaling. One important feature of SCN is that the synchronized period is close to the cell population mean of intrinsic periods. In this way, the synchronized period of the SCN stays close to the periods of cells in peripheral tissues. This is important for SCN to entrain cells throughout the body. However, the mechanism that drives the period of the coupled SCN cells to the population mean is not known. We use mathematical modeling and analysis to show that the mechanism of transcription repression plays a pivotal role in regulating the coupled period. Specifically, we use phase response curve analysis to show that the coupled period within the SCN stays near the population mean if transcriptional repression occurs via protein sequestration. In contrast, the coupled period is far from the mean if repression occurs through highly nonlinear Hill-type regulation (e.g. oligomer- or phosphorylation-based repression). Furthermore, we find that the timescale of intercellular coupling needs to be fast compared to that of intracellular feedback to maintain the mean period. These findings reveal the important relationship between the intracellular transcriptional feedback loop and intercellular coupling. This relationship explains why transcriptional repression appears to occur via protein sequestration in multicellular organisms, mammals and Drosophila, in contrast with the phosphorylation-based repression in unicellular organisms. That is, transition to protein sequestration is essential for synchronizing multiple cells with a period close to the population mean (~24hr).Comment: 21 pages, 16 figure