Acquisition and baseline performance of working memory tasks by adolescent rhesus monkeys

Abstract

Adolescence is a transitional stage of development characterized by protracted refinements in the neural circuits required for adult level proficiency of working memory. Because impaired working memory is a hallmark feature of several psychiatric disorders that have their onset during adolescence, model systems that can be used to assess the maturation of working memory function, and of disease-related risk factors that disrupt its development, are of particular importance. However, few studies have investigated the maturation of working memory in nonhuman primates. Thus in the present study, we adapted two working memory tests that are among the most widely used in human and adult nonhuman primates, for adolescent rhesus monkeys. Using a touch-screen apparatus, monkeys were trained on a spatial delayed-response task to assess spatial working memory and a delayed match-to-sample task to assess object working memory. The results indicate that adolescent rhesus monkeys readily and efficiently acquire the ability to perform touch-screen based, complex tests of working memory. These data establish that distinct components of adult prefrontal cortex-dependent cognitive functions can be effectively modeled and evaluated in adolescent monkeys. As such, this approach should be useful for assessing the influence of environmental risk factors on the protracted maturation of working memory in adolescent macaques.

Monkeys rely on recency of stimulus repetition when solving short-term memory tasks

“…Measurements of behavioral performance in nonspatial delayed-match-to-sample tasks have been interpreted as showing that monkeys remember the sample using working memory, that is, they use selective memorization (Miller and Desimone 1994;Amit et al 2003;Schneider et al 2009;Verrico et al 2011). However, this interpretation has been made even when the delayed-match-to-sample task does not include intervening distractors (Schneider et al 2009;Verrico et al 2011), which are critical for distinguishing selective memorization from the neighborhood strategy.…”

“…The prototypical assay of nonspatial short-term memory in monkeys has been delayed-match-to-sample (Miller et al 1996;Amit et al 2003;Schneider et al 2009;Verrico et al 2011). In delayed-match-tosample, two or more stimuli are presented sequentially, separated by delays, and subjects report whether a test stimulus matches one of the sample stimuli.…”

Delay- and Dose-Dependent Effects of Δ9-Tetrahydrocannabinol Administration on Spatial and Object Working Memory Tasks in Adolescent Rhesus Monkeys

“…Housing and experimental procedures were conducted in accordance with United States Department of Agriculture and National Institutes of Health guidelines and with approval of the University of Pittsburgh's Institutional Animal Care and Use Committee. At 23.9 ± 0.6 months of age, animals were trained to respond to computerized touch-screens as previously described (Verrico et al, 2011). See Supplementary Materials and Methods for details.…”

“…At an average age of 27.6±1.1 months (range 26.4-30.0 months) and before the THC/vehicle administration, monkeys completed 4-5 weeks of baseline training on the SDR and DMTS tasks as previously described (Verrico et al, 2011). Importantly, monkeys performed both tasks in two sessions per day, spaced 30 min apart, B5 days per week.…”

“…The animals used in this study will also be included in a longitudinal study exploring the effects of long-term THC administration on age-related improvement in WM ability, thus the animals had only 4-5 weeks of baseline training before THC/vehicle administration (Verrico et al, 2011). This approach ensured that (1) the monkeys understood how to perform the tasks, (2) performance accuracy increased in a delay-dependent manner from the first to last week of baseline training, and (3) performance accuracy was well below ceiling levels.…”