Long-term enhancement of hippocampal synaptic transmission and the acquisition of spatial information

Abstract

The hypothesis that memories are stored as a specific distribution of strengths in a population of modifiable synapses was examined by the bilateral induction of long-term enhancement in synapses of the main afferent fiber system to the hippocampal formation in rats. Brief, high-frequency activation of the perforant pathway in chronically prepared animals resulted in a persistent increase in the field EPSP and population spike, measured extracellularly in fascia dentata. This treatment resulted in a profound and persistent deficit in the acquisition of new spatial information in a task requiring spatial "reference" memory, and disruption of recently acquired spatial information. Well-established spatial memory was completely unaffected, however, as was the acquisition of spatial information into shortterm "working" memory. These results support the hypothesis that, during the formation of "cognitive maps," spatial information must be temporarily stored at modifiable synapses at the input stage to the hippocampal formation, but that this information is not needed once the representation of the environment is well established. Spatial working memory, in a familiar environment, appears not to depend on the distribution of synaptic strengths in this system at all.Most attempts to explain associative learning in the nervous system have invoked long-term changes in the efficacy of cellto-cell communication as the underlying information-storage medium (e.g., Hebb, 1949; Marr, 197 1). The common element of these theories is the assumption that information is stored as a specific distribution of modifiable synaptic weighting functions. These hypotheses predict that a treatment that disrupts such a distribution, by driving the population of modifiable synapses to the maximum strength, will disrupt the information content. This would have two consequences: impaired performance of tasks requiring the integrity of previously stored information, and impaired acquisition of new information. The present experiments were designed to examine this prediction by studying the effects on spatial learning and memory of artificially induced enhancement of synaptic efficacy in a large population of hippocampal synapses.Bliss, Lomo, and Gardner-Medwin first documented that brief episodes of electrical stimulation of perforant path fibers at physiological frequencies resulted in a lasting increase in synaptic transmission to hippocampal target neurons (Bliss and GardnerMedwin, 1973;Bliss and Lomo, 1973). Since this discovery, considerable evidence has accumulated in support of the hypothesis that this experimentally induced phenomenon represents the activation of a physiological process that normally Received Apr. 5, 1985; revised July 15, 1985; accepted July 17, 1985. This work was supported by PHS Grants AGO3376 and NS20331. We thank Seth Sharpless for help with computer software, B. Peterson for secretarial assistance, and P. Sharp and B. Jones Leonard for helpful comments on the manuscript. Lomo (1966) and the term LTP (long-term p...

Simultaneous training on two hippocampus-dependent tasks facilitates acquisition of trace eyeblink conditioning

“…LTP induction has also been shown to have effects on spatial learning. Several groups have shown that when the perforant pathdentate synapses are saturated, subsequent spatial learning is impaired (McNaughton et al 1986;Castro et al 1989;Barnes et al 1994;Moser et al 1998). Barnes et al (1994) have shown that there is a correlation between the amount of LTP induced at these synapses and learning ability.…”

Involvement of the CA3–CA1 Synapse in the Acquisition of Associative Learning in Behaving Mice

“…Indeed, it has been shown that spatial learning is prevented when saturating LTP is evoked in the perforant pathway or when evoked by the repeated stimulation of a large number of hippocampal synaptic contacts (McNaughton et al, 1986;Casto et al, 1989;Moser et al, 1998;Dragoi et al, 2003). The effects of LTP evoked at the hippocampus are more evident for the acquisition of new learning skills and on recently acquired knowledge, but not for remote memory retrieval (Morris et al, 2003).…”

Stimulation on the Positive Phase of Hippocampal Theta Rhythm Induces Long-Term Potentiation That Can Be Depotentiated by Stimulation on the Negative Phase in Area CA1In Vivo

“…Long-term potentiation (LTP) of neuronal synaptic responses has been discussed for 30 years as a possible model for synaptic changes that occur during learning (Lømo, 1966;Bliss and Lømo, 1973;McNaughton et al, 1986;Morris, 1989;Bliss and Collingridge, 1993). The standard protocol used by most researchers to induce LTP is high-frequency stimulation (HFS) in which several hundred pulses at frequencies of 100 -400 Hz are given to induce LTP.…”