Susceptibility to induction of long-term depression is associated with impaired memory in aged Fischer 344 rats

Abstract

The current study employed aged and young male Fischer 344 rats to examine the relationship between long-term depression (LTD), age, and memory. Memory performance was measured on two tasks that are sensitive to hippocampal function; inhibitory avoidance and spatial discrimination on the Morris water maze. The slope of the extracellular excitatory postsynaptic field potential was recorded from CA3-CA1 synapses in hippocampal slices. Low frequency stimulation (LFS) induced a modest LTD only in aged animals under standard recording conditions. The decrease in synaptic transmission examined only in aged animals correlated with memory scores on the spatial task and LTD was not observed in aged animals with the highest memory scores. LTD induction was facilitated by increasing the Ca 2+ /Mg 2+ ratio of the recording medium or employing a paired-pulse stimulation paradigm. Age differences disappeared when LFS was delivered under conditions of elevated Ca 2+ /Mg 2+ in the recording medium. Using multiple induction episodes under conditions which facilitate LTD-induction, no age-related difference was observed in the maximum level of LTD. The results indicate that the increased susceptibility to LTD induction is associated with impaired memory and results from a shift in the induction process. The possible relationship between LTD and memory function is discussed.

Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology

“…lower stimulus frequencies or fewer stimulus pulses) (for review see 4,6,16 ). Also, some labs, including ours, have observed increased susceptibility to LTD induction in aged rats 2,[17][18][19] , while other groups have found no difference or reduced susceptibility in their aged animals. As discussed briefly below (see Discussion), subtle but critical differences in experimental protocol may account for these discrepancies.…”

Contributions of impaired hippocampal plasticity and neurodegeneration to age-related deficits in hormonal pulsatility

“…An age-related impairment of LTP at hippocampal CA1 synapses has been consistently reported, and similar LTP deficits may also occur at CA3 and dentate granule neuron synapses (Katsuki et al, 1990;McGahon et al, 1999). LTD induction is enhanced at CA1 synapses in old compared to young rats (Foster and Kumar, 2007), an alteration which would be expected to impair learning and memory ability. (Perturbed calcium release from the endoplasmic reticulum has been suggested to play a role in the enhanced LTD that occurs in hippocampal neurons during aging (Kumar and Foster, 2005).…”

Late enrichment maintains accurate recent and remote spatial memory only in aged rats that were unimpaired when middle aged

“…The present results also showed that the impaired performance of aged rats during the training phase was due to a pronounced short-term memory deficit (higher short-term memory index), but also to a long-term memory deficit (higher long-term memory index), as previously reported using within-and between-days performance improvement as measures of short-and long-term memory, respectively (Aitken and Meaney 1989;Shukitt-Hale et al 1998). However, age-related deficits in short-term (Lindner et al 1992;McQuail and Nicolle 2015) or long-term memory (Foster and Kumar 2007) have also been reported. Variations in study design (massed versus distributed training trials, and the presence or the absence of an interpolated probe during the training phase) might explain these discrepancies.…”