Circadian activity associated with spatial learning and memory in aging rhesus monkeys

Abstract

In rodents, spatial learning and memory tests require navigation, whereas in nonhuman primates these tests generally do not involve a navigational component, thus assessing nonhomologous neural systems. To allow closer parallels between rodent and primate studies, we developed a navigational spatial learning and memory task for nonhuman primates and assessed the performance of elderly (19-25 years) female rhesus monkeys (Macaca mulatta). The animals were allowed to navigate in a room containing a series of food ports. After they learned to retrieve food from the ports, a single port was repeatedly baited and the animals were tested until they learned the correct location. The location of the baited port was then changed (shift position). We also determined whether test performance was associated with circadian activity measured with accelerometers. Performance measures included trials to criterion, search strategies, and several indices of circadian activity. Animals learned the task as reflected in their search strategies. Correlations were found between the number of initial or shift trials and circadian activity parameters including day activity, dark:light activity ratio, sleep latency, and wake bouts. Thus, disruptions in circadian rhythms in nonhuman primates are associated with poorer performance on this novel test. These data support the usefulness of this spatial navigational test to assess spatial learning and memory in rhesus monkeys and the importance of circadian activity in performance.

Role of Circadian Neuroendocrine Rhythms in the Control of Behavior and Physiology

“…An example of this self-sustained rhythmicity is illustrated in figure 1. The motor activity data depicted in figure 1a were obtained from an adult rhesus macaque using an Actiwatch, and emphasize the highly entrained diurnal pattern of activity that occurs under fixed 12L:12D photoperiods [33,34,35,36]. In addition, the data show how the activity rhythm becomes free-running, with slight phase advancement, when the animal is exposed to continuous dim illumination (30 lx).…”

Synchrony and desynchrony in circadian clocks: impacts on learning and memory

“…Prolonged circadian desynchronization can lead to increased mortality in aged animals (Davidson et al 2006). Age-associated alterations in circadian rhythms also impact memory and performance in animal models (Haley et al 2009;Kondratova et al 2010;Nakamura et al 2011), while in older individuals, fragmentation of rest-activity cycles is correlated with cognitive decline in mental speed, memory, and executive function (Oosterman et al 2009). The interaction between circadian rhythms and cognitive function in aged individuals represents an area of escalating concern given the rising age of modern societies.…”

Spatial Learning and Memory in Animal Models and Humans

“…In this test, the animals are placed in an open room containing food ports mounted to the wall. Nonhuman primates are trained to retrieve a food reward from a single baited port (33). Recently, we reported that during the first half of the trials, old female rhesus macaques mostly use a serial search pattern to find the baited port.…”