Theta modulated dynamics in the hippocampus and its inputs during spatial navigation

Abstract

The hippocampus is crucial for spatial navigation and has been hypothesized to integrate sensory information and mnemonic cues about items and experiences within a spatial context to create memories. Area CA1 is the hippocampal output to the cortex and how networks in CA1 interact locally and with their input and output brain regions to create representations of space is an active field of research. Theta oscillations (5-10 Hz) are known to provide an efficient way of communication within networks by coordinating neural responses in temporal windows and are also crucial for the activity of grid cells and place cells. This dissertation focuses on how theta oscillations mediate spatial encoding in area CA1. It is an established notion that the CA1 transverse axis exhibits functional segregation following the topology of entorhinal inputs such that the proximal CA1 is more spatially-selective and theta modulated than distal CA1. However, proximal and distal CA1 show no significant difference in a complex environment with different texture cues. We find that theta mediated activation along the CA1 transverse axis to represent space is also comparable in this experimental paradigm. Theta phase modulated spiking dynamics, including theta phase precession, help maintain a temporal code of space. The inputs contributing to the accelerating dynamics of theta phase precession in place cells are explored using a simple circuit model. We show that inputs lacking spatial selectivity or theta modulation can alter the shape of theta phase precession to more biologically realistic dynamics. This dissertation also demonstrates successful recordings of local field potentials (LFPs) simultaneously from the olfactory bulb, lateral entorhinal cortex and the hippocampus using one-of-a-kind, custom built hyperdrive as rats forage in a cue-controlled environment. An experimental paradigm to test if the lateral entorhinal cortex performs theta-mediated relevance-based filtering of sensory information to the hippocampus during spatial navigation is discussed. Overall, this dissertation uses experimental and computational modelling approaches to extend existing knowledge on theta-mediated spatial representations in the hippocampus.