Sequential activation of neurons that occurs during “offline” states, such as sleep or awake rest, is correlated with neural sequences recorded during preceding exploration phases. This so-called reactivation, or replay, has been observed in a number of different brain regions such as the striatum, prefrontal cortex, primary visual cortex and, most prominently, the hippocampus. Reactivation largely co-occurs together with hippocampal sharp-waves/ripples, brief high-frequency bursts in the local field potential. Here, we first review the mounting evidence for the hypothesis that reactivation is the neural mechanism for memory consolidation during sleep. We then discuss recent results that suggest that offline sequential activity in the waking state might not be simple repetitions of previously experienced sequences. Some offline sequential activity occurs before animals are exposed to a novel environment for the first time, and some sequences activated offline correspond to trajectories never experienced by the animal. We propose a conceptual framework for the dynamics of offline sequential activity that can parsimoniously describe a broad spectrum of experimental results. These results point to a potentially broader role of offline sequential activity in cognitive functions such as maintenance of spatial representation, learning, or planning.

Anaesthetic agents are known to affect extra-synaptic GABAergic receptors, which induce tonic inhibitory currents. Since these receptors are very sensitive to small concentrations of agents, they are supposed to play an important role in the underlying neural mechanism of general anaesthesia. Moreover anaesthetic agents modulate the encephalographic activity (EEG) of subjects and hence show an effect on neural populations. To understand better the tonic inhibition effect in single neurons on neural populations and hence how it affects the EEG, the work considers single neurons and neural populations in a steady-state and studies numerically and analytically the modulation of their firing rate and nonlinear gain with respect to different levels of tonic inhibition. We consider populations of both type-I (Leaky Integrate-and-Fire model) and type-II (Morris-Lecar model) neurons. To bridge the single neuron description to the population description analytically, a recently proposed statistical approach is employed which allows to derive new analytical expressions for the population firing rate for type-I neurons. In addition, the work shows the derivation of a novel transfer function for type-I neurons as considered in neural mass models and studies briefly the interaction of synaptic and extra-synaptic inhibition. We reveal a strong subtractive and divisive effect of tonic inhibition in type-I neurons, i.e. a shift of the firing rate to higher excitation levels accompanied by a change of the nonlinear gain. Tonic inhibition shortens the excitation window of type-II neurons and their populations while maintaining the nonlinear gain. The gained results are interpreted in the context of recent experimental findings under propofol-induced anaesthesia.

Mathematical modeling is a powerful tool that enables researchers to describe the experimentally observed dynamics of complex systems. Starting with a robust model including model parameters, it is necessary to choose an appropriate set of model parameters to reproduce experimental data. However, estimating an optimal solution of the inverse problem, i.e., finding a set of model parameters that yields the best possible fit to the experimental data, is a very challenging problem. In the present work, we use different optimization algorithms based on a frequentist approach, as well as Monte Carlo Markov Chain methods based on Bayesian inference techniques to solve the considered inverse problems. We first probe two case studies with synthetic data and study models described by a stochastic non-delayed linear second-order differential equation and a stochastic linear delay differential equation. In a third case study, a thalamo-cortical neural mass model is fitted to the EEG spectral power measured during general anesthesia induced by anesthetics propofol and desflurane. We show that the proposed neural mass model fits very well to the observed EEG power spectra, particularly to the power spectral peaks within δ - (0 - 4 Hz) and α - (8 - 13 Hz) frequency ranges. Furthermore, for each case study, we perform a practical identifiability analysis by estimating the confidence regions of the parameter estimates and interpret the corresponding correlation and sensitivity matrices. Our results indicate that estimating the model parameters from analytically computed spectral power, we are able to accurately estimate the unknown parameters while avoiding the computational costs due to numerical integration of the model equations.