Abstract

Appetitive trace conditioning (TC) was examined over 6 months in younger-adult (2-8 months) and middle-aged (12-18 months) male Wistar RccHan rats, to test for early age-related impairment in working memory. Novel object recognition (NOR) was included as a comparison task, to provide a positive control in the event that the expected impairment in TC was not demonstrated. The results showed that TC improved at both ages at the 2 s but not at the 10 s trace interval. There was, however, evidence for reduced improvement from one day to the next in the middle-aged cohort tested with the 2 s trace conditioned stimulus. Moreover, within the 10 s trace, responding progressively distributed later in the trace interval, in the younger-adult but not the middle-aged cohort. Middle-aged rats showed NOR discriminative impairment at a 24 h but not at a 10 min retention interval. Object exploration was overall reduced in middle-aged rats and further reduced longitudinally. At the end of the study, assessing neurochemistry by HPLC-ED showed reduced 5-HIAA/5-HT in the dorsal striatum of the middle-aged rats and some correlations between striatal 5-HIAA/5-HT and activity parameters. Overall the results suggest that, taken in isolation, age-related impairments may be overcome by experience. This recovery in performance was seen despite the drop in activity levels in older animals, which might be expected to contribute to cognitive decline.

Highlights

  • The purpose of the study was to test for early age-related impairment in working memory in a behavioural model of aging

  • Even quite short temporal discontiguity can be sufficient to reduce associative learning. Such learning impairment has been related to the cognitive demands of the trace conditioning (TC) procedure: to associate ‘what goes with what’ when events are separated in time relies on working memory, defined as the capacity to maintain ‘on line’ transitory information (Gilmartin, Balderston, & Helmstetter, 2014; Goldman-Rakic, 1996; Sweatt, 2004)

  • The difference between the cohorts is of most importance because differences in ITI responding potentially confound the measure of TC provided by CS responding

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Summary

Introduction

The purpose of the study was to test for early age-related impairment in working memory in a behavioural model of aging. Trace conditioning (TC) procedures are used to test animals’ ability to associate events across a time interval, in this case between a conditioned stimulus (CS, e.g. noise) offset and an unconditioned stimulus (US, e.g. food or footshock) onset (Kamin, 1965). Even quite short temporal discontiguity can be sufficient to reduce associative learning. Such learning impairment has been related to the cognitive demands of the TC procedure: to associate ‘what goes with what’ when events are separated in time relies on working memory, defined as the capacity to maintain ‘on line’ transitory information (Gilmartin, Balderston, & Helmstetter, 2014; Goldman-Rakic, 1996; Sweatt, 2004). Earlier studies have shown that TC declines with normal aging in a number of species, including rabbits (Graves & Solomon, 1985), rats (McEchron, Cheng, & Gilmartin, 2004; Moyer & Brown, 2006), mice (Galvez, Cua, & Disterhoft, 2011; Kishimoto, Suzuki, Kawahara, & Kirino, 2001), and man

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