Plasticity, Hippocampal Place Cells, and Cognitive Maps

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.

Reversal of Memory Deficits by Atorvastatin and Simvastatin in Rats

“…Activation of NMDA receptors increase in‰ux of extracellular calcium in the neuronal cells, thereby increasing free intracellular calcium, which binds to calmodulin and subsequently stimulates relevant gene expression that eventually leads to enhancement of short term and long term memory. [48][49][50] Therefore, it may be possible that the observed ameliorative eŠect of statins on Alprazolam induced amnesia may be mediated through enhanced brain level of NO and through activation of NMDA receptors.…”

Cognitive Aging and the Hippocampus: How Old Rats Represent New Environments

“…Our observation that these manifestations of aging occur sequentially suggests a model of hippocampal aging that can be related to neurobiological changes in hippocampal circuitry during aging. Rigidity, delayed control by external cues, and multi-stability When moved from a familiar environment to a novel one, hippocampal neurons of young rats rapidly develop spatial representations that are unrelated to those of the familiar environment, and these representations are strongly under the control of salient visual landmarks (Wilson and McNaughton, 1993;Shapiro, 2001). Previous experiments have demonstrated that hippocampal cells of aged rats abnormally maintain existing spatial representations over multiple experiences despite alterations in environment or task demands sufficient to induce new representations in young rats during the first experience (Tanila et al, 1997b;Oler and Markus, 2000;Wilson et al, 2003).…”

Framingham Cardiovascular Risk Profile Correlates with Impaired Hippocampal and Cortical Vasoreactivity to Hypercapnia

“…Hippocampus is a major anatomical substrate of memory (Eichenbaum, 2004;Shapiro, 2001), and its structural and functional abnormalities predict Alzheimer's disease (AD) (Glodzik-Sobanska et al, 2005;Mosconi, 2005). As hippocampal cornu ammonis sector1 is highly sensitive to both AD pathology and ischemia (Zarow et al, 2005), the presence of vascular risk can strongly compound on AD-related damage.…”