Plasticity, Hippocampal Place Cells, and Cognitive Maps
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abstract
Memory of even the briefest event can last a lifetime. Thus, learning and memory require neuronal mechanisms that allow rapid, yet persistent, changes to brain circuits. Hippocampal neuropsychology, synaptic and cellular electrophysiology, pharmacology, and molecular genetics converge and begin to reveal these mechanisms. Lesions of the hippocampus profoundly impair memory for recent events in humans and rodents. Circuits within the hippocampus are remarkably plastic, and this plasticity is mediated in part through changes in synaptic strength and revealed by long-term potentiation (LTP) and long-term depression (LTD). N-methyl D-aspartate (NMDA) receptors, a subtype of glutamate receptor, are crucial for inducing these plastic changes, and blocking these receptors reduces plasticity and impairs learning in tasks that require the hippocampus. Molecular genetic alterations that disrupt signaling mechanisms downstream of the NMDA receptor also prevent LTP induction and impair hippocampus-dependent learning. N-methyl D-aspartate receptor mechanisms have also been linked to information coding by hippocampal neurons. Hippocampal cells fire selectively in specific and restricted locations (place fields) as rodents move through open environments. Place fields form within minutes and persist for months. N-methyl D-aspartate receptor antagonists prevent the establishment of stable place fields. The same molecular genetic manipulations that interfere with hippocampal NMDA receptor function, prevent LTP induction, and impair spatial learning also disrupt the formation of stable hippocampal place fields. Finally, learning has been improved in mice with genetically modified NMDA receptors that enhance LTP induction. Thus, hippocampal cells "learn" to encode the salient features of experience through NMDA receptor-dependent synaptic plasticity mechanisms, and this rapid and persistent neuronal encoding is a crucial step toward the formation of long-term memory. Disruption of these plasticity mechanisms may underlie age-related memory deficits.
