An Integrative Approach to the Study of Cognitive Abilities in a Non-Human Primate Model in a Virology Laboratory Environment

Abstract

Non-human primates, due to their similarities in immune response to humans, are the preferred model for studying infectious processes and any associated cognitive impairments. Behavioral tests are indispensable for investigating pathogenesis in neuroinfections, especially those that do not manifest with noticeable clinical symptoms, as well as in the transition to a chronic form of the disease. Modeling viral infection requires specialized experimental conditions. Our work describes techniques for investigating mnemonic functions, tiredness, attentional focus, quick-wittedness, and basic behavioral responses in primates under the assumed conditions for infections with viruses that do not have an airborne route of transmission. It also outlines approaches to the training and selection of primates for virological research, as well as analyzing gender differences in learning abilities, the impact of housing conditions on the results, and the correlation between training success and behavioral test scores. These methods will allow a more detailed study of non-human primates as a model for researching cognitive and behavioral impairments under infectious and immune stress, as well as the design of less energy-intensive experiments for evaluating the efficacy and safety of therapeutic and prophylactic strategies at early stages of infection.

Keywords: behavior; cognitive function; cognitive tests; long-tailed macaques; non-human primates; positive reinforcement training; training techniques; virus infection.

Figure 1

Overall experimental design. Chronology of the experimental process and procedures.

Figure 2

The “Tool Use: Pulling Cloth with Treat” test.

Figure 3

The “Tool Properties: Whole and Cut Threads with a Treat” test.

Figure 4

The “Sticker Cup” test.

Figure 5

The “Box” test. Graphic design of the box and lock.

Figure 6

The “Reaction to a New Object” test.

Figure 7

Individual results with time for all primates during different periods of the 2-week training. The red line separates the functional primates (above 6 points) from the non-functional ones (below 6 points) for the second and third training periods. Saline had not yet been administered to Saline 1 and Saline 2 primates during the training period. The primates without manipulations were labeled Control 1–17.

Figure 8

The outcomes of the “Tool Use and Properties” test in relation to time during the final day of the training and on day 5 after the manipulations. Saline had not yet been administered to the Saline 1 and Saline 2 primates during the training period; homonymy was retained throughout for ease of reference. The primates without manipulations were labeled Control 1–17.

Figure 9

The results of the “Memory” test in relation to time during the final day of the training and on day 5 after the manipulations. Saline had not yet been administered to the Saline 1 and Saline 2 primates during the training period; homonymy was retained throughout for ease of reference. The primates without manipulations were labeled Control 1–17.

Figure 10

The results of the “Box” test in relation to time during the final day of the training and on day 5 after the manipulations. Saline had not yet been administered to the Saline 1 and Saline 2 primates during the training period; homonymy was retained throughout for ease of reference. The primates without manipulations were labeled Control 1–17.

Figure 11

The results of the latency characteristic evaluation in the test “Reaction to a New Object” in terms of dynamics before manipulations (training period results) and on day 3 after manipulations. Primates that were unsuccessful in the test and declined to engage with the experimenters or whose test completion time exceeded 100 s are situated above the red line. Saline had not yet been administered to the Saline 1 and Saline 2 primates during the training period; homonymy was retained throughout for ease of reference. The primates without manipulations were labeled Control 1–17.

Figure 12

The results of the activity characteristic evaluation from the test “Reaction to a New Object” in terms of dynamics before manipulations (A1 (training period results)) and on day 3 after manipulations (A4 and B1). Saline had not yet been administered to the Saline 1 and Saline 2 primates during the training period; homonymy was retained throughout for ease of reference. Primates without manipulations were labeled Control 1–17.

Figure 13

The results of the concentration characteristic evaluation in the test “Reaction to a New Object” in terms of dynamics before manipulations (A1 (training period results)) and on day 3 after manipulations (A4 and B1). Saline had not yet been administered to the Saline 1 and Saline 2 primates during the training period; homonymy was retained throughout for ease of reference. Primates without manipulations were labeled Control 1–17.

Figure 14

The results of the “Tiredness” test in terms of dynamics on the last day of training (final training results) and on day 5 after manipulations. Saline had not yet been administered to the Saline 1 and Saline 2 primates during the training period; homonymy was retained throughout for ease of reference. Primates without manipulations were labeled Control 1–17.

Figure 15

The influence of cage location on confidence in the experimenter and the research activity of primates. Floor 1: cage location at leg level; Floor 2: cage location at waist level; Floor 3: cage location at head level. Asterisks indicate statistically significant differences.