Adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain.

Crossing the blood-brain barrier in primates is a major obstacle for gene delivery to the brain. Adeno-associated viruses (AAVs) promise robust, non-invasive gene delivery from the bloodstream to the brain. However, unlike in rodents, few neurotropic AAVs efficiently cross the blood-brain barrier in non-human primates.

Intravenous functional gene transfer throughout the brain of non-human primates using AAV.

Adeno-associated viruses (AAVs) promise robust gene delivery to the brain through non-invasive, intravenous delivery. However, unlike in rodents, few neurotropic AAVs efficiently cross the blood-brain barrier in non-human primates (NHPs). Here we describe AAV.

The central extended amygdala guides survival-relevant tradeoffs: Implications for understanding common psychiatric disorders.

To thrive in challenging environments, individuals must pursue rewards while avoiding threats. Extensive studies in animals and humans have identified the central extended amygdala (EAc)-which includes the central nucleus of the amygdala (Ce) and bed nucleus of the stria terminalis (BST)-as a conserved substrate for defensive behavior. These studies suggest the EAc influences defensive responding and assembles fearful and anxious states.

Randomized controlled trial of early, small-volume formula supplementation among newborns: A study protocol.

Childhood undernutrition is a major health burden worldwide that increases childhood morbidity and mortality and causes impairment in infant growth and developmental delays that can persist into adulthood. The first weeks and months after birth are critical to the establishment of healthy growth and development during childhood. The World Health Organization recommends immediate and exclusive breastfeeding (EBF).

Declining neutrophil production despite increasing G-CSF levels is associated with chronic inflammation in elderly rhesus macaques.

Aging is characterized by a loss of bone marrow hematopoietic tissue, systemic chronic inflammation, and higher susceptibility to infectious and noninfectious diseases. We previously reported the tightly regulated kinetics and massive daily production of neutrophils during homeostasis in adult rhesus macaques aged 3 to 19 yr (equivalent to approximately 10 to 70 yr of age in humans). In the current study, we observed an earlier release of recently dividing neutrophils from bone marrow and greater in-group variability of neutrophil kinetics based on in vivo BrdU labeling in a group of older rhesus macaques of 20-26 yr of age.

Evidence in primates supporting the use of chemogenetics for the treatment of human refractory neuropsychiatric disorders.

Non-human primate (NHP) models are essential for developing and translating new treatments that target neural circuit dysfunction underlying human psychopathology. As a proof-of-concept for treating neuropsychiatric disorders, we used a NHP model of pathological anxiety to investigate the feasibility of decreasing anxiety by chemogenetically (DREADDs [designer receptors exclusively activated by designer drugs]) reducing amygdala neuronal activity. Intraoperative MRI surgery was used to infect dorsal amygdala neurons with AAV5-hSyn-HA-hM4Di in young rhesus monkeys.

U-net model for brain extraction: Trained on humans for transfer to non-human primates.

Brain extraction (a.k.a.

Impact of individual demographic and social factors on human-wildlife interactions: a comparative study of three macaque species.

Despite increasing conflict at human-wildlife interfaces, there exists little research on how the attributes and behavior of individual wild animals may influence human-wildlife interactions. Adopting a comparative approach, we examined the impact of animals' life-history and social attributes on interactions between humans and (peri)urban macaques in Asia. For 10 groups of rhesus, long-tailed, and bonnet macaques, we collected social behavior, spatial data, and human-interaction data for 11-20 months on pre-identified individuals.

Sharing voxelwise neuroimaging results from rhesus monkeys and other species with Neurovault.

Animal neuroimaging studies can provide unique insights into brain structure and function, and can be leveraged to bridge the gap between animal and human neuroscience. In part, this power comes from the ability to combine mechanistic interventions with brain-wide neuroimaging. Due to their phylogenetic proximity to humans, nonhuman primate neuroimaging holds particular promise.

The Future of Women in Psychological Science.

There has been extensive discussion about gender gaps in representation and career advancement in the sciences. However, psychological science itself has yet to be the focus of discussion or systematic review, despite our field's investment in questions of equity, status, well-being, gender bias, and gender disparities. In the present article, we consider 10 topics relevant for women's career advancement in psychological science.

The entorhinal cortex of the monkey: VI. Organization of projections from the hippocampus, subiculum, presubiculum, and parasubiculum.

The organization of projections from the macaque monkey hippocampus, subiculum, presubiculum, and parasubiculum to the entorhinal cortex was analyzed using anterograde and retrograde tracing techniques. Projections exclusively originate in the CA1 field of the hippocampus and in the subiculum, presubiculum, and parasubiculum. The CA1 and subicular projections terminate most densely in Layers V and VI of the entorhinal cortex, with sparser innervation of the deep portion of Layers III and II.

Dorsal Amygdala Neurotrophin-3 Decreases Anxious Temperament in Primates.

Background: An early-life anxious temperament (AT) is a risk factor for the development of anxiety, depression, and comorbid substance abuse. We validated a nonhuman primate model of early-life AT and identified the dorsal amygdala as a core component of AT's neural circuit. Here, we combine RNA sequencing, viral-vector gene manipulation, functional brain imaging, and behavioral phenotyping to uncover AT's molecular substrates.

Altered Uncinate Fasciculus Microstructure in Childhood Anxiety Disorders in Boys But Not Girls.

Objective: Anxiety disorders are common, can result in lifelong suffering, and frequently begin before adolescence. Evidence from adults suggests that altered prefrontal-limbic connectivity is a pathophysiological feature of anxiety disorders. More specifically, in adults with anxiety disorders, decreased fractional anisotropy (FA), a measure of white matter integrity, has been observed in the uncinate fasciculus, the major tract that connects limbic and prefrontal regions.

Effects of estrogen and aging on synaptic morphology and distribution of phosphorylated Tyr1472 NR2B in the female rat hippocampus.

Age and estrogens may impact the mobility of N-methyl-D-aspartate receptors (NMDARs) in hippocampal synapses. Here, we used serial section immunogold electron microscopy to examine whether phosphorylated tyrosine 1472 NR2B (pY1472), which is involved in the surface expression of NMDARs, is altered in the dorsal hippocampus of young (3-4 months old) and aged (∼24 months old) ovariectomized rats treated with 17β-estradiol or vehicle for 2 days. The number of gold particles labeling pY1472 was higher in presynaptic and postsynaptic compartments of aged rats with low estradiol (vehicle-treated) compared to other groups.

The effects of neonatal amygdala or hippocampus lesions on adult social behavior.

The present report details the final phase of a longitudinal evaluation of the social behavior in a cohort of adult rhesus monkeys that received bilateral neurotoxic lesions of the amygdala or hippocampus, or sham operations at 2 weeks of age. Results were compared to previous studies in which adult animals received amygdala lesions and were tested in a similar fashion. Social testing with four novel interaction partners occurred when the animals were between 7 and 8 years of age.

Evidence of convergent evolution in humans and macaques supports an adaptive role for copy number variation of the β-defensin-2 gene.

β-defensins are a family of important peptides of innate immunity, involved in host defense, immunomodulation, reproduction, and pigmentation. Genes encoding β-defensins show evidence of birth-and-death evolution, adaptation by amino acid sequence changes, and extensive copy number variation (CNV) within humans and other species. The role of CNV in the adaptation of β-defensins to new functions remains unclear, as does the adaptive role of CNV in general.

Abnormal infant islet morphology precedes insulin resistance in PCOS-like monkeys.

Polycystic ovary syndrome (PCOS) is prevalent in reproductive-aged women and confounded by metabolic morbidities, including insulin resistance and type 2 diabetes. Although the etiology of PCOS is undefined, contribution of prenatal androgen (PA) exposure has been proposed in a rhesus monkey model as premenopausal PA female adults have PCOS-like phenotypes in addition to insulin resistance and decreased glucose tolerance. PA female infants exhibit relative hyperinsulinemia, suggesting prenatal sequelae of androgen excess on glucose metabolism and an antecedent to future metabolic disease.

An analysis of entorhinal cortex projections to the dentate gyrus, hippocampus, and subiculum of the neonatal macaque monkey.

The entorhinal cortex is the primary interface between the hippocampal formation and neocortical sources of sensory information. Although much is known about the cells of origin, termination patterns, and topography of the entorhinal projections to other fields of the adult hippocampal formation, very little is known about the development of these pathways, particularly in the human or nonhuman primate. We have carried out experiments in which the anterograde tracers (3) H-amino acids, biotinylated dextran amine, and Phaseolus vulgaris leucoagglutinin were injected into the entorhinal cortex in 2-week-old rhesus monkeys (Macaca mulatta).

Degree of Chinese ancestry affects behavioral characteristics of infant rhesus macaques (Macaca mulatta).

Background: The use of Chinese-origin macaques in biomedical research is problematic for some scientists because of the reported behavioral and physiological differences from those of Indian origin. However, few studies have examined the effects of varying degrees of Chinese ancestry (DCA) on behavior, and they were typically based on small sample sizes and unusual rearing conditions.

Methods: Using data from a colony-wide program, we examined whether DCA was related to behavior and temperament ratings reflecting emotionality (fearfulness, aggression, and anxiety) and activity.

Intrinsic connections of the macaque monkey hippocampal formation: II. CA3 connections.

We examined the topographic organization of the connections of the CA3 field of the macaque monkey hippocampus. Discrete anterograde and retrograde tracer injections were made at various positions within CA3 and CA1. The projections from CA3 to CA1 (Schaffer collaterals), which terminate in the strata radiatum, pyramidale, and oriens, are present throughout the entire transverse extent of CA1.

Effects of neonatal amygdala or hippocampus lesions on resting brain metabolism in the macaque monkey: a microPET imaging study.

Longitudinal analysis of animals with neonatal brain lesions enables the evaluation of behavioral changes during multiple stages of development. Interpretation of such changes, however, carries the caveat that permanent neural injury also yields morphological and neurochemical reorganization elsewhere in the brain that may lead either to functional compensation or to exacerbation of behavioral alterations. We have measured the long-term effects of selective neonatal brain damage on resting cerebral glucose metabolism in nonhuman primates.

The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies).

The dentate gyrus is a simple cortical region that is an integral portion of the larger functional brain system called the hippocampal formation. In this review, the fundamental neuroanatomical organization of the dentate gyrus is described, including principal cell types and their connectivity, and a summary of the major extrinsic inputs of the dentate gyrus is provided. Together, this information provides essential information that can serve as an introduction to the dentate gyrus--a "dentate gyrus for dummies.

The distribution of serotonergic fibers in the macaque monkey amygdala: an immunohistochemical study using antisera to 5-hydroxytryptamine.

Though both the amygdala and the serotonin system appear to play critical roles in regulating fear and anxiety, little is known regarding the organization of serotonergic inputs to the primate amygdala. The present study employed immunohistochemistry to determine the distribution of serotonin fibers in the macaque amygdala. The brains of three adult male Macaca fascicularis monkeys were prepared for histological analysis using a polyclonal antibody to serotonin.