Effects of Pregabalin and Environmental Familiarity upon Hippocampal Theta

Abstract

The hippocampal formation is heavily involved in two major functions; spatial cognition and anxiety. Septo-hippocampal theta (5-10 Hz) is a very prominent oscillation in rodents and is believed to be a physiological substrate that plays a major role in processing spatial cognition and anxiety. Hippocampal theta can be recorded from awake rodents during voluntary movement (often called Type 1 theta) and during alert immobility (called Type 2 theta). Hippocampal theta frequency changes have been implicated in anxiety, spatial cognition, and environmental novelty (Jeewajee et al, 2008b). Theta frequency increases broadly linearly with running speed, and a computational model (Burgess, 2008) has theorised that the slope of this relationship relates to type 1 theta and spatial cognition, while its y intercept (i.e. at 0cm/s) relates to type 2 theta and thus potentially variables such as arousal and anxiety. The model predicts that instantaneous theta frequency is the sum of these two dissociable components.
In the present thesis, I examined the effects the anxiolytic pregabalin has on intercept and slope of the running-speed-to-theta-frequency relationship in freely moving rats. I find that pregabalin reduces intercept, further generalising the observation in Wells et al. (2013), whereby two known anxiolytic drugs, and one putative anxiolytic drug, reduced theta intercept. Additionally, this study examined the effects of environmental familiarisation upon the slope component of the theta-frequency-to-speed relationship. The Burgess 2008 model predicts that theta slope is reduced in environmental novelty and increases as the environment becomes familiar. I observed that slope was indeed flatter in novelty and steeper in later exposures. In summary, consistent with the predictions of Burgess 2008 and Wells et al 2013, the anxiolytic pregabalin reduced theta intercept, while environmental familiarisation increased theta slope.