Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2002.Includes bibliographical references.While it is well established that the rodent hippocampus plays a crucial role in the formation and retrieval of spatial memories, the neural mechanisms underlying this process have not been completely characterized. In this thesis I have combined large-scale recordings from multiple single cells within the hippocampus of behaving rodents with pharmacological and genetic manipulations of hippocampal function in order to investigate how the cellular and network properties of the hippocampus contribute to memory storage and retrieval. In Part I of this thesis, extracellular recordings are used to monitor systematic changes in the cellular properties of hippocampal pyramidal cells in vivo. These studies demonstrate that the biophysical characteristics of CA1 pyramidal cells undergo both short term (activity-dependent) and long-term (experience-dependent) modulations during behavior. Short tem changes in the biophysical state of hippocampal pyramidal cells interact with changes in synaptic input to determine the probability with which CA1 pyramidal cells generate single spikes or bursts of action potentials and may play an important role in influencing where and when mechanisms of plasticity are engaged during behavior (Chapters: 3-4). Longer term changes include: 1) input specific reductions in amplitude attenuation - consistent with an increase in dendritic excitability (Chapter 4), 2) increases in the rate of spike repolarization (Chapter 5), 3) reductions in spike count variability within bursts (Chapter 5), and modulations in burst length both during behavior and sleep (Chapter5).(cont.) Together, these results provide novel insights into how changes in the intrinsic properties of hippocampal pyramidal cells are related to the process of memory formation. In Part II of this thesis, hippocampal recordings are used to characterize a novel genetically engineered mouse line in which NMDA receptors are specifically deleted from pyramidal cells within the CA3 region of the adult hippocampus (CA3-NR1 KO; Nakazawa et.al., 2001). Results indicate that while spatial information is relatively preserved within the hippocampus of CA3-NR1 mice, CA1 place cell activity within mutant animals is more sensitive to perturbations of the sensory environment relative to place cell activity in control animals. Together with behavioral data, these results provide the first direct evidence for CA3 NMDA receptor involvement in associative memory recall.by Michael C. Quirk.Ph.D.