Arousal elevation drives the development of oscillatory vocal output

Adult behaviors, such as vocal production, often exhibit temporal regularity. In contrast, their immature forms are more irregular. We ask whether the coupling of motor behaviors with arousal changes give rise to temporal regularity and drive the transition from variable to regular motor output over the course of development. We used marmoset monkey vocal production to explore this putative influence of arousal on the nonlinear changes in their developing vocal output patterns. Based on a detailed analysis of vocal and arousal dynamics in marmosets, we put forth a general model incorporating arousal and auditory-feedback loops for spontaneous vocal production. Using this model, we show that a stable oscillation can emerge as the baseline arousal increases, predicting the transition from stochastic to periodic oscillations occurring in marmoset vocal development. We further provide a solution for how this model can explain vocal development as the joint consequence of energetic growth and social feedback. Together, our model offers a plausible mechanism for the development of arousal-mediated adaptive behavior.

NogoA-expressing astrocytes limit peripheral macrophage infiltration after ischemic brain injury in primates

Astrocytes play critical roles after brain injury, but their precise function is poorly defined. Utilizing single-nuclei transcriptomics to characterize astrocytes after ischemic stroke in the visual cortex of the marmoset monkey, we observed nearly complete segregation between stroke and control astrocyte clusters. Screening for the top 30 differentially expressed genes that might limit stroke recovery, we discovered that a majority of astrocytes expressed RTN4A/ NogoA, a neurite-outgrowth inhibitory protein previously only associated with oligodendrocytes. NogoA upregulation on reactive astrocytes post-stroke was significant in both the marmoset and human brain, whereas only a marginal change was observed in mice. We determined that NogoA mediated an anti-inflammatory response which likely contributes to limiting the infiltration of peripheral macrophages into the surviving parenchyma.

Diffusion MRI Anisotropy in the Cerebral Cortex is Determined by Unmyelinated Tissue Features

The diffusion of water molecules through the brain is constrained by tissue and cellular substructure, which imposes an anisotropy that can be measured through diffusion magnetic resonance imaging (dMRI). In the white matter, myelinated axons strongly shape diffusion anisotropy; however, in gray matter the determinants of dMRI signals remain poorly understood. Here we investigated the histological tissue properties underlying dMRI anisotropy and diffusivity in the cerebral cortex of the marmoset monkey. We acquired whole brain ex vivo dMRI data designed for high signal-to-noise at ultra-high (150μm) resolution. We compared the MRI to myelin- and Nissl-stained histological sections obtained from the scanned brain. We found that dMRI anisotropy corresponds most strongly not with cortical myelin content, but rather with the microscale anisotropy of tissue features, most notably those unmyelinated features highlighted by Nissl staining. The results suggest that dMRI anisotropy in gray matter derives from the organization of unmyelinated neurites, which are known to be affected by neurodegenerative diseases.

Medial prefrontal cortex (A32 and A25) projections in the common marmoset: a subcortical anterograde study

This study was aimed at establishing the subcorticals substrates of the cognitive and visceromotor circuits of the A32 and A25 cortices of the medial prefrontal cortex and their projections and interactions with subcortical complexes in the common marmoset monkey (Callithrix jacchus). The study was primarily restricted to the nuclei of the diencephalon and amygdala. The common marmoset is a neotropical primate of the new world, and the absence of telencephalic gyrus favors the mapping of neuronal fibers. The biotinylated dextran amine was employed as an anterograde tracer. There was an evident pattern of rostrocaudal distribution of fibers within the subcortical nuclei, with medial orientation. Considering this distribution, fibers originating from the A25 cortex were found to be more clustered in the diencephalon and amygdala than those originating in the A32 cortex. Most areas of the amygdala received fibers from both cortices. In the diencephalon, all regions received projections from the A32, while the A25 fibers were restricted to the thalamus, hypothalamus, and epithalamus at different densities. Precise deposits of neuronal tracers provided here may significantly contribute to expand our understanding of specific connectivity among the medial prefrontal cortex with limbic regions and diencephalic areas, key elements to the viscerocognitive process.

Womb to womb: Maternal litter size and birth weight but not adult characteristics predict early neonatal death of offspring in the common marmoset monkey

A singular focus on maternal health at the time of a pregnancy leaves much about perinatal mortality unexplained, especially when there is growing evidence for maternal early life effects. Further, lumping stillbirth and early neonatal death into a single category of perinatal mortality may obscure different causes and thus different avenues of screening and prevention. The common marmoset monkey (Callithrix jacchus), a litter-bearing nonhuman primate, is an ideal species in which to study the independent effects of a mother’s early life and adult phenotypes on pregnancy outcomes. We tested two hypotheses in 59 marmoset pregnancies at the Southwest National Primate Research Center and the Barshop Institute for Longevity and Aging Studies. We explored 1) whether pregnancy outcomes were predicted independently by maternal adult weight versus maternal litter size and birth weight, and 2) whether stillbirth and early neonatal death were differentially predicted by maternal variables. No maternal characteristics predicted stillbirth and no maternal adult characteristics predicted early neonatal death. In univariate Poisson models, triplet-born females had a significantly increased rate of early neonatal death (IRR[se] = 3.00[1.29], p = 0.011), while higher birth weight females had a decreased rate (IRR[se] = 0.89[0.05], p = 0.039). In multivariate Poisson models, maternal litter size remained an independent predictor, explaining 13% of the variance in early neonatal death. We found that the later in the first week those neonates died, the more weight they lost. Together these findings suggest that triplet-born and low birth weight females have distinct developmental trajectories underlying greater rates of infant loss, losses that we suggest may be attributable to developmental disruption of infant feeding and carrying. Our findings of early life contributions to adult pregnancy outcomes in the common marmoset disrupt mother-blaming narratives of pregnancy outcomes in humans. These narratives hold that the pregnant person is solely responsible for pregnancy outcomes and the health of their children, independent of socioecological factors, a moralistic framing that has shaped clinical pregnancy management. It is necessary to differentiate temporal trajectories and causes of perinatal loss and view them as embedded in external processes to develop screening, diagnostic, and treatment tools that consider the full arc of a mother’s lived experience, from womb to womb and beyond.

High plasticity in marmoset monkey vocal development from infancy to adulthood

The vocal behavior of human infants undergoes marked changes across their first year while becoming increasingly speech-like. Conversely, vocal development in nonhuman primates has been assumed to be largely predetermined and completed within the first postnatal months. Contradicting this assumption, we found a dichotomy between the development of call features and vocal sequences in marmoset monkeys, suggestive of a role for experience. While changes in call features were related to physical maturation, sequences of and transitions between calls remained flexible until adulthood. As in humans, marmoset vocal behavior developed in stages correlated with motor and social development stages. These findings are evidence for a prolonged phase of plasticity during marmoset vocal development, a crucial primate evolutionary preadaptation for the emergence of vocal learning and speech.

Functional organization of frontoparietal cortex in the marmoset investigated with awake resting-state fMRI

Frontoparietal networks contribute to complex cognitive functions in humans and macaques such as working memory, attention, task-switching, response suppression, grasping, reaching, and eye movement control. However, little is known about the organization of frontoparietal networks in the New World common marmoset monkey (Callithrix jacchus) which is now widely recognized as a powerful nonhuman primate experimental animal. In this study, we employed hierarchical clustering of interareal BOLD signals to investigate the hypothesis that the organization of the frontoparietal cortex in the marmoset follows the organizational principles of the macaque frontoparietal system. We found that the posterior part of the lateral frontal cortex (premotor regions) was functionally connected to the anterior parietal areas while more anterior frontal regions (frontal eye field (FEF)) were connected to more posterior parietal areas (the area around lateral intraparietal area (LIP)). These overarching patterns of inter-areal organization are consistent with a recent macaque study. These findings demonstrate parallel frontoparietal processing streams in marmosets and support the functional homologies of FEF-LIP and premotor-anterior parietal pathways between marmoset and macaque.