Anxious about rejection, avoidant of neglect: Infant marmosets tune their attachment based on individual caregiver's parenting style.

Children's secure attachment with their primary caregivers is crucial for physical, cognitive, and emotional maturation. Yet, the causal links between specific parenting behaviors and infant attachment patterns are not fully understood. Here we report infant attachment in New World monkeys common marmosets, characterized by shared infant care among parents and older siblings and complex vocal communications. By integrating natural variations in parenting styles and subsecond-scale microanalyses of dyadic vocal and physical interactions, we demonstrate that marmoset infants signal their needs through context-dependent call use and selective approaches toward familiar caregivers. The infant attachment behaviors are tuned to each caregiver's parenting style; infants use negative calls when carried by rejecting caregivers and selectively avoid neglectful and rejecting caregivers. Family-deprived infants fail to develop such adaptive uses of attachment behaviors. With these similarities with humans, marmosets offer a promising model for investigating the biological mechanisms of attachment security.

Trigger of twin-fights in captive common marmosets.

Common marmosets usually give birth to twins and form a social group consisting of a breeding couple and pairs of same-aged siblings. The twins may engage in the first agonistic fights between them, twin-fights (TFs), during adolescence. This study investigated the TFs based on records accumulated in our captive colony over 12 years to elucidate the proximate causations that trigger the TFs. We aimed to determine whether the TF onset mainly depended on internal events (such as the onset of puberty) as previously suggested or external events (such as the birth of the younger siblings and the behavioral change of the group members). Although both events usually occur simultaneously, the birth control method (i.e., manipulation of ovulation and interbirth-intervals by prostaglandin administration to females) could temporally separate these events. A comparison of the onset day and occurrence rate with or without the birth control procedure revealed that TFs were triggered by a combination of internal and external events, that is, external events were the predominant triggers of TF, under the influence of internal events. The timing of TF onset was significantly delayed when the birth of the younger siblings was delayed and the twins grew older under the birth-controlled condition, suggesting that the birth of younger siblings and related behavioral changes of group members, as well as twins' developmental maturation, could trigger TF. Higher TF rates between same-sex twins were consistent with previous studies, reflecting the characteristics of same-sex directed aggression in callitrichines.

Comparison of non-invasive, scalp-recorded auditory steady-state responses in humans, rhesus monkeys, and common marmosets.

Auditory steady-state responses (ASSRs) are basic neural responses used to probe the ability of auditory circuits to produce synchronous activity to repetitive external stimulation. Reduced ASSR has been observed in patients with schizophrenia, especially at 40 Hz. Although ASSR is a translatable biomarker with a potential both in animal models and patients with schizophrenia, little is known about the features of ASSR in monkeys. Herein, we recorded the ASSR from humans, rhesus monkeys, and marmosets using the same method to directly compare the characteristics of ASSRs among the species. We used auditory trains on a wide range of frequencies to investigate the suitable frequency for ASSRs induction, because monkeys usually use stimulus frequency ranges different from humans for vocalization. We found that monkeys and marmosets also show auditory event-related potentials and phase-locking activity in gamma-frequency trains, although the optimal frequency with the best synchronization differed among these species. These results suggest that the ASSR could be a useful translational, cross-species biomarker to examine the generation of gamma-band synchronization in nonhuman primate models of schizophrenia.

Effect of dopamine receptor-related compounds on naïve common marmosets for auditory steady-state response.

Abnormalities of auditory steady-state responses (ASSRs) and the effects of antipsychotic drugs on ASSRs have been investigated in patients with schizophrenia. It is presumed that drugs do not directly affect ASSRs because its abnormalities are associated with schizophrenia. Therefore, to investigate the direct effect of drugs on ASSRs, we established an ASSR evaluation system for common marmosets in a naïve state. Dopamine D1 receptor stimulation (SKF-81297, 2 mg/kg ip) significantly increased evoked power (EP) at 40 Hz. The phase locking factor (PLF) was increased significantly at 20, 30, 40, and 80 Hz. However, administration of a dopamine D1 receptor antagonist (SCH-39166, 0.3 mg/kg ip) resulted in a significant decrease in EP and PLF at 30 Hz. Dopamine D2 receptor stimulation (quinpirole, 1 mg/kg im) tended to increase EP and induced power (IP) at all frequencies, and a significant difference was observed at 30 Hz IP. There was no change in PLF at all frequencies. In addition, dopamine D2 receptor blockade (raclopride, 3 mg/kg ip) reduced EP and PLF at 30 Hz. Subcutaneous administration of the serotonin dopamine antagonist, risperidone (0.3 mg/kg), tended to increase IP and decrease PLF, but not significantly. Taken together, it is possible to compare the differences in the mode of action of drugs on ASSRs using naïve nonhuman primates.NEW & NOTEWORTHY We measured the effects of dopamine receptor-related compounds on ASSR in marmosets. D1 receptor stimulation increased the phase locking factor (PLF) and evoked power (EP), and reduced the induced power (IP). D2 receptor stimulation increased the IP. D1 and D2 receptor blockers reduced the PLF and EP at 30 Hz. Different modes of action of various drugs related to psychiatric disorders were evaluated by administering antipsychotic drugs to naïve marmosets.

Cerebral cortical processing time is elongated in human brain evolution.

An increase in number of neurons is presumed to underlie the enhancement of cognitive abilities in brain evolution. The evolution of human cognition is then expected to have accompanied a prolongation of net neural-processing time due to the accumulation of processing time of individual neurons over an expanded number of neurons. Here, we confirmed this prediction and quantified the amount of prolongation in vivo, using noninvasive measurements of brain responses to sounds in unanesthetized human and nonhuman primates. Latencies of the N1 component of auditory-evoked potentials recorded from the scalp were approximately 40, 50, 60, and 100 ms for the common marmoset, rhesus monkey, chimpanzee, and human, respectively. Importantly, the prominent increase in human N1 latency could not be explained by the physical lengthening of the auditory pathway, and therefore reflected an extended dwell time for auditory cortical processing. A longer time window for auditory cortical processing is advantageous for analyzing time-varying acoustic stimuli, such as those important for speech perception. A novel hypothesis concerning human brain evolution then emerges: the increase in cortical neuronal number widened the timescale of sensory cortical processing, the benefits of which outweighed the disadvantage of slow cognition and reaction.

Neuronal Encoding of Emotional Valence and Intensity in the Monkey Amygdala.

Neuropsychological and neuroimaging studies have suggested that the primate amygdala plays an essential role in processing the emotional valence and intensity of visual stimuli, which is necessary for determining whether to approach or avoid a stimulus. However, the neuronal mechanisms underlying the evaluation of emotional value remain unknown. In the present study, we trained male macaque monkeys to perform an operant conditioning task in which fractal visual patterns were associated with three different amounts of air puff delivered to the cheek (negative) or liquid reward (positive). After confirming that the monkeys successfully differentiated the emotional valence and intensity of the visual stimuli, we analyzed neuronal responses to the stimuli in the amygdala. Most amygdala neurons conveyed information concerning the emotional valence and/or intensity of the visual stimuli, and the majority of those conveying information about emotional valence responded optimally to negative stimuli. Further, some amygdala neurons conveyed information related to both emotional valence and intensity, whereas a small portion conveyed information related to emotional intensity alone. These results indicate that the primate amygdala encodes both emotional valence and intensity, highlighting its important role in the avoidance of dangerous stimuli and animal survival.SIGNIFICANCE STATEMENT Evaluating the emotional value of visual stimuli is essential for animal survival, especially in primates. Emotional value is estimated from the emotional valence and intensity of stimuli, and evidence indicates that the amygdala is likely to play a major role in processing these types of information. To our knowledge, the current study is the first to examine the responses of neurons in the monkey amygdala to visual stimuli that differ in emotional valence and intensity simultaneously. Our data suggest that the amygdala plays an important role in the evaluation of emotional stimuli and in the decision to escape negative and harmful stimuli.

Retrograde Transgene Expression via Neuron-Specific Lentiviral Vector Depends on Both Species and Input Projections.

For achieving retrograde gene transfer, we have so far developed two types of lentiviral vectors pseudotyped with fusion envelope glycoprotein, termed HiRet vector and NeuRet vector, consisting of distinct combinations of rabies virus and vesicular stomatitis virus glycoproteins. In the present study, we compared the patterns of retrograde transgene expression for the HiRet vs. NeuRet vectors by testing the cortical input system. These vectors were injected into the motor cortex in rats, marmosets, and macaques, and the distributions of retrograde labels were investigated in the cortex and thalamus. Our histological analysis revealed that the NeuRet vector generally exhibits a higher efficiency of retrograde gene transfer than the HiRet vector, though its capacity of retrograde transgene expression in the macaque brain is unexpectedly low, especially in terms of the intracortical connections, as compared to the rat and marmoset brains. It was also demonstrated that the NeuRet but not the HiRet vector displays sufficiently high neuron specificity and causes no marked inflammatory/immune responses at the vector injection sites in the primate (marmoset and macaque) brains. The present results indicate that the retrograde transgene efficiency of the NeuRet vector varies depending not only on the species but also on the input projections.

Noninvasive scalp recording of the middle latency responses and cortical auditory evoked potentials in the alert common marmoset.

The common marmoset (Callithrix jacchus), a New World monkey, serves as a useful animal model in clinical and basic neuroscience. The present study recorded scalp auditory evoked potentials (AEP) in non-sedated common marmoset monkeys (n = 4) using a noninvasive method similar to that used in humans, and aimed to identify nonhuman primate correlates of the human AEP components. A pure tone stimulus was presented while electroencephalograms were recorded using up to 16 disk electrodes placed on the scalp and earlobes. Candidate homologues of two categories of the human AEP, namely, the middle latency responses (MLR; Na, Pa, Nb, and Pb) and the cortical auditory evoked potentials (CAEP; P1, N1, P2, N2, and the sustained potential, SP) were identified in the marmoset. These waves were labeled as CjNa, CjPa, CjNb, CjPb, CjP1, CjN1, CjP2, CjN2, and CjSP, where Cj stands for Callithrix jacchus. The last MLR component, CjPb, was identical to the first CAEP component, CjP1, similar to the relationship between Pb and P1 in humans. The peak latencies of the marmoset MLR and CAEP were generally shorter than in humans, which suggests a shorter integration time in neural processing. To our knowledge, the present study represents the first scalp recorded MLR and CAEP in the alert common marmoset. Further use of these recording methods would enable valid species comparisons of homologous brain indices between humans and animals.

Potent and Quick Responses to Conspecific Faces and Snakes in the Anterior Cingulate Cortex of Monkeys.

Appropriate processing of others' facial emotions is a fundamental ability of primates in social situations. Several moods and anxiety disorders such as depression cause a negative bias in the perception of facial emotions. Depressive patients show abnormalities of activity and gray matter volume in the perigenual portion of the anterior cingulate cortex (ACC) and an increase of activation in the amygdala. However, it is not known whether neurons in the ACC have a function in the processing of facial emotions. Furthermore, detecting predators quickly and taking avoidance behavior are important functions in a matter of life and death for wild monkeys. the existence of predators in their vicinity is life-and-death information for monkeys. In the present study, we recorded the activity of single neurons from the monkey ACC and examined the responsiveness of the ACC neurons to various visual stimuli including monkey faces, snakes, foods, and artificial objects. About one-fourth of the recorded neurons showed a significant change in activity in response to the stimuli. The ACC neurons exhibited high selectivity to certain stimuli, and more neurons exhibited the maximal response to monkey faces and snakes than to foods and objects. The responses to monkey faces and snakes were faster and stronger compared to those to foods and objects. Almost all of the neurons that responded to video stimuli responded strongly to negative facial stimuli, threats, and scream. Most of the responsive neurons were located in the cingulate gyrus or the ventral bank of the cingulate sulcus just above or anterior to the genu of the corpus callosum, that is, the perigenual portion of the ACC, which has a strong mutual connection with the amygdala. These results suggest that the perigenual portion of the ACC in addition to the amygdala processes emotional information, especially negative life-and-death information such as conspecifics' faces and snakes.

Cerebral Substrates for Controlling Rhythmic Movements.

Our daily lives are filled with rhythmic movements, such as walking, sports, and dancing, but the mechanisms by which the brain controls rhythmic movements are poorly understood. In this review, we examine the literature on neuropsychological studies of patients with focal brain lesions, and functional brain imaging studies primarily using finger-tapping tasks. These studies suggest a close connection between sensory and motor processing of rhythm, with no apparent distinction between the two functions. Thus, we conducted two functional brain imaging studies to survey the rhythm representations relatively independent of sensory and motor functions. First, we determined brain activations related to rhythm processing in a sensory modality-independent manner. Second, we examined body part-independent brain activation related to rhythm reproduction. Based on previous literature, we discuss how brain areas contribute rhythmic motor control. Furthermore, we also discuss the mechanisms by which the brain controls rhythmic movements.

Evaluation of anaesthetic and cardiorespiratory effects after intramuscular administration of alfaxalone alone, alfaxalone-ketamine and alfaxalone-butorphanol-medetomidine in common marmosets (Callithrix jacchus).

BACKGROUND: Anaesthesia is often required in common marmosets undergoing various procedures. The aim of this study was to evaluate anaesthetic and cardiopulmonary effects of alfaxalone, alfaxalone-ketamine and alfaxalone-butorphanol-medetomidine in common marmosets. METHODS: The following treatments were repeatedly administered to seven female common marmosets: Treatment A, alfaxalone (12 mg kg-1 ) alone; treatment AK, alfaxalone (1 mg animal-1 ) plus ketamine (2.5 mg animal-1 ); treatment AMB, alfaxalone (4 mg kg-1 ), medetomidine (50 µg kg-1 ) plus butorphanol (0.3 mg kg-1 ); and treatment AMB-Ati, AMB with atipamezole at 45 minutes. RESULTS AND CONCLUSIONS: Marmosets became laterally recumbent and unresponsive for approximately 30 minutes in A and AK and for approximately 60 minutes in AMB. The animals showed rapid recovery following atipamezole injection in AMB-Ati. The decrease in heart rate and SpO2 was significantly greater in AMB compared to A and AK. Oxygen supplementation, anaesthetic monitors and atipamezole should be available especially when AMB is administered.

Simian immunodeficiency virus infection and flow cytometric characterization of Japanese macaque (Macaca fuscata) hematopoietic cells.

We characterized Japanese macaque (Macaca fuscata) hematopoietic cells using flow cytometry and identified 28 cross-reactive anti-human antibody clones. Furthermore, productive infection of peripheral T lymphocytes with simian immunodeficiency virus (SIV) in vitro was confirmed by intracellular SIV p27 staining. This study could facilitate using Japanese macaques as models for human hematological and immunological disorders and infectious diseases.

Marmosets: Welfare, Ethical Use, and IACUC/Regulatory Considerations.

Use of marmosets in biomedical research has increased dramatically in recent years due, in large part, to their suitability for transgenic applications and utility as models for neuroscience investigations. This increased use includes the establishment of new colonies and involvement of people new to marmoset research. To facilitate the use of the marmoset as a research model, we provide an overview of issues surrounding the ethics and regulations associated with captive marmoset research, including discussion of the history of marmosets in research, current uses of marmosets, ethical considerations related to marmoset use, issues related to importation of animals, and recommendations for regulatory oversight of gene-edited marmosets. To understand the main concerns that oversight bodies have regarding captive biomedical research with marmosets, we developed a brief, 15-question survey that was then sent electronically to academic and biomedical research institutions worldwide that were believed to house colonies of marmosets intended for biomedical research. The survey included general questions regarding the individual respondent's colony, status of research use of the colony and institutional oversight of both the colony itself and the research use of the colony. We received completed surveys from a total of 18 institutions from North America, Europe, and Asia. Overall, there appeared to be no clear difference in regulatory oversight body concerns between countries/regions. One difference that we were able to appreciate was that while biomedical research with marmosets was noted to be either stable or decreasing in Europe, use was clearly increasing elsewhere.

Expression of progenitor cell/immature neuron markers does not present definitive evidence for adult neurogenesis.

It is agreed upon that adult hippocampal neurogenesis (AHN) occurs in the dentate gyrus (DG) in rodents. However, the existence of AHN in humans, particularly in elderly individuals, remains to be determined. Recently, several studies reported that neural progenitor cells, neuroblasts, and immature neurons were detected in the hippocampus of elderly humans, based on the expressions of putative markers for these cells, claiming that this provides evidence of the persistence of AHN in humans. Herein, we briefly overview the phenomenon that we call "dematuration," in which mature neurons dedifferentiate to a pseudo-immature status and re-express the molecular markers of neural progenitor cells and immature neurons. Various conditions can easily induce dematuration, such as inflammation and hyper-excitation of neurons, and therefore, the markers for neural progenitor cells and immature neurons may not necessarily serve as markers for AHN. Thus, the aforementioned studies have not presented definitive evidence for the persistence of hippocampal neurogenesis throughout adult life in humans, and we would like to emphasize that those markers should be used cautiously when presented as evidence for AHN. Increasing AHN has been considered as a therapeutic target for Alzheimer's disease (AD); however, given that immature neuronal markers can be re-expressed in mature adult neurons, independent of AHN, in various disease conditions including AD, strategies to increase the expression of these markers in the DG may be ineffective or may worsen the symptoms of such diseases.

Cortical Regions Encoding Hardness Perception Modulated by Visual Information Identified by Functional Magnetic Resonance Imaging With Multivoxel Pattern Analysis.

Recent studies have revealed that hardness perception is determined by visual information along with the haptic input. This study investigated the cortical regions involved in hardness perception modulated by visual information using functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis (MVPA). Twenty-two healthy participants were enrolled. They were required to place their left and right hands at the front and back, respectively, of a mirror attached to a platform placed above them while lying in a magnetic resonance scanner. In conditions SFT, MED, and HRD, one of three polyurethane foam pads of varying hardness (soft, medium, and hard, respectively) was presented to the left hand in a given trial, while only the medium pad was presented to the right hand in all trials. MED was defined as the control condition, because the visual and haptic information was congruent. During the scan, the participants were required to push the pad with the both hands while observing the reflection of the left hand and estimate the hardness of the pad perceived by the right (hidden) hand based on magnitude estimation. Behavioral results showed that the perceived hardness was significantly biased toward softer or harder in >73% of the trials in conditions SFT and HRD; we designated these trials as visually modulated (SFTvm and HRDvm, respectively). The accuracy map was calculated individually for each of the pair-wise comparisons of (SFTvm vs. MED), (HRDvm vs. MED), and (SFTvm vs. HRDvm) by a searchlight MVPA, and the cortical regions encoding the perceived hardness with visual modulation were identified by conjunction of the three accuracy maps in group analysis. The cluster was observed in the right sensory motor cortex, left anterior intraparietal sulcus (aIPS), bilateral parietal operculum (PO), and occipito-temporal cortex (OTC). Together with previous findings on such cortical regions, we conclude that the visual information of finger movements processed in the OTC may be integrated with haptic input in the left aIPS, and the subjective hardness perceived by the right hand with visual modulation may be processed in the cortical network between the left PO and aIPS.

Fluoxetine-induced dematuration of hippocampal neurons and adult cortical neurogenesis in the common marmoset.

The selective serotonin reuptake inhibitor fluoxetine (FLX) is widely used to treat depression and anxiety disorders. Chronic FLX treatment reportedly induces cellular responses in the brain, including increased adult hippocampal and cortical neurogenesis and reversal of neuron maturation in the hippocampus, amygdala, and cortex. However, because most previous studies have used rodent models, it remains unclear whether these FLX-induced changes occur in the primate brain. To evaluate the effects of FLX in the primate brain, we used immunohistological methods to assess neurogenesis and the expression of neuronal maturity markers following chronic FLX treatment (3 mg/kg/day for 4 weeks) in adult marmosets (n = 3 per group). We found increased expression of doublecortin and calretinin, markers of immature neurons, in the hippocampal dentate gyrus of FLX-treated marmosets. Further, FLX treatment reduced parvalbumin expression and the number of neurons with perineuronal nets, which indicate mature fast-spiking interneurons, in the hippocampus, but not in the amygdala or cerebral cortex. We also found that FLX treatment increased the generation of cortical interneurons; however, significant up-regulation of adult hippocampal neurogenesis was not observed in FLX-treated marmosets. These results suggest that dematuration of hippocampal neurons and increased cortical neurogenesis may play roles in FLX-induced effects and/or side effects. Our results are consistent with those of previous studies showing hippocampal dematuration and increased cortical neurogenesis in FLX-treated rodents. In contrast, FLX did not affect hippocampal neurogenesis or dematuration of interneurons in the amygdala and cerebral cortex.

Laminar Pattern of Projections Indicates the Hierarchical Organization of the Anterior Cingulate-Temporal Lobe Emotion System.

The anterior cingulate cortex (ACC), surrounding the genu of the corpus callosum, plays important roles in emotional processing and is functionally divided into the dorsal, perigenual, and subgenual subregions (dACC, pgACC, and sgACC, respectively). Previous studies have suggested that the pgACC and sgACC have distinctive roles in the regulation of emotion. In order to elicit appropriate emotional responses, these ACC regions require sensory information from the environment. Anatomically, the ACC has rich connections with the temporal lobe, where the higher-order processing of sensory information takes place. To clarify the organization of sensory inputs into the ACC subregions, we injected neuronal tracers into the pgACC, sgACC, and dACC and compared the afferent connections. Previously, we analyzed the afferent projections from the amygdala and found a distinct pattern for the sgACC. In the present study, the patterns of the afferent projections were analyzed in the temporal cortex, especially the temporal pole (TP) and medial temporal areas. After tracers were injected into the sgACC, we observed labeled neurons in the TP and the subiculum of the hippocampal formation. The majority of the labeled cell bodies were found in the superficial layers of the TP ("feedforward" type projections). The pgACC received afferent projections from the TP, the entorhinal cortex (EC), and the parahippocampal cortex (PHC), but not from the hippocampus. In each area, the labeled cells were mainly found in the deep layers ("feedback" type projection). The pattern for the dACC was similar to that for the pgACC. Previous studies suggested that the pgACC, but not the sgACC receive projections from the dorsolateral prefrontal cortex (DLPFC). These data suggest that the sgACC plays crucial roles for emotional responses based on sensory and mnemonic inputs from the anterior temporal lobe, whereas the pgACC is more related to the cognitive control of emotion.

Evolutionary Elongation of the Time Window of Integration in Auditory Cortex: Macaque vs. Human Comparison of the Effects of Sound Duration on Auditory Evoked Potentials.

The auditory cortex integrates auditory information over time to obtain neural representations of sound events, the time scale of which critically affects perception. This work investigated the species differences in the time scale of integration by comparing humans and monkeys regarding how their scalp-recorded cortical auditory evoked potentials (CAEPs) decrease in amplitude as stimulus duration is shortened from 100 ms (or longer) to 2 ms. Cortical circuits tuned to processing sounds at short time scales would continue to produce large CAEPs to brief sounds whereas those tuned to longer time scales would produce diminished responses. Four peaks were identified in the CAEPs and labeled P1, N1, P2, and N2 in humans and mP1, mN1, mP2, and mN2 in monkeys. In humans, the N1 diminished in amplitude as sound duration was decreased, consistent with the previously described temporal integration window of N1 (>50 ms). In macaques, by contrast, the mN1 was unaffected by sound duration, and it was clearly elicited by even the briefest sounds. Brief sounds also elicited significant mN2 in the macaque, but not the human N2. Regarding earlier latencies, both P1 (humans) and mP1 (macaques) were elicited at their full amplitudes even by the briefest sounds. These findings suggest an elongation of the time scale of late stages of human auditory cortical processing, as reflected by N1/mN1 and later CAEP components. Longer time scales of integration would allow neural representations of complex auditory features that characterize speech and music.

A note on retrograde gene transfer efficiency and inflammatory response of lentiviral vectors pseudotyped with FuG-E vs. FuG-B2 glycoproteins.

Pseudotyped lentiviral vectors give access to pathway-selective gene manipulation via retrograde transfer. Two types of such lentiviral vectors have been developed. One is the so-called NeuRet vector pseudotyped with fusion glycoprotein type E, which preferentially transduces neurons. The other is the so-called HiRet vector pseudotyped with fusion glycoprotein type B2, which permits gene transfer into both neurons and glial cells at the injection site. Although these vectors have been applied in many studies investigating neural network functions, it remains unclear which vector is more appropriate for retrograde gene delivery in the brain. To compare the gene transfer efficiency and inflammatory response of the NeuRet vs. HiRet vectors, each vector was injected into the striatum in macaque monkeys, common marmosets, and rats. It was revealed that retrograde gene delivery of the NeuRet vector was equal to or greater than that of the HiRet vector. Furthermore, inflammation characterized by microglial and lymphocytic infiltration occurred when the HiRet vector, but not the NeuRet vector, was injected into the primate brain. The present results indicate that the NeuRet vector is more suitable than the HiRet vector for retrograde gene transfer in the primate and rodent brains.

Neuroethical Issues of the Brain/MINDS Project of Japan.

The Brain/MINDS project aims to further understand the human brain and neuropsychiatric disorders through "translatable" biomarkers. Here, we describe the neuroethical issues of the project that have arisen from clinical data collection and the use of biological models of neuropsychiatric disorders.