RESUMEN
PURPOSE: The common marmoset (Callithrix jacchus) provides an ideal model to study early development of primates, and an in vivo platform to validate conclusions from in vitro studies of human embryos and embryo models. Currently, however, no established staging atlas of marmoset embryonic development exists. Using high-resolution, longitudinal ultrasound scans on live pregnant marmosets, we present the first dynamic in vivo imaging of entire primate gestation beginning with attachment until the last day before birth. METHODS: Our study unveils the first dynamic images of an in vivo attached mammalian embryo developing in utero, and the intricacies of the delayed development period unique to the common marmoset amongst primates, revealing a window for somatic interventions. RESULTS: Established obstetric and embryologic measurements for each scan were used comparatively with the standardized Carnegie staging of human development to highlight similarities and differences. Our study also allows for tracking the development of major organs. We focus on the ontogeny of the primate heart and brain. Finally, input ultrasound images were used to train deep neural networks to accurately determine the gestational age. All our ultrasounds and staging data recording are posted online so that the atlas can be used as a community resource toward monitoring and managing marmoset breeding colonies. CONCLUSION: The temporal and spatial resolution of ultrasound achieved in this study demonstrates the promise of noninvasive imaging in the marmoset for the in vivo study of primate-specific aspects of embryonic and fetal development.
Asunto(s)
Callithrix , Desarrollo Embrionario , Desarrollo Fetal , Ultrasonografía Prenatal , Callithrix/embriología , Animales , Femenino , Embarazo , Ultrasonografía Prenatal/métodos , Edad Gestacional , Humanos , Embrión de Mamíferos/diagnóstico por imagenRESUMEN
In the reach and saccade regions of the posterior parietal cortex (PPC), multiregional communication depends on the timing of neuronal activity with respect to beta-frequency (10-30 Hz) local field potential (LFP) activity, termed dual coherence. Neural coherence is believed to reflect neural excitability, whereby spiking tends to occur at a particular phase of LFP activity, but the mechanisms of multiregional dual coherence remain unknown. Here, we investigate dual coherence in the PPC of non-human primates performing eye-hand movements. We computationally model dual coherence in terms of multiregional neural excitability and show that one latent component, a multiregional mode, reflects shared excitability across distributed PPC populations. Analyzing the power in the multiregional mode with respect to different putative cell types reveals significant modulations with the spiking of putative pyramidal neurons and not inhibitory interneurons. These results suggest a specific role for pyramidal neurons in dual coherence supporting multiregional communication in PPC.
Asunto(s)
Neuronas , Lóbulo Parietal , Animales , Potenciales de Acción/fisiología , Lóbulo Parietal/fisiología , Neuronas/fisiología , Células Piramidales/fisiologíaRESUMEN
The accurate and complete assembly of both haplotype sequences of a diploid organism is essential to understanding the role of variation in genome functions, phenotypes and diseases1. Here, using a trio-binning approach, we present a high-quality, diploid reference genome, with both haplotypes assembled independently at the chromosome level, for the common marmoset (Callithrix jacchus), an primate model system that is widely used in biomedical research2,3. The full spectrum of heterozygosity between the two haplotypes involves 1.36% of the genome-much higher than the 0.13% indicated by the standard estimation based on single-nucleotide heterozygosity alone. The de novo mutation rate is 0.43 × 10-8 per site per generation, and the paternal inherited genome acquired twice as many mutations as the maternal. Our diploid assembly enabled us to discover a recent expansion of the sex-differentiation region and unique evolutionary changes in the marmoset Y chromosome. In addition, we identified many genes with signatures of positive selection that might have contributed to the evolution of Callithrix biological features. Brain-related genes were highly conserved between marmosets and humans, although several genes experienced lineage-specific copy number variations or diversifying selection, with implications for the use of marmosets as a model system.
Asunto(s)
Callithrix/genética , Diploidia , Evolución Molecular , Genoma/genética , Genómica/normas , Animales , Investigación Biomédica , Variaciones en el Número de Copia de ADN , Femenino , Mutación de Línea Germinal/genética , Haplotipos/genética , Heterocigoto , Humanos , Mutación INDEL/genética , Masculino , Estándares de Referencia , Selección Genética , Diferenciación Sexual/genética , Cromosoma Y/genéticaRESUMEN
Coherent neuronal dynamics play an important role in complex cognitive functions. Optogenetic stimulation promises to provide new ways to test the functional significance of coherent neural activity. However, the mechanisms by which optogenetic stimulation drives coherent dynamics remain unclear, especially in the nonhuman primate brain. Here, we perform computational modeling and experiments to study the mechanisms of optogenetic-stimulation-driven coherent neuronal dynamics in three male nonhuman primates. Neural responses arise from stimulation-evoked, temporally dynamic excitatory (E) and inhibitory (I) activity. Spiking activity is more likely to occur during E/I imbalances. Thus the relative difference in the driven E and I responses precisely controls spike timing by forming a brief time interval of increased spiking likelihood. Experimental results agree with parameter-dependent predictions from the computational models. These results demonstrate that optogenetic stimulation driven coherent neuronal dynamics are governed by the temporal properties of E/I activity. Transient imbalances in excitatory and inhibitory activity may provide a general mechanism for generating coherent neuronal dynamics without the need for an oscillatory generator.SIGNIFICANCE STATEMENT We examine how coherent neuronal dynamics arise from optogenetic stimulation in the primate brain. Using computational models and experiments, we demonstrate that coherent spiking and local field potential activity is generated by stimulation-evoked responses of excitatory and inhibitory activity in networks, extending the growing literature on neuronal dynamics. These responses create brief time intervals of increased spiking tendency and are consistent with previous observations in the literature that balanced excitation and inhibition controls spike timing, suggesting that optogenetic-stimulation-driven coherence may arise from intrinsic E/I balance. Most importantly, our results are obtained in nonhuman primates and thus will play a leading role in driving the use of causal manipulations with optogenetic tools to study higher cognitive functions in the primate brain.
Asunto(s)
Encéfalo/fisiología , Simulación por Computador , Modelos Neurológicos , Neuronas/fisiología , Optogenética/métodos , Potenciales de Acción/fisiología , Animales , Macaca , MasculinoRESUMEN
Selecting and planning actions recruits neurons across many areas of the brain, but how ensembles of neurons work together to make decisions is unknown. Temporally coherent neural activity may provide a mechanism by which neurons coordinate their activity to make decisions. If so, neurons that are part of coherent ensembles may predict movement choices before other ensembles of neurons. We recorded neuronal activity in the lateral and medial banks of the intraparietal sulcus (IPS) of the posterior parietal cortex while monkeys made choices about where to look and reach. We decoded the activity to predict the choices. Ensembles of neurons that displayed coherent patterns of spiking activity extending across the IPS--'dual-coherent' ensembles--predicted movement choices substantially earlier than other neuronal ensembles. We propose that dual-coherent spike timing reflects interactions between groups of neurons that are important to decisions.