Electrical manipulation of cortical and hippocampal dynamics during slow-wave states

Anastasia Greenberg
Oscillations are a fundamental principle of neural operation, organized into a hierarchy of frequency bands with the dominant rhythm alternating within and across behavioral states. During states of sleep and anesthesia, brain activity in forebrain regions displays two major distinct activity patterns: activated states of low voltage fast activity in the neocortex along with theta activity in the hippocampus, and deactivated states of synchronized slow-wave activity in both structures. The
more » ... ture event during such slowwave states is the large amplitude slow oscillation (~1 Hz, SO) which is cortically generated through transitions between highly active depolarized (UP, ON) states and hyperpolarized (DOWN, OFF) states of complete quiescence. The SO dynamically propagates across the cortex and reaches the hippocampus, making this rhythm attractive for mediating corticohippocampal interactions. It has been demonstrated that such interactions during the SO support the consolidation of declarative (hippocampal-mediated) memories in humans, and that directly manipulating the SO using rhythmic electrical stimulation at a similar frequency to the SO can affect both properties of the SO as well as subsequent memory. However, such evidence is currently lacking a mechanistic explanation for how rhythmic stimulation alters the dynamic properties of the SO, such as its propagation patterns, and how it supports cortico-hippocampal communication that would ultimately lead to the behavioral memory effects. The aim of my thesis was to address these issues using a urethane-anesthetized rat and mouse model and applying slowly alternating rhythmic electrical fields to the frontal portions of the cortex. In Chapter 2 I examine the influence of sinusoidal electrical stimulation on spontaneous SO propagation dynamics using a simple three-channel linear electrode array iv LFP activity, likely by way of a specific pathway from the entorhinal cortex to the hippocampus. Stimulation also boosted the occurrence of hippocampal ripples which are implicated in memory replay as well as cortical spindles which are likewise associated with cortical plasticity and learning. Following the cessation of stimulation, cortico-hippocampal coordination at the SO band was enhanced and the flow of information, as assessed using Granger causality, was biased in the hippocampo-cortical direction. Gamma activity between the cortex and hippocampus showed enhanced synchrony following stimulation, with the effect being restricted to the hippocampal pyramidal cell layer, the output layer of the hippocampus, suggesting further that information flow was occurring in the hippocampalcortical direction. These results show that rhythmic electrical field stimulation alters forebrain-wide SO dynamics. Changes in cortico-cortical, cortico-hippocampal and hippocampo-cortical interplay as a result of stimulation may all play important roles during sleep. Understanding the mechanisms that are at play during and following the administration of such stimulation can promote the development of targeted protocols for the enhancement and disruption of memory consolidation for use in experimental settings and eventually to affect clinical outcomes. v
doi:10.7939/r30z7125w fatcat:lqjfwu4ofraynb3wa4nhfgj63a