The Effects Of Emotion And Sleep Alterations On Hippocampus-Dependent Memory Consolidation

The activity of hippocampal place cells is thought to generate the contextual representations in which episodic memories are embedded. However, new memories are susceptible to disruption until they undergo a process known as consolidation, becoming more permanent over time. This dissertation examines how changes in emotion and alterations in sleep patterns influence hippocampus-dependent memory consolidation. I first investigated the role of the dorsal and ventral hippocampus in predator odor fear learning by administering a histone deacetylase (HDAC) inhibitor into the dorsal or ventral hippocampus at different stages of contextual fear conditioning. Then, using long-term electrophysiological recordings of place cells in mice undergoing fear and extinction learning, I examined how changes in emotional valence affect spatial representations in the hippocampus. Last, I explored the effects of sleep deprivation on place cell activity in young and aged adult mice during the object-place recognition (OPR) task. I found that HDAC inhibition after context pre-exposure enhanced fear learning in the dorsal hippocampus but led to fear generalization in the ventral, suggesting that the dorsal hippocampus may encode the specific details of a context while the ventral encodes general aspects of the environment. Moreover, electrophysiological recordings in the dorsal hippocampus revealed that different place cells remapped preferentially at different stages of predator odor fear learning and extinction, suggesting that the extinction memory trace is a complex memory composed of old and new learning. Finally, sleep deprivation (SD) impaired learning in young adult animals but enhanced it in aged animals, possibly due to enhanced consolidation of NREM during recovery. Old SD animals and young control mice exhibited stability throughout the experiment in one set of cells, while another set remapped in response to the introduction of objects and again to the moved object. This suggests that successful performance of the OPR task requires animals to maintain a stable representation of the static environment while updating a representation of object locations. Young SD animals exhibited long-term stability in both types of cells, reflecting a failure to update object-place representations, but control old animals exhibited complete global remapping, suggesting that their impairment stems from a failure to consolidate spatial representations formed during training. Together, these data demonstrate that emotion and sleep exert clear influences on hippocampus-dependent memory consolidation.