Because of its close phylogenetic relationship to the human, the non-human primate (NHP) brain holds enormous potential for understanding structure, function, development and pathology of the human brain. However, many obstacles impede studies of NHPs, among these, significant logistic, ethical, and financial burdens. The Department of Neuroscience at Yale houses a unique collection of brain tissue from NHP macaques, ranging in age from embryonic to adult, which was generated over four decades, in the laboratories of Dr. Pasko Rakic and the late Dr. Patricia Goldman-Rakic. The collection includes four Case Sets of slides: (1) [3H]thymidine-labeled serially cut brains for cell birth dating, (2) brains labeled with tritiated amino acids for tract tracing, (3) brains from monkeys with enucleations and selected cortical lesions, (4) and brains from prenatally X-irradiated and ultrasound-exposed monkeys sacrificed postnatally. A 5th Case Set is comprised of EM blocks from multiple brain regions of fetal and postnatal monkeys. The objective of this grant is to make this unique collection an international research resource (MacBrainResource) that is readily available to the neuroscience community at-large. To accomplish this, we propose (1) to inventory and catalogue the collection, (2) to restore the slides to optimal condition by re-coverslipping and in some instances re-staining them, (3) to publicize the resource via mailings, presentations at the Society for Neuroscience meetings and our website (MacBrainResource.org), and (4) to facilitate use of MacBrainResource by outside investigators both on site and remotely by transmission of high resolution images via the internet. The value of the MacBrainResource collection is immeasurable. Primate brain research not only requires animal sacrifice but is very expensive. Making existing NHP brain tissue available will avoid costly duplication of experiments and unnecessary sacrifice of animals. With increasing pressure to find alternatives to primate research, establishment of the MacBrainResource would allow researchers worldwide to conduct primate studies without the need to sacrifice a single new animal. Proof that this resource represents a viable and valuable alternative for de novo primate research comes from the publication of several recent papers that utilized this material (e.g. Duque at al., 2011; 2015; 2016; Ratnanather et al. 2013; Selemon et al., 2013) as well as demand for material from investigators all over that world. Dedicated personnel, proper cataloguing, and adequate equipment would ensure that these slides and EM blocks are preserved for future generations of neuroscientists to exploit, perhaps using methods not yet developed.

Public Health Relevance

A non-human primate (macaque) brain resource (MacBrainResource) will be established from slides and EM blocks generated in the laboratories of Drs. Pasko Rakic and Patricia Goldman-Rakic. This resource will enable neuroscientists worldwide to conduct de novo analyses of the macaque brain at a minimum cost to them and without having to sacrifice a single additional animal. Establishment of the MacBrainResource would honor our commitment as scientists to data and resource sharing and to establishing viable alternatives to animal research.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH113257-02
Application #
9429127
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Freund, Michelle
Project Start
2017-02-15
Project End
2021-12-31
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Yale University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520