Optogenetics has revolutionized neuroscience in small laboratory animals, but its effect on animal models more closely related to humans, such as non-human primates (NHPs), has been mixed. To make evidence-based decisions in primate optogenetics, the scientific community would benefit from a centralized database listing all attempts, successful and unsuccessful, of using optogenetics in the primate brain. We contacted members of the community to ask for their contributions to an open science initiative. As of this writing, 45 laboratories around the world contributed more than 1,000 injection experiments, including precise details regarding their methods and outcomes. Of those entries, more than half had not been published. The resource is free for everyone to consult and contribute to on the Open Science Framework website. Here we review some of the insights from this initial release of the database and discuss methodological considerations to improve the success of optogenetic experiments in NHPs.An asterisk indicates two viral constructs mixed in the same solution. LT-HSV, long-term herpes simplex virus; AAV, adeno-associated virus; LVV, lentiviral vector; EIAV, equine infectious anemia
Eight standard inbred mouse strains were evaluated for ethanol effects on a refined battery of behavioral tests in a study that was originally designed to assess the influence of rat odors in the colony on mouse behaviors. As part of the design of the study, two experimenters conducted the tests, and the study was carefully balanced so that equal numbers of mice in all groups and times of day were tested by each experimenter. A defect in airflow in the facility compromised the odor manipulation, and in fact the different odor exposure groups did not differ in their behaviors. The two experimenters, however, obtained markedly different results for three of the tests. Certain of the experimenter effects arose from the way they judged behaviors that were not automated and had to be rated by the experimenter, such as slips on the balance beam. Others were not evident prior to ethanol injection but had a major influence after the injection. For several measures, the experimenter effects were notably different for different inbred strains. Methods to evaluate and reduce the impact of experimenter effects in future research are discussed.
The central mesencephalic reticular formation, a region associated with horizontal gaze control, has recently been shown to project to the supraoculomotor area in primates. The Edinger–Westphal nucleus is found within the supraoculomotor area. It has two functionally and anatomically distinct divisions: (1) the preganglionic division, which contains motoneurons that control both the actions of the ciliary muscle, which focuses the lens, and the sphincter pupillae muscle, which constricts the iris, and (2) the centrally projecting division, which contains peptidergic neurons that play a role in food and fluid intake, and in stress responses. In this study, we used neuroanatomical tracers in conjunction with immunohistochemistry in Macaca fascicularis monkeys to examine whether either of these Edinger–Westphal divisions receives synaptic input from the central mesencephalic reticular formation. Anterogradely labeled reticular axons were observed making numerous boutonal associations with the cholinergic, preganglionic motoneurons of the Edinger–Westphal nucleus. These associations were confirmed to be synaptic contacts through the use of confocal and electron microscopic analysis. The latter indicated that these terminals generally contained pleomorphic vesicles and displayed symmetric, synaptic densities. Examination of urocortin-1-positive cells in the same cases revealed fewer examples of unambiguous synaptic relationships, suggesting the centrally projecting Edinger–Westphal nucleus is not the primary target of the projection from the central mesencephalic reticular formation. We conclude from these data that the central mesencephalic reticular formation must play a here-to-for unexpected role in control of the near triad (vergence, lens accommodation and pupillary constriction), which is used to examine objects in near space.
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