The Role of Hippocampal Brain Rhythms and Neural Spikes in Episodic Memory Processes

Information processing in the brain and the representation of episodic memories is supported by electrical activity in the hippocampus and related structures. Episodic memory, also known as autobiographical memory, stores the spatial, temporal and personal contexts of our past experiences and is often compromised in Alzheimer's disease and other types of amnesia. Although the mechanisms by which we encode and recall our experiences over time has been widely studied, the processes involved in successful learning or recall of cognitively demanding information has received much less attention. The understanding of such mechanisms is critical to the development of therapies or neural prosthetics for cognitive disorders. The present study was designed to address two specific questions related to these processes: 1) How does rhythmic activity in the hippocampus support encoding and retrieval of episodic memories and can such activity be manipulated to provide recovery of cognitive function in amnesia? 2) What is the role of hippocampal rhythmic and spiking activity in encoding and recall of episodic memory when the cognitive demand is high and potentially interfering information must be remembered?;Using a multi-level approach involving pharmacological, behavioral and electrophysiological manipulations, the first study explored the role of theta and gamma rhythmic coupling and patterned brain stimulation in episodic memory processes in rats. Episodic memory was tested using a one-trial learning spatial radial-arm water maze task where control and amnesic rats had to swim to a hidden platform at the end of one arm and return to that location on subsequent trials. Successful performance required animals to form a stable representation of the goal location on the first trial (encoding), and then remember that location from different start arms (retrieval). Single-trial spatial memory performance was predicted by the power comodulation of theta (4-10 Hz) and low gamma (30-50 Hz) rhythms in the hippocampus. Theta-gamma comodulation (TGC) was prominent during successful memory retrieval but was weak when memory failed or was unavailable during spatial exploration in sample trials. Muscimol infusion into medial septum (amnesic) reduced the probability of TGC and successful memory retrieval. In contrast, patterned electrical stimulation of the fimbria-fornix increased TGC in amnestic animals and partially rescued memory performance in the water maze. The results suggest that TGC accompanies memory retrieval in the hippocampus and that patterned brain stimulation may guide therapeutic strategies for the development of neural prostheses. Because all control animals performed at ceiling in this task, we were unable to evaluate the memory enhancing effects of fornix stimulation or the influence of TG comodulation above baseline. To further evaluate the dynamics of episodic encoding and retrieval in the context of high cognitive demand, we designed a second study using a proactive interference memory task.;In the second study, we recorded neural spikes and local field potentials from area CA1 while rats performed either a retrospective or prospective task with high cognitive demand on a six-arm radial maze. The tasks required animals to perform a series of trajectories to either a constant goal arm or from a constant start arm, respectively. After the addition of a novel trajectory, we evaluated the dynamic remapping of already established fields. Stably recorded cells exhibited a significant influence of spatial location, journey and task phase, suggesting the learning-dependent remapping in a familiar environment. We observed that representations of past locations or trajectories were dynamically grouped into stable or new representations. Further, representations of the novel trajectory often produced partial remapping that produced a three-way journey dependent code in the hippocampus.;These results demonstrate that the encoding and retrieval of spatial episodic memories in rats may be predicted by rhythmic oscillations in the hippocampus, and to an extent, controlled through brain stimulation. Further, the representation of already established memories is dynamically updated with new learning which reorganizes the hippocampal code. These studies suggest that real-time processing of information related to episodic encoding and retrieval is supported by rhythmic oscillations and spiking activity in the hippocampus which can be inform therapeutic strategies for cognitive dysfunction.