Dissociating space to understand hippocampal function

Environments are comprised of multiple spaces, each being a subjective collection of relationships organized into a reference frame of mutually stable features. A rotating arena was used to dissociate the environment into a stationary “room frame” and a rotating “arena frame.” Inactivating one hippocampus with tetrodotoxin (TTX) specifically prevented the learning, the consolidation, and the recall of conditioned place avoidance memories when the relations between (but not within) the room and arena frames were disorganized by rotation. The inactivation did not prevent place avoidance learning when the frame dissociation was prevented by either not rotating the arena, by hiding the stationary room frame cues with darkness, or by hiding the rotating arena frame cues with shallow water. Extracellular unit recordings in anaesthetized rats indicate that the TTX inactivation of one hippocampus silenced it and caused a brief disinhibition in the other hippocampus. Hippocampal activity had returned to preinactivation levels by the time of training. We speculate that the disinhibition marks a physiological reorganization within the hippocampal network that specifically prevented the rat from organizing spatial information from the rotation-disorganized environment. The data indicate that the process of organizing information from disordered stimuli is very sensitive to hippocampal integrity.