Gastric emphysema and pneumatosis intestinalis in two common marmosets with duodenal dilation syndrome.

BACKGROUND: Common marmosets (Callithrix jacchus) are widely used as primate experimental models in biomedical research. Duodenal dilation with chronic vomiting in captive common marmosets is a recently described life-threatening syndrome that is problematic for health control. However, the pathogenesis and cause of death are not fully understood. CASE PRESENTATION: We report two novel necropsy cases in which captive common marmosets were histopathologically diagnosed with gastric emphysema (GE) and pneumatosis intestinalis (PI). Marmoset duodenal dilation syndrome was confirmed in each case by clinical observation of chronic vomiting and by gross necropsy findings showing a dilated, gas-filled and fluid-filled descending duodenum that adhered to the ascending colon. A diagnosis of GE and PI was made on the basis of the bubble-like morphology of the gastric and intestinal mucosa, with histological examination revealing numerous vacuoles diffused throughout the lamina propria mucosae and submucosa. Immunostaining for prospero homeobox 1 and CD31 distinguished gas cysts from blood and lymph vessels. The presence of hepatic portal venous gas in case 1 and possible secondary bacteremia-related septic shock in case 2 were suggested to be acute life-threatening abdominal processes resulting from gastric emphysema and pneumatosis intestinalis. CONCLUSIONS: In both cases, the gross and histopathological findings of gas cysts in the GI tract walls matched the features of human GE and PI. These findings contribute to clarifying the cause of death in captive marmosets that have died of gastrointestinal diseases.

Effects of enhanced insect feeding on the faecal microbiota and transcriptome of a family of captive common marmosets (Callithrix jacchus).

Common marmosets have been widely used in biomedical research for years. Nutritional control is an important factor in managing their health, and insect intake would be beneficial for that purpose because common marmosets frequently feed on insects in natural habitats. Here, we examined the effect of enhanced insect feeding on the gut by analysing the faecal microbiota and transcripts of captive marmosets. A family consisting of six marmosets was divided into two groups. During the seven-day intervention period, one group (the insect feeding group, or Group IF) was fed one cricket and one giant mealworm per marmoset per day, while the other (the control group, or Group C) was not fed these insects. RNA was extracted from faecal samples to evaluate the ecology and transcripts of the microbiota, which were then compared among time points before (Pre), immediately after (Post), and two weeks after the intervention (Follow_up) using total RNA sequencing. The gut microbiota of marmosets showed Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria as dominant phyla. Linear discriminant analysis showed differential characteristics of microbiota with and without insect feeding treatment. Further analysis of differentially expressed genes revealed increases and decreases in Bacteroidetes and Firmicutes, respectively, corresponding to the availability of insects under both Post and Follow_up conditions. Significant changes specific to insect feeding were also detected within the transcriptome, some of which were synchronized with the fluctuations in the microbiota, suggesting a functional correlation or interaction between the two. The rapid changes in the microbiota and transcripts may be achieved by the microbiota community originally developed in the wild through marmosets' feeding ecology. The results were informative for identifying the physiological impact of insect feeding to produce a better food regimen and for detecting transcripts that are currently unidentifiable.

Earliest evidence of primate captivity and translocation supports gift diplomacy between Teotihuacan and the Maya.

A multimethod archaeometry study (zooarchaeological, isotopic, ancient DNA, paleobotanical, and radiocarbon dating) of a spider monkey sacrificed in the ceremonial center of Teotihuacan, Mexico (1 to 550 CE) is interpreted as a diplomatic gift exchange with neighboring Maya. Not only does this spider monkey provide the earliest known instance of primate translocation and captivity in Mesoamerica, it helps date incipient modes of interregional diplomacy between two major powers during Early Classic Mesoamerica: Teotihuacan and the Maya. Details of human-primate interaction include age at capture and transport (before ∼3 y of age), captive duration (over 2 y), anthropogenic diet (staple was maize, though secondary resources unique to anthropogenic diet including arrowroot and chili pepper were also found), context of sacrifice (tethered and associated with complete golden eagle and an array of other statecrafts), and general site context (including presence of Maya vessels and Maya-style murals). The timing of the spider monkey's sacrifice (250 to 300 CE) and its life history suggest a reconsideration of epigraphically attested militaristic involvement of Teotihuacan at certain Maya sites. We propose that a period of more multilateral and fluid ritual exchange with Maya dignitaries preceded the Teotihuacan state's eventual ascent to prominence.

"Natural Laboratory Complex" for novel primate neuroscience.

We propose novel strategies for primate experimentation that are ethically valuable and pragmatically useful for cognitive neuroscience and neuropsychiatric research. Specifically, we propose Natural Laboratory Complex or Natural Labs, which are a combination of indoor-outdoor structures for studying free moving and socially housed primates in natural or naturalistic environment. We contend that Natural Labs are pivotal to improve primate welfare, and at the same time to implement longitudinal and socio-ecological studies of primate brain and behavior. Currently emerging advanced technologies and social systems (including recent COVID-19 induced "remote" infrastructures) can speed-up cognitive neuroscience approaches in freely behaving animals. Experimental approaches in natural(istic) settings are not in competition with conventional approaches of laboratory investigations, and could establish several benefits at the ethical, experimental, and economic levels.

Neurons of rat motor cortex become active during both grasping execution and grasping observation.

In non-human primates, a subset of frontoparietal neurons (mirror neurons) respond both when an individual executes an action and when it observes another individual performing a similar action.1-8 Mirror neurons constitute an observation and execution matching system likely involved in others' actions processing3,5,9 and in a large set of complex cognitive functions.10,11 Here, we show that the forelimb motor cortex of rats contains neurons presenting mirror properties analogous to those observed in macaques. We provide this evidence by event-related potentials acquired by microelectrocorticography and intracortical single-neuron activity, recorded from the same cortical region during grasping execution and observation. Mirror responses are highly specific, because grasping-related neurons do not respond to the observation of either grooming actions or graspable food alone. These results demonstrate that mirror neurons are present already in species phylogenetically distant from primates, suggesting for them a fundamental, albeit basic, role not necessarily related to higher cognitive functions. Moreover, because murine models have long been valued for their superior experimental accessibility and rapid life cycle, the present finding opens an avenue to new empirical studies tackling questions such as the innate or acquired origin of sensorimotor representations and the effects of social and environmental deprivation on sensorimotor development and recovery.

Neural Evidence of Mirror Self-Recognition in the Secondary Somatosensory Cortex of Macaque: Observations from a Single-Cell Recording Experiment and Implications for Consciousness.

Despite mirror self-recognition being regarded as a classical indication of self-awareness, little is known about its neural underpinnings. An increasing body of evidence pointing to a role of multimodal somatosensory neurons in self-recognition guided our investigation toward the secondary somatosensory cortex (SII), as we observed single-neuron activity from a macaque monkey sitting in front of a mirror. The monkey was previously habituated to the mirror, successfully acquiring the ability of mirror self-recognition. While the monkey underwent visual and somatosensory stimulation, multimodal visual and somatosensory activity was detected in the SII, with neurons found to respond to stimuli seen through the mirror. Responses were also modulated by self-related or non-self-related stimuli. These observations corroborate that vision is an important aspect of SII activity, with electrophysiological evidence of mirror self-recognition at the neuronal level, even when such an ability is not innate. We also show that the SII may be involved in distinguishing self and non-self. Together, these results point to the involvement of the SII in the establishment of bodily self-consciousness.

A novel mind-set in primate experimentation: Implications for primate welfare.

We emphasize the importance of studying the primate brain in cognitive neuroscience and suggest a new mind-set in primate experimentation within the boundaries of animal welfare regulations. Specifically, we list the advantages of investigating both genes and neural mechanisms and processes in the emergence of behavioral and cognitive functions, and propose the establishment of an open field of primate research. The latter may be conducted by implementing and harmonizing experimental practices with ethical guidelines that regulate (1) management of natural parks with free-moving populations of target nonhuman primates, (2) establishment of indoor-outdoor labs for both system genetics and neuroscience investigations, and (3) hotel space and technologies which remotely collect and dislocate information regarding primates geographically located elsewhere.

Spectral Power in Marmoset Frontal Motor Cortex during Natural Locomotor Behavior.

During primate arboreal locomotion, substrate orientation modifies body axis orientation and biomechanical contribution of fore- and hindlimbs. To characterize the role of cortical oscillations in integrating these locomotor demands, we recorded electrocorticographic activity from left dorsal premotor, primary motor, and supplementary motor cortices of three common marmosets moving across a branch-like small-diameter pole, fixed horizontally or vertically. Animals displayed behavioral adjustments to the task, namely, the horizontal condition mainly induced quadrupedal walk with pronated/neutral forelimb postures, whereas the vertical condition induced walk and bound gaits with supinated/neutral postures. Examination of cortical activity suggests that ß (16-35 Hz) and γ (75-100 Hz) oscillations could reflect different processes in locomotor adjustments. During task, modulation of γ ERS by substrate orientation (horizontal/vertical) and epoch (preparation/execution) suggests close tuning to movement dynamics and biomechanical demands. ß ERD was essentially modulated by gait (walk/bound), which could illustrate contribution to movement sequence and coordination. At rest, modulation of ß power by substrate orientation underlines its role in sensorimotor processes for postural maintenance.

Secondary somatosensory cortex of primates: beyond body maps, toward conscious self-in-the-world maps.

Recent human imaging studies have revealed the involvement of the secondary somatosensory cortex (SII) in processes that require high-level information integration, such as self-consciousness, social relations, whole body representation, and metaphorical extrapolations. These functions are far beyond its known role in the formation of body maps (even in their most complex forms), requiring the integration of different information modalities in addition to somatosensory information. However, no evidence of such complex processing seems to have been detected at the neuronal level in animal experiments, which would constitute a major discrepancy between human and non-human animals. This article scrutinizes this gap, introducing experimental evidence of human and non-human primates' SII functions set in context with their evolutionary significance and mechanisms, functionally situating the human SII as a primate brain. Based on the presented data, a new concept of a somatocentric holistic self is proposed, represented as a more comprehensive body-in-the-world map in the primate SII, taking into account evolutionary aspects that characterize the human SII and its implication in the emergence of self-consciousness. Finally, the idea of projection is introduced from the viewpoint of cognitive science, providing a logical explanation to bridge this gap between observed behavior and neurophysiological data.

Phase transitions of brain evolution that produced human language and beyond.

The brain capacity of human ancestors underwent two phase transitions, which were supported by preadaptations during the animal protolanguage period, resulting in the emergence of human language. The transitions were (1) the emergence of the primate cerebral cortex, with its unique characteristic of additional cortical areas together with size expansion, and (2) the replacement of natural selection as the main evolutionary mechanism by triadic niche construction, an interactive expansion of ecological-, neural-, and cognitive-niches. These phase transitions accelerated the expansion of the hominid brain, exceeding the neural capacity threshold required for the emergence of language. Extrapolating these developments enabled the researchers to predict a third phase transition, which may be induced by the current explosion of artificial intelligence, accelerating human cognitive capacities to the next threshold required for a novel mode of language.

Fast Electrophysiological Mapping of Rat Cortical Motor Representation on a Time Scale of Minutes during Skin Stimulation.

The topographic map of motor cortical representation, called the motor map, is not invariant, but can be altered by motor learning, neurological injury, and functional recovery from injury. Although much attention has been paid to short-term changes of the motor map, robust measures have not been established. The existing mapping methods are time-consuming, and the obtained maps are confounded by time preference. The purpose of this study was to examine the dynamics of the motor map on a timescale of minutes during transient somatosensory input by a fast motor mapping technique. We applied 32-channel micro-electrocorticographic electrode arrays to the rat sensorimotor cortex for cortical stimulation, and the topographic profile of motor thresholds in forelimb muscle was identified by fast motor mapping. Sequential motor maps were obtained every few minutes before, during, and just after skin stimulation to the dorsal forearm using a wool buff. During skin stimulation, the motor map expanded and the center of gravity of the map was shifted caudally. The expansion of the map persisted for at least a few minutes after the end of skin stimulation. Although the motor threshold of the hotspot was not changed, the area in which it was decreased appeared caudally to the hotspot, which may be in the somatosensory cortex. The present study demonstrated rapid enlargement of the forelimb motor map in the order of a few minutes induced by skin stimulation. This helps to understand the spatial dynamism of motor cortical representation that is modulated rapidly by somatosensory input.

Auditory-Motor Matching in Vocal Recognition and Imitative Learning.

Songbirds possess mirror neurons (MNs) activating during the perception and execution of specific features of songs. These neurons are located in high vocal center (HVC), a premotor nucleus implicated in song perception, production and learning, making worth to inquire their properties and functions in vocal recognition and imitative learning. By integrating a body of brain and behavioral data, we discuss neurophysiology, anatomical, computational properties and possible functions of songbird MNs. We state that the neurophysiological properties of songbird MNs depends on sensorimotor regions that are outside the auditory neural system. Interestingly, songbirds MNs can be the result of the specific type of song representation possessed by some songbird species. At the functional level, we discuss whether songbird MNs are involved in others' song recognition, by dissecting the function of recognition in various different but possible overlapping processes: action-oriented perception, discriminative-oriented perception and identification of the signaler. We conclude that songbird MNs may be involved in recognizing other singer's vocalizations, while their role in imitative learning still require to solve how auditory feedback are used to correct own vocal performance to match the tutor song. Finally, we compare songbird and human mirror responses, hypothesizing a case of convergent evolution, and proposing new experimental directions.

A high-throughput neurohistological pipeline for brain-wide mesoscale connectivity mapping of the common marmoset.

Understanding the connectivity architecture of entire vertebrate brains is a fundamental but difficult task. Here we present an integrated neuro-histological pipeline as well as a grid-based tracer injection strategy for systematic mesoscale connectivity mapping in the common marmoset (Callithrix jacchus). Individual brains are sectioned into ~1700 20 µm sections using the tape transfer technique, permitting high quality 3D reconstruction of a series of histochemical stains (Nissl, myelin) interleaved with tracer labeled sections. Systematic in-vivo MRI of the individual animals facilitates injection placement into reference-atlas defined anatomical compartments. Further, by combining the resulting 3D volumes, containing informative cytoarchitectonic markers, with in-vivo and ex-vivo MRI, and using an integrated computational pipeline, we are able to accurately map individual brains into a common reference atlas despite the significant individual variation. This approach will facilitate the systematic assembly of a mesoscale connectivity matrix together with unprecedented 3D reconstructions of brain-wide projection patterns in a primate brain.

Individual identity and affective valence in marmoset calls: in vivo brain imaging with vocal sound playback.

As with humans, vocal communication is an important social tool for nonhuman primates. Common marmosets (Callithrix jacchus) often produce whistle-like 'phee' calls when they are visually separated from conspecifics. The neural processes specific to phee call perception, however, are largely unknown, despite the possibility that these processes involve social information. Here, we examined behavioral and whole-brain mapping evidence regarding the detection of individual conspecific phee calls using an audio playback procedure. Phee calls evoked sound exploratory responses when the caller changed, indicating that marmosets can discriminate between caller identities. Positron emission tomography with [18F] fluorodeoxyglucose revealed that perception of phee calls from a single subject was associated with activity in the dorsolateral prefrontal, medial prefrontal, orbitofrontal cortices, and the amygdala. These findings suggest that these regions are implicated in cognitive and affective processing of salient social information. However, phee calls from multiple subjects induced brain activation in only some of these regions, such as the dorsolateral prefrontal cortex. We also found distinctive brain deactivation and functional connectivity associated with phee call perception depending on the caller change. According to changes in pupillary size, phee calls from a single subject induced a higher arousal level compared with those from multiple subjects. These results suggest that marmoset phee calls convey information about individual identity and affective valence depending on the consistency or variability of the caller. Based on the flexible perception of the call based on individual recognition, humans and marmosets may share some neural mechanisms underlying conspecific vocal perception.

Accurate motor mapping in awake common marmosets using micro-electrocorticographical stimulation and stochastic threshold estimation.

OBJECTIVE: Motor map has been widely used as an indicator of motor skills and learning, cortical injury, plasticity, and functional recovery. Cortical stimulation mapping using epidural electrodes is recently adopted for animal studies. However, several technical limitations still remain. Test-retest reliability of epidural cortical stimulation (ECS) mapping has not been examined in detail. Many previous studies defined evoked movements and motor thresholds by visual inspection, and thus, lacked quantitative measurements. A reliable and quantitative motor map is important to elucidate the mechanisms of motor cortical reorganization. The objective of the current study was to perform reliable ECS mapping of motor representations based on the motor thresholds, which were stochastically estimated by motor evoked potentials and chronically implanted micro-electrocorticographical (µECoG) electrode arrays, in common marmosets. APPROACH: ECS was applied using the implanted µECoG electrode arrays in three adult common marmosets under awake conditions. Motor evoked potentials were recorded through electromyographical electrodes implanted in upper limb muscles. The motor threshold was calculated through a modified maximum likelihood threshold-hunting algorithm fitted with the recorded data from marmosets. Further, a computer simulation confirmed reliability of the algorithm. MAIN RESULTS: Computer simulation suggested that the modified maximum likelihood threshold-hunting algorithm enabled to estimate motor threshold with acceptable precision. In vivo ECS mapping showed high test-retest reliability with respect to the excitability and location of the cortical forelimb motor representations. SIGNIFICANCE: Using implanted µECoG electrode arrays and a modified motor threshold-hunting algorithm, we were able to achieve reliable motor mapping in common marmosets with the ECS system.

The Brain/MINDS 3D digital marmoset brain atlas.

We present a new 3D digital brain atlas of the non-human primate, common marmoset monkey (Callithrix jacchus), with MRI and coregistered Nissl histology data. To the best of our knowledge this is the first comprehensive digital 3D brain atlas of the common marmoset having normalized multi-modal data, cortical and sub-cortical segmentation, and in a common file format (NIfTI). The atlas can be registered to new data, is useful for connectomics, functional studies, simulation and as a reference. The atlas was based on previously published work but we provide several critical improvements to make this release valuable for researchers. Nissl histology images were processed to remove illumination and shape artifacts and then normalized to the MRI data. Brain region segmentation is provided for both hemispheres. The data is in the NIfTI format making it easy to integrate into neuroscience pipelines, whereas the previous atlas was in an inaccessible file format. We also provide cortical, mid-cortical and white matter boundary segmentations useful for visualization and analysis.

Rapid Identification of Cortical Motor Areas in Rodents by High-Frequency Automatic Cortical Stimulation and Novel Motor Threshold Algorithm.

Cortical stimulation mapping is a valuable tool to test the functional organization of the motor cortex in both basic neurophysiology (e.g., elucidating the process of motor plasticity) and clinical practice (e.g., before resecting brain tumors involving the motor cortex). However, compilation of motor maps based on the motor threshold (MT) requires a large number of cortical stimulations and is therefore time consuming. Shortening the time for mapping may reduce stress on the subjects and unveil short-term plasticity mechanisms. In this study, we aimed to establish a cortical stimulation mapping procedure in which the time needed to identify a motor area is reduced to the order of minutes without compromising reliability. We developed an automatic motor mapping system that applies epidural cortical surface stimulations (CSSs) through one-by-one of 32 micro-electrocorticographic electrodes while examining the muscles represented in a cortical region. The next stimulus intensity was selected according to previously evoked electromyographic responses in a closed-loop fashion. CSS was repeated at 4 Hz and electromyographic responses were submitted to a newly proposed algorithm estimating the MT with smaller number of stimuli with respect to traditional approaches. The results showed that in all tested rats (n = 12) the motor area maps identified by our novel mapping procedure (novel MT algorithm and 4-Hz CSS) significantly correlated with the maps achieved by the conventional MT algorithm with 1-Hz CSS. The reliability of the both mapping methods was very high (intraclass correlation coefficients ≧0.8), while the time needed for the mapping was one-twelfth shorter with the novel method. Furthermore, the motor maps assessed by intracortical microstimulation and the novel CSS mapping procedure in two rats were compared and were also significantly correlated. Our novel mapping procedure that determined a cortical motor area within a few minutes could help to study the functional significance of short-term plasticity in motor learning and recovery from brain injuries. Besides this advantage, particularly in the case of human patients or experimental animals that are less trained to remain at rest, shorter mapping time is physically and mentally less demanding and might allow the evaluation of motor maps in awake individuals as well.