Linear relationship between the maintenance of hippocampal long‐term potentiation and retention of an associative memory

Abstract

The hypothesis that the maintenance or decay of an associative memory trace after an extended retention interval is a function of the residual strength of the synapses originally strengthened during learning was examined in a classical conditioning paradigm in which high-frequency stimulation of a hippocampal input--the medial perforant path--served as a conditioned stimulus. Rats received perforant path stimulus-foot shock pairings while engaged in a previously acquired food-motivated lever-pressing task. Conditioned suppression of lever pressing was the behavioral measure of learning and retention of the association. Stimulus trains to the perforant path at an intensity above the threshold for eliciting a population spike induced long-term potentiation of synaptic transmission in the dentate gyrus. Synaptic potentials recorded extracellularly in the dentate gyrus were subsequently monitored for 31 days to examine quantitatively the decay of synaptic potentiation, a period after which retention of the learned association was assessed. All rats learned the association to a similar extent and displayed equivalent amounts of long-term potentiation by the end of conditioning. A slowly decaying function of synaptic potentiation was observed in remembering rats, i.e., rats with high retention performance after the 31-day learning-to-retention interval, while forgetting was associated with a rapid decay of long-term potentiation. Behavioral performance at the long-term memory test was linearly correlated with the amplitude of long-term potentiation maintained just prior to the retention test. The results favor the hypothesis that long-term associative memory depends, at least in part, on the maintenance of elevated synaptic strengths in the pathway activated during learning and suggest a role for the lasting component of long-term potentiation in the maintenance of memory.

Evidence That Long-Term Potentiation Occurs within Individual Hippocampal Synapses during Learning

“…Positive results were obtained and confirmed in other experiments of this type (Doyere and Laroche, 1992). A more recent paradigm used multiple electrodes to show that the relative magnitudes of field EPSPs recorded at several sites within hippocampus, and evoked by a single stimulation site, are modified by learning (Whitlock et al, 2006).…”

The MAPK/ERK Cascade Targets Both Elk-1 and cAMP Response Element-Binding Protein to Control Long-Term Potentiation-Dependent Gene Expression in the Dentate GyrusIn Vivo

“…This form of synaptic plasticity, known as long-term potentiation (LTP), is widely accepted as a candidate cellular mechanism for the storage of information (Bliss and Collingridge, 1993). In the hippocampus, a brain structure implicated in several forms of learning, LTP can last for many hours or as long as days or weeks (Barnes, 1979;Doyère and Laroche, 1992). The longer-lasting phases of LTP require the transcription of genes and the synthesis of proteins during a critical period (Otani et al, 1989;Nguyen et al, 1994;Frey and Morris, 1997).…”

β-Adrenergic Receptor Activation Facilitates Induction of a Protein Synthesis-Dependent Late Phase of Long-Term Potentiation

“…Some forms of L-LTP also require transcription (Nguyen et al, 1994). There is strong correlative evidence that L-LTP contributes to hippocampal consolidation of long-term memory (Doyere and Laroche, 1992;Bourtchouladze et al, 1994;Abel et al, 1997;Jones et al, 2001;Genoux et al, 2002).…”