Measures of anxiety, amygdala volumes, and hippocampal scopolamine phMRI response in elderly female rhesus macaques

Abstract

In nonhuman primates, anxiety levels are typically assessed by observing social hierarchies or behavior in an intruder task. As measures of anxiety might influence performance on a particular cognitive task, it is important to analyze these measures in the same room as used for the cognitive task. As we use a playroom for the spatial maze test, we classified elderly female rhesus macaques (Macaca mulatta) monkeys, as bold or reserved monkeys based on the time spent in specific areas of this room. Based on their exploratory behavior in the playroom, bold monkeys were defined as animals that spent 20% more time in the unprotected areas of the room than in the protected areas, whereas reserved monkeys spent a comparable amount of time in both areas. MRI analyses showed that reserved monkeys had a smaller amygdala compared to bold monkeys but there were no group differences in hippocampal volumes. In addition, the amount of time spent in the corners of the room was negatively correlated with the right and total amygdala size. Finally, reserved monkeys showed a lower phMRI response to the muscarinic receptor antagonist scopolamine compared to the bold monkeys. Thus, in elderly female nonhuman primates measures of anxiety are associated with structural amygdala differences and hippocampal muscarinic receptor function.

Association of microtubule associated protein-2, synaptophysin, and apolipoprotein E mRNA and protein levels with cognition and anxiety levels in aged female rhesus macaques

“…If a monkey did not show preference for one area of the room, the monkey was considered low anxiety. Based on their exploratory behavior in the playroom, 7 out of 16 monkeys were classified as low anxiety monkeys and 9 out of 16 monkeys were classified as high anxiety monkeys [11]. …”

“…Using a voxel based morphology (VBM) method, the size of the amygdala and hippocampus was assessed for each monkey, as described [11]. Monkeys were fasted the night before and the morning of the MRI experiments for the anesthesia.…”

“…Voxel based morphology (VBM) was assessed for each amygdala, right and left side, and hippocampus, right and left side, and PFC. MRI analyses revealed that reserved monkeys had smaller amygdala volumes than bold monkeys and the total time spent in safer corners was negatively correlated with the right amygdala and total amygdala size [11]. In contrast to the amygdala, the volumes of the right or left hippocampus and right or left PFC were not different in reserved and bold monkeys.…”

“…Neuron numbers is preserved in the hippocampus [4] and parahippocampal region [5] of aged rats with impairments in spatial learning and the dentate gyrus might be most vulnerable to aging [6]. However, neurobiological changes in the prefrontal cortex (PFC) and hippocampus, brain regions necessary for cognitive function, and the amygdala, which plays a role in the regulation of anxiety [7–9] and can affect hippocampus-dependent cognitive performance [10–13], might play a role in this loss of function [11]. The dendritic protein microtubule associated protein 2 (MAP-2), the presynaptic marker synaptophysin (SYN), and apolipoprotein E (APOE), a protein which plays role in lipid transport and metabolism and also affects synaptic activity, have integral roles in cognition [14–18].…”

“…Recently, we classified cognitive performance in nonhuman primates in a spatial maze as good spatial performers (GSP) or poor spatial performers (PSP) and behavioral performance of these animals in the same maze as bold or reserved [10, 11]. In this study, we performed quantitative real-time PCR (qRT-PCR) and western blot analyses using post-mortem tissue from these animals to determine whether MAP2 , SYN , and APOE mRNA and protein levels in the PFC, hippocampus, and amygdala are associated with the cognitive or anxiety classification.…”