Desvendando oscilações hipocampais através de comodulações

Abstract

Spectral analysis of extracellular electrophysiological recordings revealed that the brain electrical activity is often organized in rhythmic patterns, known as neuronal oscillations. Recently, it was discovered that oscillations of distinct frequencies are not independent, but can interact to each other. In the last two decades, several analysis tools were developed or incorporated from other fields to study cross-frequency coupling between neural oscillations. Neural oscillations are said to be coupled if there is a dependency between their features, such as phase, amplitude or frequency. Among them, phase – amplitude coupling is characterized by an increase in the instantaneous amplitude of one frequency band conditioned to the instantaneous phase of another frequency band, whereas n:m phase – phase coupling is characterized by a fixed relation between m cycles of one frequency to n cycles of another one. The hippocampus is a brain region involved in memory formation and spatial navigation. As in other brain structures, hippocampal neural networks generate several oscillatory patterns, which vary according to the stage of the sleep-waking cycle. Among these patterns, theta (4 – 12 Hz) and gamma (30 – 100 Hz) oscillations are prominent during active waking and REM sleep. However, the study of coupling patterns in the hippocampus has revealed distinct sub-types of oscillatory activity inside the traditional gamma band. Moreover, recent studies have shown the existence of even faster oscillations coupled to theta in the hippocampus (> 100 Hz), although there is a current divergence in the literature about whether they represent genuine network activity or spurious by-products from incomplete filtering of extracellular spikes. This thesis investigates oscillatory patterns generated by hippocampal neural networks, focusing in the coupling relation among oscillations of different frequencies. Using our own data and shared third-party ones of chronically implanted animals with multisite electrodes, we recorded electrical activity in the CA1 region of rats while exploring a familiar environment and during sleep stages. We investigated the existence of simultaneous but distinct oscillatory patterns in the hippocampus separated by electrophysiological, anatomic and behavioral markers, which, once taken together, can lead to a unique profile for each frequency band. Our results point to the existence of several frequency bands coupled to the hippocampal theta rhythm. All modulations are found to be separated by mechanisms that can potentially avoid interferences. We also demonstrate that a spurious oscillatory patterns can emerge and co-exist in the same frequency band of genuine oscillations and, contrary to recent work, we show that there is lack of evidence for n:m phase – phase coupling in the hippocampus. The capacity of neural oscillations to interact with one another raises questions about the biological significance of such phenomenon; despite recent progress in the field, however, its essence remains a mystery.