Rhythmic oscillations in the entorhino-hippocampal system: biophysics and dynamics

New Jersey Institute Of Technology, Newark NJ

Investigators

Abstract

Rhythmic oscillations at various well identified frequency bands have been recorded in the brain using EEG (electroencephalogram) techniques during both wakefulness and sleep, and have been linked to various important cognitive and behavioral tasks. This project focuses on two of these rhythms, theta (4 - 12 Hz) and gamma (30 - 80 Hz), that have been observed in the hippocampus and the entorhinal cortex (EC), and have been implicated in learning, memory, spatial navigation and path integration (the ability to calculate a path on the basis of self motion cues). Using biophysical (conductance-based) modeling, dynamical systems techniques and computational simulations, the investigator explores how these rhythms emerge at the single cell and network leves, and what are their dynamic properties. The goal is to understand the basic dynamic and biophysical principles governing the generation of these rhythms over a wide spectrum of interacting levels of organization, ranging from the subcellular, through the cellular to the network leves, and how all this contributes to the functional role of these rhythmic oscillations. At the cellular level, the focus is on the so called stellate cells (SCs) from layer II of the medial EC that display mixed-mode oscillations (subthreshold oscillations interspersed with spikes) in the theta frequency regime. Using reduction of dimensions techniques we uncover a minimal biophysically plausible model that reproduces the observed mixed-mode oscillatory patterns. This model is both nonlinear and multi-scale. The study of its underlying dynamic structure, the so called canard structure, allows the investigator to understand how the observed patterns emerge from the interaction between a persistent sodium and a hyperpolarization-activated currents, as experimentally observed. This knowledge will be used to understand two important aspects of network activity: How SCs process structured information (sinusoidal, noisy and synaptic inputs), in particular how the intrinsic and synaptic currents interact to maintain the SC activity in the theta frequency regime, and how all these properties cooperate to generate rhythmic activity at theta and gamma frequencies in networks that include SCs along with interneurons, pyramidal cells and other cell types. More specifically, the questions of how and under what conditions the same network is able to generate theta and gamma rhythmic activity will be investigated, as well as how the abrupt transitions between both rhythms occur. Single SCs have the potential ability to spike in the gamma frequency regime, but the associated time scale is hidden in single isolated cells and it is uncover in the network level when the level of inhibition is deficient. This project addresses the general issue of how the brain is able to generate rhythmic activity at various frequency bands as the result of the biophysical properties of the networks that are substrate to these rhythms. A set of problems that are motivated by experimental results and are key to the understanding of the neural circuitries that are substrate to the observed rhythmic oscillations in the EC are considered. The results of this research provide valuable information about the biophysical mechanism of generation of these rhythms, not only in the EC, but also in the hippocampus where cells and networks with similar biophysical and dynamic properties can be found, and which receives direct inputs from the EC. In addition, the results will provide important insights into behavioral issues such as navigation where the theta rhythms in both the hippocampus and the EC plays a relevant role. Finally, this research will shed light into the role that the transition from theta to a hyper-excitable (gamma) frequency regime plays in the generation of epileptic seizures.