Genetically modified non-human primate models for research on neurodegenerative diseases

Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.

AB015.Interocular normalization in monkey primary visual cortex(V1)

Background:The two images,slightly different,seen by the two eyes allow the brain to build a 3D representation of the world.Monocular signals enter the primary visual cortex through layer 4,where they are segregated and organized in ocular dominance stripes.They are later combined in upper layers.In order to study the integration of the information coming from the two eyes at this mesoscopical scale in V1,we use optical imaging in anaesthetized macaque monkey.Methods:Ocular dominance maps have been obtained with intrinsic optical imaging.Dichoptic interactions have then been studied with voltage-sensitive dye imaging(VSDI)with a frequency-tagging paradigm.Visual stimuli with different contrasts were respectively presented at 6 and 10 Hz to the two eyes,independently or simultaneously with a passive 3D screen.Frequency analysis thus allowed to identify each eye’s contribution to the signal.Results:We observed that V1 population activity generated by one eye stimulation is suppressed when the other eye is stimulated too.This integration of monocular signals at the population level can be accurately modeled with an interocular normalization model.Conclusions:This approach and this model confirm V1 implication in combining the signals coming from the two eyes.The mechanisms underlying this interocular normalization,through local,feedforward,feedback or long-range connections,are still to be determined.