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A cage-based training, cognitive testing and enrichment system optimized for rhesus macaques in neuroscience research.

ABSTRACT: In neurophysiological studies with awake non-human primates (NHP), it is typically necessary to train the animals over a prolonged period of time on a behavioral paradigm before the actual data collection takes place. Rhesus monkeys (Macaca mulatta) are the most widely used primate animal models in system neuroscience. Inspired by existing joystick- or touch-screen-based systems designed for a variety of monkey species, we built and successfully employed a stand-alone cage-based training and testing system for rhesus monkeys (eXperimental Behavioral Intrument, XBI). The XBI is mobile and easy to handle by both experts and non-experts; animals can work with only minimal physical restraints, yet the ergonomic design successfully encourages stereotypical postures with a consistent positioning of the head relative to the screen. The XBI allows computer-controlled training of the monkeys with a large variety of behavioral tasks and reward protocols typically used in systems and cognitive neuroscience research.

SUBMITTER: Calapai A

PROVIDER: S-EPMC5352800 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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A cage-based training, cognitive testing and enrichment system optimized for rhesus macaques in neuroscience research.

Calapai A A Berger M M Niessing M M Heisig K K Brockhausen R R Treue S S Gail A A

Behavior research methods 20170201 1

In neurophysiological studies with awake non-human primates (NHP), it is typically necessary to train the animals over a prolonged period of time on a behavioral paradigm before the actual data collection takes place. Rhesus monkeys (Macaca mulatta) are the most widely used primate animal models in system neuroscience. Inspired by existing joystick- or touch-screen-based systems designed for a variety of monkey species, we built and successfully employed a stand-alone cage-based training and tes ...[more]

PMID: 26896242

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Project description:The common γ-chain cytokine interleukin-15 (IL-15) plays a significant role in regulating innate and adaptive lymphocyte homeostasis and can stimulate anti-tumor activity of leukocytes. We have previously shown that the circulating IL-15 in the plasma is the heterodimeric form (hetIL-15), produced upon co-expression of IL-15 and IL-15 Receptor alpha (IL-15Rα) polypeptides in the same cell, heterodimerization of the two chains and secretion. We investigated the pharmacokinetic and pharmacodynamic profile and toxicity of purified human hetIL-15 cytokine upon injection in rhesus macaques. We compared the effects of repeated hetIL-15 administration during a two-week dosing cycle, using different subcutaneous dosing schemata, i.e. fixed doses of 0.5, 5 and 50 µg/kg or a doubling step-dose scheme ranging from 2 to 64 µg/kg. Following a fixed-dose regimen, dose-dependent peak plasma IL-15 levels decreased significantly between the first and last injection. The trough plasma IL-15 levels measured at 48 h after injections were significantly higher after the first dose, compared to subsequent doses. In contrast, following the step-dose regimen, the systemic exposure increased by more than 1 log between the first injection given at 2 µg/kg and the last injection given at 64 µg/kg, and the trough levels were comparable after each injection. Blood lymphocyte cell count, proliferation, and plasma IL-18 levels peaked at day 8 when hetIL-15 was provided at fixed doses, and at the end of the cycle following a step-dose regimen, suggesting that sustained expansion of target cells requires increasing doses of cytokine. Macaques treated with a 50 µg/kg dose showed moderate and transient toxicity, including fever, signs of capillary leak syndrome and renal dysfunction. In contrast, these effects were mild or absent using the step-dose regimen. The results provide a new method of optimal administration of this homeostatic cytokine and may have applications for the delivery of other cytokines.

Dataset Information

A cage-based training, cognitive testing and enrichment system optimized for rhesus macaques in neuroscience research.

Publications

A cage-based training, cognitive testing and enrichment system optimized for rhesus macaques in neuroscience research.

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