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“Natural Laboratory Complex” for novel primate neuroscience


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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.
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fnint-16-927605 September 29, 2022 Time: 15:58 # 1
TYPE Hypothesis and Theory
PUBLISHED 05 October 2022
DOI 10.3389/fnint.2022.927605
Elizabeth B. Torres,
Rutgers, The State University
of New Jersey, United States
Yuxiang Liu,
University of Texas Southwestern
Medical Center, United States
Keisuke Kawasaki,
Niigata University, Japan
Atsushi Iriki
RECEIVED 24 April 2022
ACCEPTED 23 August 2022
PUBLISHED 05 October 2022
Iriki A and Tramacere A (2022) “Natural
Laboratory Complex” for novel primate
Front. Integr. Neurosci. 16:927605.
doi: 10.3389/fnint.2022.927605
© 2022 Iriki and Tramacere. This is an
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“Natural Laboratory Complex”
for novel primate neuroscience
Atsushi Iriki1*and Antonella Tramacere2,3
1Laboratory for Symbolic Cognitive Development, RIKEN Center for Biosystems Dynamics
Research, Kobe, Japan, 2Department of Philosophy and Communication Studies, University of
Bologna, Bologna, Italy, 3Department of Cultural and Linguistic Evolution, Max Planck Institute for
the Science of Human History, Jena, Germany
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.
longitudinal studies, socio-ecological studies, natural(istic) environment, advanced
technologies, remote infrastructure, primate welfare, dilemma and trade-offs
Neuroscience has made tremendous advancements in understanding the biological
mechanisms and processes of the human mind. A considerable part of these
advancements has been achieved through research in animal models, including non-
human primates (NHPs). Notwithstanding, in the last decades, in most Western
countries, NHP experimentation have faced practical challenges and ethical restrictions,
largely due to difficulties of keeping pace with economic costs of NHPs facilities,
and ethical concerns that primates experience suffering similarly to humans (EU
Commission,2013;Lankau et al.,2014).
Meanwhile, rodents have become (and very likely will continue to be) the
commonest animal model in neuroscience (Homberg et al.,2017), often replacing NHPs
in experiments about mechanisms of cognitive functions. One of the reasons for the
widespread use of the rodent model in neuroscience comes from rodent cognitive
complexity. Astonishingly complex cognitive capacities have been recognized in various
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species of rodents. Rodents are very skilled problem-solver,
have highly developed motor capacities and show a variety
of social and non-social cognitive mechanisms (Davis,1996;
Additionally, pragmatic reasons make rodents very much
investigated in neuroscience labs. Mice and rats are easy to
breed and to test in laboratory settings and have very flexible
behavioral habits, which raise relatively few concerns from an
ethical and practical standpoint (Hickman et al.,2017).
Many have pointed out however that the rodent model is
limited when explanatory targets of the human mind do not find
adequate counterparts in the rodent anatomy and physiology
(Roelfsema and Treue,2014;Camus et al.,2015). Differences
between rodents and humans become even more problematic
if one considers the recent pragmatic turn in cognitive science
(Engel et al.,2016), for which mental functions and dysfunctions
are not exclusively the result of internally regulated brain
mechanisms, but also of brain–body and brain–environmental
interactions. As the mind is progressively understood in terms of
bodily rules and situated aspects of environmental interactions,
approaches that abstract from the specie-specificity of these
aspects in the target animal models become outdated.
Every animal species possesses characteristics and
idiosyncrasies that are difficult to generalize to other animal
species. Therefore, experimentations with animal models
will always show some range of limitations when the goal is
generalizations of mechanisms to humans. No animal model
could ever exactly recapitulate human cognitive capacities.
However, the evolutionary relatedness, as well as the similar
rules of interactions between biological and social factors in
complex environmental niches (Camus et al.,2015), often make
NHPs outstripping candidates for inquiring about processes
and mechanisms of the human mind.
If we agree with this assumption, then we face a dilemma
regarding the role of primates in neuroscience; that is, while
phylogenetic proximity with humans dictates primary relevance
of NHPs, the same proximity produces ethical concerns and
pave the way to difficulties in regulating research practices and
regulations. Taking primate research dilemma seriously implies
that neuroscience needs to balance the trade-offs between
ethical considerations and practical benefits for advancing
the understanding of the evolutionary precursors and basic
mechanisms of the human mind. The dilemma also implies
that, because of the standard of welfare that we want to grant
to NHPs in neuroscience research, any novel proposal for
NHP experimentation shall take into consideration cost-benefits
trade-off for all partners, including the primates (Carvalho et al.,
In this article, we intend to lay the ground for such a project,
by advancing the conceptual basis and technical requirements
for novel strategies in primate experimentation. We start by
briefly overviewing pros and cons of neuroscience research with
rodent and primate models to show that both models can be
instrumental to address different, but complementary research
questions. Then, we propose a novel endurable setup of NHP
experimentation, as an ethically valuable and pragmatically
useful strategy for cognitive neuroscience and neuropsychiatric
research. Specifically, we propose Natural Laboratory Complex
or Natural Labs, as a combination of indoor-outdoor structures
for studying free moving and socially housed NHPs in
natural(istic) environment.
We argue that cognitive neuroscience approaches in freely
behaving animals could increment productive exchanges
between existing conventional approaches of laboratory
investigations. We further make a series of considerations
regarding how Natural Labs could establish beneficial ethical,
financial, and legal trade-offs for leading NHP neuroscience
to the next stage.
Animal models in neuroscience
The rodent model
Mice and rats belong to the order Rodentia, which is the
closest to order Primates in the class Mammalia. Rodents possess
homologous features with human and NHPs, and numerous
similarities at the anatomical, physiological, and organizational
level (Ellenbroek and Youn,2016).
Many neurocognitive mechanisms which are common to
both primates and rodents have been discovered or delved into
through mice and rats research in the last decades, including
fine-grained mechanisms of manual control, vocal plasticity,
and navigation capacities (Davis,1996;Arriaga and Jarvis,2013).
One obvious example of the latter is the discovery of place
cells in the hippocampus of rodent which has opened new
lines of research on memory and spatial cognition (O’Keefe and
Dostrovsky,1971;Thompson and Best,1989).
The diffusion of the rodent models is not exclusively due
to neuroanatomical and behavioral rationalizations, but also to
pragmatic reasons. Mice and rats have characteristics which
make their colonies cost efficient to maintain. In fact, most
rodents are small, are easily housed in laboratory settings, have
short gestation time and large numbers of offspring, rapid
development to adulthood and short life spans (Bryda,2013;
Hickman et al.,2017).
Further, many novel techniques of intervention, such as
tools for genetic modified engineering, have been developed
in rodents, because the rodent model is considered a good
compromise among animal species which approximate human
brain complexity and where these experimental procedures
are more ethically acceptable (Baker et al.,2020). Through
novel techniques, several molecular factors associated to
specific normal or abnormal cognitive states in human beings
have guided mechanist studies in rodents (Kaiser and Feng,
2015). As a consequence, pioneering advanced technologies in
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genome engineering have facilitated the creation of genetically
manipulated rodent models of various psychiatric disorders,
enabling investigations of underlying biological mechanisms (de
Hamilton,2013;Homberg et al.,2016).
Despite the advantages of rodent experimentation in pre-
clinical and clinical research, findings from rodent models
turned out not to be necessarily generalizable into humans
and have resulted in failure to develop treatments of targeted
mental and psychological disorders (Jennings et al.,2016). This
has discouraged some pharmaceutical companies to invest in
neuropsychiatric research which was largely based on earlier
experimentation with rodents, and to downplaying associated
drug trials (Ayesha,2021). The causes for these results are likely
various and heterogenous, see here for some recent analyses of
the question (Fernández,2019).
It is difficult to exclude, however, that differences in
brain structure and functions between human and mice
could be partially responsible for the hurdles of generalizing
neurocognitive mechanisms from rodents to humans (Stephan
et al.,2019). Potential differences regard the number of neurons
in the brain, organization of the cerebral cortex (Figure 1),
resulting patterns of intracortical connections, and the
actions of neurotransmitters and neuro-modulatory pathways
(Herculano-Houzel,2012). These differences might well hinder
straightforward generalization of rodent neurobiological
mechanisms to humans, despite cognitive and behavioral
phenotypes look similar.
Another factor to consider is that in humans the emergence
of psychological and cognitive traits, and vulnerability to
disorders, is conditioned upon interactions of bodily and
developmental factors across individuals, which include
the specificity of the bodily plan and organization, and
the complexity and richness of the socio-ecological niche.
These aspects make human mental functions substantially
different from caged laboratory animals. These differences are
particularly exacerbated for biologically controlled pure strain
rodent models which are bred in caged-based facilities.
In sum, significant differences in the anatomical, brain
and affective systems in small experimental animals and
humans provide strong limitations for modeling and studying
psychological and behavioral dysfunctions in mice and rats.
Therefore, basic and applied investigations of psychological and
cognitive functions which are mostly exclusively conducted in
rodents can be problematic.
Many previous contributions have analyzed pros and cons
of rodent research, and we will not repeat it here. We are
aware that none of the evidence listed above can constitute a
conclusive argument of what rodent research in neuroscience
can or cannot offer for generalization of results to humans.
Consider however that our aim here is not to demonstrate that
the rodent models is per se limited in cognitive neuroscience
research. With this admittedly brief analysis of potentialities and
limitations of rodent research, our scope is only to point out that,
despite critical advancements, cognitive neuroscience research
in rodents is not alone sufficient for understanding the biological
mechanisms and processes of the human mind. We thus think it
is important to develop strategies to overcome experimentation
restrictions in NHP and benefit of the NHP model in cognitive
and behavioral research.
The non-human primate model
Many neuroscientists have highlighted that the primate
models are unparallel animal models in cognitive neuroscience
and neuropsychiatry (Roelfsema and Treue,2014;Zhou,2014),
which offer valuable mechanistic information for how the
human brain works, and for potential psychiatric vulnerabilities.
One obvious aspect regards similarity of brain organization
between most primate species and humans. Whereas rodent
species with significant difference in brain size have the same
relative size ratio of cortical areas, primate species with larger
brain have higher numbers of associative cortical areas, with
consequent more varieties of intracortical connections leading
to drastic expansions of higher-order functional properties
(Herculano-Houzel,2009,2012;Figure 1). This makes at least
some NHP species optimal models for investigating neural
mechanisms of the human mind.
Further, various neurocognitive mechanisms are common
to humans and monkeys, while different in rodents. These
include object recognition capacities, working memory, fine-
grained processes of decision making, the frontal-parietal
processing of visuomotor behavior, the neural basis of
quantification skills, the complexity of social learning, and the
interplay between conscious and unconscious processes, just to
nominate a few (Capitanio and Emborg,2008).
Primate experimentation facilitates studies of the functional
properties of single or populations of neurons involved in
behavior grounded on human-specific bodily plans, and which
contribute to the development of new treatments. Consider for
example, the discovery that electrical stimulation of subcortical
structures alleviates many of the symptoms of Parkinson’s
disease (Collier et al.,2005). These symptoms are linked to the
primate-specific motor organization and are difficult to observe
in species with different sensorimotor characteristics.
Another case regards the discovery of mirror neurons in the
premotor cortex of the macaque monkey (Ferrari and Rizzolatti,
2015), which inspired new experimental hypotheses in Autism
and Schizophrenia, and new therapeutic intervention in patients
e.g., suffering of facial paralysis and Mirror-Touch synesthesia
(Banissy et al.,2009;de Hamilton,2013). In all these cases, the
specific relationship between primate brain structure to bodily
and socially situated functions have been crucial to uncover
mechanisms generalizable to the human mind, paving the way
to critically therapeutic perspectives.
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Diagrams illustrating different organization principle between primates (left) and rodents (right) by comparing brain structures of species with
different body weight and brain sizes within respective mammalian order. Colored areas in brain illustrations indicate primary sensory (red for
somatosensory, blue for visual, and yellow for auditory) areas in representative extant primate (left) and rodent (right) species of body (first
numbers in brackets) and brain (last numbers in brackets) sizes (adopted and modified from Krubitzer,2009;Krubitzer and Dooley,2013). Note
the difference in proportion of these primary areas and association areas (in white) in different sized-brain between primates and rodents. (Ref.
color symbols not directly related to the scope of this article, but illustrated in the original figures: green, motor area; pink, secondary
somatosensory area; light blue, secondary visual area.)
That embodied aspects of human mental functions and
mechanisms can be efficiently investigated in NHPs does
not imply that investigating these aspects in other animal
species is not instructive. For example, mirror neurons have
also been inquired about in rodents (Viaro et al.,2021) and
birds (Mooney,2014;Tramacere et al.,2019) and linked to
respectively manual and vocal behavior. While the comparative
approach in neuroscience is fruitful to inquire into the
biological bases of cognitive variations, it does not dispense of
the lack from primate experimentation. Rather, cross-species
comparison between non-primate species and humans requires
also analyzing the NHP brain connected to primate-specific
evolutionary variations in embodied and socio-ecologically
situated cognition and behavior.
From an anatomical point of view, primates possess
homologous bodily structures with humans making easier to
analyze certain functions related to posture, facial expression,
gaze, and manual gestures, which result from the use of the
body in interaction with the physical and social environment.
Consequently, the morphological commonalities also allow to
inquire the role of environmental and social interactions in the
emergence of cognitive functions and dysfunctions (Chang et al.,
Behaviors such as manual dexterity and tool-use (Iriki,
2006), communication based on the mobility of facial expression
(Tramacere and Ferrari,2016), important aspects of social and
individual cognition (O’Connell and Dunbar,2005;Dunbar,
2009), the mechanisms of attention and visuomotor behavior
(Rizzolatti et al.,2001;Peeters et al.,2009;Yang et al.,2016) are
different among primate and non-primate animals.
Further, from a molecular genetic standpoint, the
phylogenetic proximity of humans and NHPs give more
guarantees that they will share more specific genetic
mechanisms involved in neurophysiology, behavior, and
susceptibility to disease. As NHPs and humans are part of
the same phylogenetic lineage, NHPs have largely shared
gene maps, over other mammalian orders, and therefore can
contribute to analyze complex gene-gene or gene-environment
interactions at the basis of human neurophysiological processes
(Rogers and Gibbs,2014).
To conclude this analysis with a further example, consider a
recent study from Yoshida et al. (2016) with macaque monkeys.
The authors serendipitously noticed that one individual of the
primate group presented a set of behavioral manifestations
that were consistent with autistic-like phenotype in human
beings. These manifestations included primate specific affective
behavior, such as lack of grooming and facial interactions, and
presence of nail-biting stereotypes.
Although grooming in human beings vary across cultures
(Jaeggi et al.,2017), reciprocal cleaning practices, together
with facial exchanges and stress-related nail biting are primate
(including human)-specific behaviors that cannot be observed
in animal species with different bodily and socio-environmental
components. We take this study as an example to suggest that
the primate model is important to understand the emergence of
cognitive mechanisms and functions that are common to human
and NHPs and illustrate how they are involved in the emergence
of psychiatric conditions.
Note however that NHP experimentations have
disadvantages in cognitive neuroscience and neuropsychiatry.
NHPs are larger than laboratory rodents, thus experiencing
discomfort when living in cages, especially because social
interactions and active exploration of the environment are
essential to their development and psychological wellbeing
(Conlee and Rowan,2012). Further, as previously mentioned,
NHP experimentation produce concerns from an ethical point
of view, because of evidence that primate species experience
suffering in a similar way to humans.
Among the disadvantages of primate experimentation,
technical challenges must also be considered. Not all
investigative tools are easily utilized in the NHP models. For
example, optogenetics, a genetically coded channel technique
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that allows high temporal and spatial resolution of cortical and
cerebellar brain circuits, have faced a slow progress in NHPs
(Galvan et al.,2018). The same is true for other techniques,
such as for example chemogenetics (Raper and Galvan,2022),
and transgenic tools (Coors et al.,2010), which are thought to
produce unacceptable suffering and pragmatic difficulties in
In the next sections, we will capitalize on the pros and cons
of primate and rodent research to propose a novel strategy
of primate experimentation that can increase productive
exchanges between experimental sub-fields conducted with
different animal models.
Optimizing cognitive neuroscience
research with animal models
Research on animal models depends on many factors, such
as the nature of the questions and the characteristics of the
species. However, based on the pros and cons of rodent and
primate models briefly depicted thus far, some generalizations
are possible. By considering both characteristics of the models
and of the current practices of research, rodent and primate
research can serve different (and perhaps complementary) aims
in neuroscience and neuropsychiatry.
Many primate species share analogous principles of brain
organization with humans, homologous body plan and similar
rules of interactions between social and biological (i.e., genetic)
factors. Further, human psychological and cognitive traits, and
vulnerability to disorders, result from human evolutionary
history, and are conditioned upon the complexity of the
environmental and social world. The potential of primate
research, and the limitation of rodent experimentation, thus
critically depend on the importance of the ecological, embodied,
and situated aspects in the development of the human mind.
When the overarching goal is to understand the basic
mechanisms of the human mind and the target of research
is primate-specific neurocognitive factors, NHPs are likely
to be optimal candidates for cognitive neuroscience and
neuropsychiatry. In the perspective of a basic, pre-clinical and
clinical neuroscience which must take into consideration the
social, bodily, and environmental context of brain development
and function, research in NHP is going to be going to provide
information that are not possible to achieve through rodents.
Research with rodents (and eventually with other non-
mammals) can be used to inquire into conserved evolutionary
mechanisms or convergent functions that are realized through
instantiation of different brain mechanisms. In addition, based
on the genetic, anatomical and socio-ecological similarity
between human and certain NHP species, NHPs shall be
investigated in a way that is deeply embedded in and integrated
with NHPs’ naturalistic settings, to inquire into the primate
brain and behavior in an ecologically, longitudinally, and
socially valid approach.
Experimentation of NHPs in naturalistic settings is currently
an underdeveloped field of research, which may fill existing
gaps between classical lab research in neuroscience and wildlife
investigations, where these gaps can be defined as a lack of
harmonization and systematic exchanges between respective
research sub-fields (Figure 2A). Laboratory neuroscience, as
a branch of the biomedical field, normally tries to identify
reproducible and generalizable causal brain mechanisms, by
decomposing structurally or functionally the target mental
phenomena through controlled conditions. In contrast, wildlife
studies rely on inquiring into the diversity and individual
uniqueness of animal lives in natural environments, through
descriptive observations of their behavior without intervention.
The laboratory and wildlife approaches retain important
differences also at the ethical level (see Figure 3A and
Box 1). Whereas laboratory statistically controlled conditions
are instrumental to the quality of research practices, they also
automatically imply that animals are subjected to them. These
conditions include isolation from peers and deprivation of social
interactions, living in captivity, research training with repetitive
behaviors which are often not intrinsically rewarding, and so
forth. In contrast, naturalistic and often descriptive observations
of animal behavior normally require no intervention and
operate easily by respecting animal welfare.
We think that in between the gaps at the ethical and research
level resides a strategic potential to integrate relevant research
fields through primate experimentation. Specifically, we propose
Natural primate labs as a combination of open and enclosed
spaces, where NHP populations can live in group and move
freely in a setting of (or resembling) their natural habitat.
These spaces would be open to the use of non-invasive or
minimally invasive methods of brain, behavioral and bodily
markers investigation.
The aim of these Natural Labs is to capitalize on the
descriptive approach of wildlife studies, by focused observations
of NHP behavior in naturalistic conditions (Figure 3B). At the
same time, the mechanistic approach to specific NHP cognitive
functions through the use of brain techniques can allow holding
some of the benefits of the laboratory approach. These two
elements (descriptive and mechanistic) may put primate Natural
Labs in a fruitful communication with the traditionally opposite
frameworks of wildlife and laboratory research (Figure 3C).
Primate Natural Labs can allow to fruitfully connect
different research approaches through the use of a range of
techniques to investigate primate brain, behavioral and bodily
manifestations (which we will describe in the next section).
The combination and flexible integration of novel strategies of
primate experimentation in Natural Labs becomes even more
critical if we consider that, when released into naturalistic
environment, animal models start exhibiting much richer and
more complex behaviors than in cages [see for example, the
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Through the implementation of the Natural Laboratory Complex by the present proposal, it may be possible to increment exchanges between
different research fields. (A) Schematic representation of current research situation, depicting three sub-fields of primate research: wildlife
studies, laboratory experimentations (on the left), and non-primate animal model reduced experimentations, rodents or otherwise (on the right).
Communication and exchange between these three components are not systematic and left to personal exchanges among individual
researchers. (B) Natural Laboratories Complexes can provide bridges between existing experimental sub-fields. Specifically, investigation of
behavior, biological samples and brain activity in Natural Labs can be instrumental to (a) design classical laboratory experiments under
controlled conditions, which can inform additional experimental designs in Natural Labs; (b,c) investigate analogous mechanisms in primate and
non-primate animal models to identify potential conserved functions, and use results of these experiments to inform analysis and models
related to findings obtained in Natural Labs.
documentary of Berdoy (2017)] (Bottom et al.,2020). Therefore,
quantitative comparisons between free-moving and captive
primate and non-primate animals, could inform focus on
appropriate target mechanisms of behavior.
Finally, NHP experimentation needs to be adjusted for
a broad range of neuroscience investigation, that could
complement the research that is already done in laboratories
with human, primate, and rodents, and in the wild with
primates. This is where the integration with classical
laboratory research, in both primate and non-primate
models, become important and can pave the way to the
investigation of phenomena that could not be displaced in
classical research settings.
Novel strategies for primate
Because in Natural Labs primates live freely in naturalistic
spaces, the realization of these structures could allow for the
collection of data in a multimodal, longitudinal, and ecological
perspective, leading to analysis of various types of behaviors and
their underlying neurobiological mechanisms.
In this settings, close collaboration with husbandry and
research personnel as equal partners is important to conduct
breadth of studies from observational ones (to observe and
record animals’ behavioral manifestations) to neurocognitive
investigations (to approach animals and perform cognitive,
neural and biological examinations), because animal hosted
in these structures need appropriate cleaning, space and
nutrition measures. Therefore, husbandry efforts to secure
behavioral manifestations will necessarily become continuous
with research practices, and research endeavor will become a
part of husbandry, thus equally amalgamating both sectors.
The idea of making husbandry continuous with research
efforts is partly similar to what William Conway called
“interactive management” of zoos and natural habitats (Conway,
1995). Conway defined interactive management as a strategy
for both species and habitat preservation that relies upon
the coordination of species living both in a combination of
natural and artificial settings. Interactive managements usually
combine the resources of wildlife managers with those of
biologists working in zoos to ensure that animal individuals
are provided with opportune conditions, and do not suffer for
abrupt environmental or habitat changes.
Our proposal of a novel strategy for primate research in the
wild or in natural-like settings has a different aim but rely on a
similar rationale, because primate species in Natural Labs shall
live in mixed natural-artificial conditions for research purposes,
and not for conservation efforts per se. Although the type of
primate research that we are proposing can lead to conservation
advantages (which we will touch upon later), it primarily
concerns an ethically and pragmatically more sustainable way to
conduct neurobiological and ethological research on our closest
relatives (also see Box 2).
Someone could object that close collaboration between
husbandry and research personnel as equal partners might be
difficult. This is because, in the existing animal experimentation
contexts, conventionally trained researchers do not directly take
care of the practical needs of their animal models, and animal
care taking staffs are normally neutral about the scopes of the
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Comparative representation of ethical and experimental frameworks in various domains of animal research, along progressive development of
interactions among multiple sectors (see Box 1 text for further explanations).
BOX 1 Harmonization of ethical and research gaps.
Animal welfare and human benefit are in opposition depending on the field of research. Different fields often require different approaches to animal
rights and welfare.
Figure 3A illustrates separation of methodologies between the existing biomedical (orange circle; middle) and the wildlife studies (blue circle; top). Gaps exist
between these studies (blue arrow), because biomedicine maximizes human benefits, while wildlife studies are more respectful of primate welfare. Therefore, large
efforts are put to balance and compromise between animal welfare and human benefit with ethic regulations and guidelines, which consider harm-benefit trade off
and 3Rs (replacement, reduction, and refinement) to minimize suffering of laboratory animals. This situation changes once cognitive neuroscience and
neuropsychiatric research (pink circle; middle) comes to interplay (Figure 3B), because it can lead to bridging wildlife (blue circle; top) and biomedical (orange
circle; bottom) studies.
By implementing primate research in naturalistic settings (green circle; with similarity with domesticated and working animals, i.e., nursing, companion,
assistance, guide-animals, etc.; and conditions), the open field of primate cognitive neuroscience and neuropsychiatric research (Natural Labs) emerges to be
carried out at the intersection of the existing research sub-fields (Figure 3C). Here, the use of a variety of novel (minimally invasive) techniques can grant the
mechanistic approach of biomedical research, while primates living in natural settings can benefit of conditions that are normally proper to descriptive wildlife
studies. In this way, neuroscience research in Natural Labs overlaps with both formerly separated wildlife and biomedical research, and reduces the “gap” between
animal welfare and human benefit. Through Natural Labs, former polarizations between primate and human welfare, and mechanist and descriptive approaches
become continuous. The application of new technology, subserving this new field can affect also the other field of research to trigger a novel (methodological and
ethical) paradigm.
experiments, perhaps in order to avoid any implicit bias to affect
on the scientific research outcomes using laboratory animals.
Coordinating the collaboration between husbandry and
research sectors requires focused reflection and dedicated
strategies, that go beyond the scope of this article. We would
like to provide however one potential clue. In order to secure
husbandry efforts for behavioral manifestations as a portion
of research, and of research activities comprising a part of
husbandry, strategies could be extrapolated from the mode of
human commitments in collaborations with working animals
(i.e., nursing, companion, assistance, guide-animals, etc.) in
which caretaking and behavior analyses/control is undertaken as
an integrated endeavor, in an environment somewhat resembles
the laboratory conditions.
Natural laboratory complex
In order to realize the proposed research strategies,
studies should be designed to be conducted in structures
comprising field sites in natural settings (in situ Lab-in-Nature)
and laboratories resembling primate natural habitats (ex situ
Nature-in-Lab), both of which are equipped with advanced
technologies appropriate to observe and investigate NHPs’
brain, biology and behaviors. We describe the technologies that
could be used in the Natural Laboratory Complex, together with
how they could balance cost and benefits trade-offs at the ethical
and economic level.
In situ Lab-in-Nature
Various types of technologies could be used in Natural
Labs to investigate primate neurobiological and behavioral
functions. Here, we elaborate on some examples to offer
ideas of how these indoor-outdoor research space could be
technically organized.
Firstly, a few deep learning algorithm techniques, each
tailored to the research question, can be employed to estimate
behavioral poses in monkeys interacting in the social group or
during specific tasks (Nath et al.,2019;Lauer et al.,2022). These
data could be integrated with fine-grained behavioral analysis
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BOX 2 Rationale and examples of Natural Labs.
The concept of Natural Labs relies on the awareness that the traditional view of protecting animals by letting them live in a vast self-sustaining “wild need to be
rethought. We must begin to face the reality of a world that is and will remain vastly altered by human activities. Consequently, taking actions for ensuring that
many more wildlife communities can survive if they are intensively cared as a form of “megazoos” (Conway,1995) could be more efficient than being stacked in
searching a wildlife for animals untouched from human intervention. The interactive management proposal is thus a wide way for zoos, working with local
communities to support the survival of species under risk of extinction.
The idea of Natural Labs for primate experimentation can be framed in this perspective. One obvious example of Natural Labs is the primate bio-park. They are
zoo-like spaces for hosting various species of NHPs, and where it is possible to collect multiple socio-behavioral, neural, and molecular information associated to
cognitive phenomena in a longitudinal perspective, and in accordance with the application of novel technologies. NHP populations hosted in these bio-parks
mimic natural population living in the wild and constitute a natural source of variability that may be critical for achieving mechanist models of cognitive and
behavioral development.
The most similar examples of bio-parks we are here illustrating can be found in the Pongoland Wolfgang Köhler Primate Research Center, which operates in
collaboration with the Leipzig zoo, or in The Apenheul Primate Park in the Netherlands. Both of them are zoos where visitors can see and interact with different
species of primates, but they also house a research center, where different types of investigations are conducted. To make these bio-parks more similar to our
proposal, they should be equipped with technologies for experimenters to inquire the primate neurobiology beyond the observation of behavioral aspects.
Incidentally, genetic biodiversity in these parks may be guaranteed through periodic assisted reproduction in females, or through migration of male or female
specimens, in accordance with the sexual behavior of the considered species.
Another form of Natural Labs would require that scientists conduct research in the primate natural environment. This would require the establishment of what
has been called hotel space next to primate natural environment, where visiting researchers can carry out various types of experiments. Telecommuting approaches
may be utilized to share information with scientists on site (Jennings et al.,2016).
We are referring to the types of novel technologies that allow the storage and transfer of information in real-time, such as Internet of things (i.e., a new paradigm
in modern wireless telecommunication) (Atzori et al.,2010), IT based knowledge management (i.e., information technology system to enhance and organize
knowledge) (Alavi and Leidner,1999), and cloud-based Big Data processing for allowing cost-efficient exploration for voluminous data set (Fang et al.,2015).
Alternatively, scientists could utilize telecommunication technologies (i.e., remote labs) from a separate geographical location, to remotely conduct real
experiments at the physical location of the operating technology (Quesada-González and Merkoçi,2017).
The rationale of the hotel space with remote technologies can be appealing also to investigate the number of NHP individuals living wildly or semi-wildly in
countries, such as Japan, Singapore or anywhere close to primates’ natural habitat. In Japan, for example, several monkey parks are spread throughout the territory
and are open to visitors. In Singapore, although not specifically for primates, there are many Safaris where animals live in wild-like environment and are managed
by caretakers under international standards of animal welfare. These animals can constitute a further source for studying inter-individual variability at the
behavioral level, and analyzing various biological samples (e.g., from the feces to the blood or the buccal mucosa).
in socio-environmental set-ups (Nishikawa and Kinjo,2018),
allowing investigation of previously unavailable ecological
Fully non-invasive AI (artificial intelligence)-based motion
capture of monkeys in the wild, deriving VR (virtual reality)
and IT (internet technologies) for sharing and analyses of those
motion data may be important technologies for integrative
neuroscience investigations of in situ Lab-in-Nature. The social
or individual behavior of primates could be recorded and
analyzed by fixed-point live digital cameras installed at the
field site and subjected to AI-based motion capture and
3D reconstruction using online deep transfer learning-based
automated motion analysis technologies (Nath et al.,2019;Lauer
et al.,2022).
Non-human primate behavioral datasets could be
embedded (as avatars) in digitized environmental information
(i.e., laser-scanned landscape, vegetation, meteorological
conditions by remote-sensing devices, etc.) using VR
technologies to comprise Real-time 3D Digital Zoo
accessible to world-wide academic professionals for
research purposes through IT-based cloud technologies,
which have achieved prevalent development under current
COVID-19 restrictions of inter-regional traffics. This set
of technologies could contribute to organize effective
and efficient international collaborations to fully utilize
this opportunity.
In addition, molecular biological information of subject
NHPs in the natural environment (i.e., population genomics,
epigenetics, microbiome, nutrition isotope, etc.) can be
collected, and correlated with above in situ socio-behavioral
characteristics of individual animals, to tracking mechanisms
of ecological and social variations. Patterns of molecular
expression can be measured through the analysis of a variety
of discharged bio-samples (feces, saliva, and hair) (Sawaswong
et al.,2020), or of exhalation by laser spectroscopy (Selvaraj
et al.,2020). Close collaborations with researchers and local
personnel (such as staffs of natural parks at NHP habitat)
to design the observation system and sample collection,
as well as to maintain and operate sensing devices at
the filed sites are mandatory to make this infrastructure
Finally, at the physiological and neural levels, a number
of novel tools can be used. For example, ultra-thin film bio-
sensors attached to the body surface (Nishinaka et al.,2021)
and a number of emerging technologies allowing measurements
of brain activities through embedded wireless multi-electrode
and electrocorticography techniques (Matsuo et al.,2011;Ando
et al.,2016) or miniature PET (positron emission tomography)
technologies (Schulz et al.,2011) could be utilized. Although
these investigations would only offer correlational information
and not controlled causal pathways, a number of dynamical
networks techniques (Bramson et al.,2019;Aihara et al.,
2022) can be applied to detect plausibility of multi-level causal
pathways (Stokes and Purdon,2017).
The hypothesized causal pathways between variables
obtained in Natural Labs at multiple level of analysis (from
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behavioral to molecular) can be useful to design controlled
experiments in captivity with primates that are hosted under
traditional laboratory facilities (Figure 2Ba). In addition, basic
elements of these pathways can be investigated under traditional
laboratory settings in non-primate animal models, with the
goal of inquiring into potential conserved mechanisms present
across species (Figure 2Bb,c). In this way, Natural Labs
(with both in situ- and ex situ-, to be depicted below) can
constitute a bridgehead between classical laboratory and wildlife
research approaches (Figure 2B): the multilevel investigations
executed on primate groups in natural(istic) settings would
provide results and findings to inquire into NHP and non-
primate models under controlled conditions in classical captive
Ex situ Nature-in-Lab
Above in situ Lab-in-Nature is not adapted for neuroscience
experimental interventions. A compatible and complementary
laboratory setup that simulates (perhaps by being located
close to) natural environment and house minimal numbers
of NHPs (namely, ex situ Nature-in-Lab) could be established
to allow longitudinal scientific investigations with minimally
invasive neuroscience techniques. In ex situ Nature-in-
Lab, scientists can study the mechanistic basis of various
cognitive functions; perform, along the developmental
lifespan of the primate individuals large-scale genetic,
epigenetic and metabolite screens; interrogate circuit-level
processes of mental functions; and keep tracking of the
social behavior of various individuals constituting a primate
population group.
In ex situ Nature-in-Lab, scientists can collect a large
number of heterogeneous data and conduct analysis of
multilevel information (from genetic profile to neuronal
circuitry, to social behavior), through large-scale investigation
of brain, body, cognitive, and behavioral traits. This has the
potential to enable systematic characterization of molecular,
cellular and circuit-level landscapes of the primate brain and
behavior across development and context.
Similar research settings have been utilized in the last
decades for testing primate cognitive and behavioral abilities
through Computerized Test Systems, which allow animals
to live with their social group and to enter some test
stations at some time points of the day (Perdue et al.,2018).
However, experimental tests in these spaces rarely include
neural and molecular investigations; cognitive, neural, and
genetic analyses mostly pertain to different laboratories that
study biological or imaging samples. In contrast, Natural Labs
should be intended as spaces where it is possible to train
novel, minimally invasive techniques in complex environments,
with the aim to collect information that are not possible
to obtain in classical laboratory settings, therefore factually
being a step forward in the type of information available for
Again, like in situ Lab-in-Nature, close collaboration with
researchers and husbandry personnel is important to promote
maximum scientific potential of the ex situ Nature-in-Lab. That
is, ways to maintain colony in this setup is a part of experimental
design and collecting quality scientific data can be completed
through daily husbandry activities. Also, collected data could be
made accessible real-time on-line, via internet, from laboratories
located remotely world-wide in which scientists are interested in
further analyses of their interest. Hotel space might be associated
with ex situ Nature-in-Lab for occasional site visits for such
remote scientists whenever physical activities are required on
site, and perhaps also to make comparative investigations in
relation to closely located complementary in situ Lab-in-Nature
(Tramacere and Iriki,2021).
Natural Labs with novel technologies would become world’s
hub of laboratories conducting novel research paradigms. In
order for such Natural Labs to become a bridgehead between
different research approaches, conceptual foundations need
to be established to defend following criticisms from mind-
sets of current experimental paradigms. Objections could
range from lack of experimental sessions, lack of reproducible
results under strictly controlled conditions (e.g., fixed head
recordings with operantly conditioned tasks in identical
experimental environment), or difficulties for applying methods
to record neural activity. Importantly however, the present
proposal does not aim to completely substitute, but to initially
complement existing primate laboratory research. Therefore,
neuroscientists can still have the possibilities to conduct primate
experimentation in a classical laboratory setting when it is
necessary to do so.
On the other hand, classically positioned primatologists
may object that is aberrant to violate the life of the animals
hosted in semi-natural environments or in the wild. We
agree this is a fundamental issue that needs to be addressed
through careful discussions. It seems obvious, however, that
only a limited number of observations and experiments should
be made possible in NHPs living in natural conditions,
carefully considering only measures for minimal invasiveness
and disturbance, which are very much in accordance with the
widely accepted welfare rules in primates.
In the next section, we will delve deeper in the cost-benefit
trade-off that this novel strategy of primate experimentation
would require, both at the ethic and scientific level.
Harmonization of cost and benefit
Ethical balance
Natural Laboratory Complex (combinations of ex situ and
in situ Natural Labs) fulfills current ethical standards (CIOMS-
ICLAS,2015) but also provide increased ethical conditions
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for primates. This is because, on our proposal, researchers of
in situ Lab-in-Nature would team up with wild-life conservation
sectors, and of ex situ Nature-in-Lab work together with
husbandry team, to ensure obtained data to represent primates’
ecological characteristics, whereby incorporate into extant
animal experimentation frameworks (Figure 3) has embedded
within it the means to merge formerly segregated wildlife and
laboratory research.
From a strictly primate welfare perspective, housing NHPs
in natural-like environments, such as ex situ Nature-in-Lab,
would relief at least some of them from most of the current
costs they are paying for neurobiological research, such as
being removed and bread distant from their natural and social
environment, transported, and subjected to the living conditions
of the facilities.
This proposal would be suitable only for the primates
subjected to neurobiology studies in the labs, which utilize
about the 19% of the total of NHP used in research (Carlsson
et al.,2004). However, its potential benefits should not be
underestimated. In fact, according to the report of United
States Department of Agriculture 2017, a consistent number of
primates are held by facilities but not used in any experimental
protocols (Grimm,2020).
This would imply that a minor number of NHPs could be
housed in facilities in the future for the scope of behavioral
and neurobiological research and produce a situation in which
it would be humans who move to study primates, instead
to move primates in order to be studied by humans. This
is in line with an interpretation of welfare, which not only
aims to avoid or minimize pain and adverse effects, but
also to maximize well-being, through the implementation
of environmental enrichment and the promotion of positive
elements of comfort and security.
Another benefit of the Natural Labs proposal would
derive from its possible effects in terms of primate welfare
and conservation. According to our proposal, research
infrastructures would be established in the wild (in situ Lab-in-
Nature) and would provide a research basis for neuroscientists
and molecular biologists, other than for classical primatologists.
Implementing Natural Labs would thus have the consequence
to increase the amount of field research, and the amount of
information related to primate individuals who live in the
wild that can be utilized for scopes that could benefit primate
welfare in the wild.
Specifically, monitoring the conditions and changes of
primates living in the wild may have positive influences on the
enterprise associated to wildlife conservation and protection
against extinction risks. Because of the documented sudden
leaps in aberrant ecosystem behavior, wild populations of
NHPs become increasingly susceptible to stochastic genetic,
demographic changes, new infectious diseases, and destructive
infestations of invasive insects. A detailed understanding of
animal biology, ecology, life history, behavior, habitat needs,
evolutionary flexibility, and phenotypic plasticity is necessary
for promoting their conservation, and preventing extinction
dangers (Estrada et al.,2017).
The protection of non-human life and ecological processes
necessarily pass through an opportune knowledge of animal
and habitat conditions. Therefore, large-scale molecular and
behavioral analyses in wildlife through the establishment of
research infrastructure can be utilized for tracking extinction
dangerous in primate species, their level of distress and other
indicators of wellness (Paquet and Darimont,2010). In addition,
by inquiring more in details NHP wildlife behavior, through
focus observations or the use of tissue-sample analysis, it is also
possible to acquire information that are critical for reproducing
naturalistic settings for NHP living in natural parks. Knowledge
of the behavior of the animals in the wild it is in fact critical
to understand their needs and necessity while they live in semi-
natural environments.
Non-human primate living in naturalistic settings
may further offer the possibility to investigate a range of
naturally occurring dysfunctions in NHPs. In fact, primates
show inter-individual variability and differential susceptibility
to mental diseases, which can be inquired in order to understand
cognitive mechanisms and functions. An example regards the
spontaneous development of autistic- or depressive-like
phenotype in macaque monkeys (Yoshida et al.,2016). When
sample sizes are sufficient, the observation of social behavior
in monkeys is likely to be useful in latent variable models
that combine indicators of various psychopathologies across
multiple levels of analysis (Maestripieri and Lilienfeld,2016).
These cases may constitute precious source of information
for biomedical research through medical device testing, drug
development and imaging technique refinement.
Socioeconomic balance
Natural Labs might appear costly and hinder continue
running on-going experimentations under currently existing
academic funding schemes. However, introduction of latest
AI, IT, and VR technologies (see section “Natural laboratory
complex”) offer Natural Labs an opportunity for collaborations
with various research sectors, including non-academic
sectors, such as various industries and regional economy,
to attain autonomous financial foundations for its shared and
mutual benefits still yet securing academic independence of
research communities.
Such models could include “Real-time 3D Digital Zoo”
in entertainment businesses, or the one by governmental
supports allowing visitors to the educational programs to be
settled in the Natural Labs within a traditional zoo/safari
perspective (see also Box 3 for potential schemes of cross-sector
collaborations). Hence, these self-supported Natural Labs would
enable researchers in countries far from NHP natural habitat,
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BOX 3 Development of sustainable business–academia–government collaborations.
Biodiversity education for the Natural Labs local site population is paramount to preserve the natural equilibrium of native ecosystems with tourism providing cash
input. Online interactive datasets could be created to construct a “Real-time 3D Digital Zoo” as an ex situ global research center located adjacent to the Natural
Labs. Technological development for this research will contribute to environmental protection with future profitability. Data comprising “Real-time 3D Digital
Cloud Zoo” will be shared between the scientific community and various business models.
A novel neurobiological principle established through the Natural Labs characterizes human gene-culture co-evolution through environmental interactions.
Novel non-invasive technologies (perhaps AI and VR-based) developed through these studies will fulfill the requirements of primate research ethics and wildlife
conservation. This will also emphasize how humanity can evolve as a part of holistic ecosystems and allow us to envision how our biodiversity should be developed
in the future within this ever-changing world.
This research setup can immediately detect “skeleton” behaviors of monkeys for motion analyses, together with rough geometry of the landscape for interactions
with the environment at each Natural Labs site. While this data will comprise core information to establish the “Digital Cloud Zoo, it would be ideal if supports by
businesses and industries to create further sophisticated appearances of the animals and landscape suitable for exhibition to the public. Also, initial setup is limited
to only a small part of the nature for research, and thereafter industry and government-supported collection of data covering larger areas of the local natural habitat
will promote more systematic and wider range of knowledge eventually contribute to preservation of the species across the habitat.
Extension of these scheme desires to create mechanisms that reveal basic data and share findings with the worldwide research community (this is of particular
importance to establish novel global ethical standards for primate research that contribute to future studies for human mental welfare). Procedures enabling this
research-oriented “Digital Cloud Zoo” will share common IT and cloud technologies for exhibition at museums run by local governments, which can further
promote this research through entertainment and businesses that can reach global audiences.
Thus, it would be ideal to institute mechanisms that are equally beneficial for research, government, and industry/business partners. This could be in turn
contribute to scheme governmental policies to plan a new strategy that will include ecotourism and employment of local people to serve as a natural resource for
the local countries.
with minimal expenses for participation, to access data remotely
at home laboratories, and hotel space at Natural Labs offers
conductive possibilities for studying various natural behaviors
of NHPs on site.
Another benefit of this approach is related to those countries
endowed with natural habitats for NHP, such as Japan, India, or
Southeast Asian countries, which suffer from increasing conflict
between humans and feral monkeys over the last several decades
(Dittus,2012). NHPs become pests because they pilfer food and
water near human habitation. Artificial feeding leads to changes
in monkey behavior, resulting in overpopulation of aggressive
monkeys. Exterminating a large number of these monkeys is
unethical according to religious beliefs, and also according to
the welfare standards developed in several countries.
Further, castration and trans-location practices are overly
expensive and laborious because they require specialized
personnel and long-lasting procedures. In Japan, for example,
several monkey parks are spread throughout the territory and
are open to visitors. In Singapore, although not specifically
for primates, there are many Safaris where animals live
in wild-like environment and are managed by caretakers
under international standards of animal welfare. Revenues to
Natural Labs from above business models could create similar
mechanisms for social visiting and education benefits, and
these animals can constitute a further source for studying
inter-individual variability at the behavioral level and analyzing
various biological samples.
Legal balance
A novel factor of the present proposal of Natural Labs which
requires additional consideration is the management of the
data acquired here are shared globally across multiple parties
under having potential conflict of interest. This is an essential
requisite due to its geographically biased natural distribution
of NHPs by ecological limitation, which is complemented by
web-based international data sharing among various sectors.
While such situation secures transparencies to fulfill ethical
and scientific standards of subjected experimentations, at the
same time risks protection of intellectual properties, originality
and privacy of ideas that might belong to parties (individuals,
groups, institutions, nations, etc.) who participate in the project.
Rules to legally harmonize conflicting interests among
such parties yet need to be established [Iriki quoted by Marx
(2016)]. Such harmonization should include legal measures of,
(a) how to ensure priority of shared data among international
academic members across borders of national sovereignty
and security, (b) how to protect intellectual properties, if
any emerged, upon data sharing among industry, academia,
and other relevant sectors, (c) how to manage, or restrict,
balances between scientific accuracy/significance and public
stakeholders’ interests/perception especially when related with
socioeconomical aspects or public policies. Considering novel
aspects of presently proposed Natural Labs paradigms, we
just exemplify these, among many other potential issues, for
future considerations to be incorporated into international
public policy frameworks, in addition to digital technologies
for managing general security of data transferred via internet
We have proposed novel strategies for primate
experimentation with potential ethical, scientific, and economic
benefits. Specifically, we have proposed the establishment of
Natural Labs, as combination of indoor-outdoor structures
where to conduct cognitive neuroscience investigation in
naturalistic environments with various species of monkeys.
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Natural Labs are thought to studying various aspects of
mind, body, and behavior in the primates, where the goal is
generalization of this knowledge to understand the mechanistic
bases of human mental functions and vulnerability to disorders.
Research in primate Natural Labs may be beneficial for (1)
enhancing scientific validity, through the study of the embodied
and socially situated aspects of mental functions in primates,
in longitudinal fashion and ecological settings, (2) providing
naturalistic settings and wild-like environment for primates,
thus increasing primate welfare, (3) reducing the monkey-
human conflict in areas where monkeys are becoming pest
and allowing data collection that can be instrumental to
primate conservation.
This proposed novel strategy of primate experimentation
is of particular importance for understanding mechanisms of
human mind, in its functional and dysfunctional manifestation,
because human beings are tropical primates and have expanded
their habitat by explosive mental development (without physical
changes) in the last tens of thousands of years (Iriki et al.,
Although the realization of Natural Labs is in accordance
with current ethical framework, it subtly incentivizes an
enrichment of the current understanding of animal ethics.
Natural Labs can enrich primate welfare with a novel
perspective: primates have the potential for living and/or
interacting collaboratively with humans and exchange needs
and requirements with them. This species differences affect the
relationship we can establish with and the value we assign to
them: beyond the protection of primates according to their
capacity to experience pain, the approach of Natural Labs would
actively increase primate welfare.
Realizing Natural Labs for primate research and
implement correlated investigative practices could require the
establishment of updated ethical guidelines, which can regulate
from the one hand, the interactions between human and NHPs,
and from the other hand, rules and regulations between various
research centers, laboratories and researchers. Although the aim
of this manuscript is not to propose these guidelines but to
generate discussion, we hope that this perspective can constitute
a fruitful addition for achieving further progress in primate
experimentation and welfare.
Author contributions
AI and AT contributed to conception and design of the
study. Both authors contributed to manuscript revision, read,
and approved the submitted version.
Conflict of interest
The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could
be construed as a potential conflict of interest.
Publisher’s note
All claims expressed in this article are solely those of the
authors and do not necessarily represent those of their affiliated
organizations, or those of the publisher, the editors and the
reviewers. Any product that may be evaluated in this article, or
claim that may be made by its manufacturer, is not guaranteed
or endorsed by the publisher.
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... Today, primate research takes place in various settings that each present unique advantages and limitations in terms of methodology, translatability, animal welfare, and ethics [1,4,[10][11][12][13][14]. Research environments that most closely resemble primates' wild living conditions are considered to be best suited for evaluating their natural psychological processes [1,2,[15][16][17]. ...
... This is where primates can live in large social groups and move freely between indoor and outdoor enclosures. These more natural laboratory environments may allow for observing richer, more naturalistic behaviors while maintaining some level of experimental control [16], and reduce the expression of abnormal behaviors [36]. ...
... In 2022, the International Union for Conservation of Nature (I.U.C.N.) listed the long-tailed macaque (Macaca fascicularis) as "endangered" for the first time, in part because of their exploitation for research purposes [42]. Additionally, the growing costs of keeping primates in laboratories make alternative research settings increasingly desirable [16]. ...
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Internationally, primate research takes place in laboratories, zoos, sanctuaries, and the wild. All of these settings present unique advantages and challenges in terms of methodology, translatability, animal welfare, and ethics. In this novel commentary, we explore the scientific and ethical benefits and drawbacks of conducting non-invasive psychological research with primates in each setting. We also suggest ways to overcome some of the barriers. We argue that while there may be greater experimental control in laboratory-based research, settings that more closely mirror primates’ natural habitats are generally better suited to meet their specialized needs. More naturalistic research settings, including field studies, may also circumvent some ethical concerns associated with research in captivity, and yield more ecologically valid data.
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Estimating the pose of multiple animals is a challenging computer vision problem: frequent interactions cause occlusions and complicate the association of detected keypoints to the correct individuals, as well as having highly similar looking animals that interact more closely than in typical multi-human scenarios. To take up this challenge, we build on DeepLabCut, an open-source pose estimation toolbox, and provide high-performance animal assembly and tracking—features required for multi-animal scenarios. Furthermore, we integrate the ability to predict an animal’s identity to assist tracking (in case of occlusions). We illustrate the power of this framework with four datasets varying in complexity, which we release to serve as a benchmark for future algorithm development. DeepLabCut is extended to enable multi-animal pose estimation, animal identification and tracking, thereby enabling the analysis of social behaviors.
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In this paper, 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.
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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, 2, 3, 4, 5, 6, 7, 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.
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Human exhaled breath consists of more than 3000 volatile organic compounds, many of which are relevant biomarkers for various diseases. Although gas chromatography has been the gold standard for volatile organic compound (VOC) detection in exhaled breath, recent developments in mid-infrared (MIR) laser spectroscopy have led to the promise of compact point-of-care (POC) optical instruments enabling even single breath diagnostics. In this review, we discuss the evolution of MIR sensing technologies with a special focus on photoacoustic spectroscopy, and its application in exhaled breath biomarker detection. While mid-infrared point-of-care instrumentation promises high sensitivity and inherent molecular selectivity, the lack of standardization of the various techniques has to be overcome for translating these techniques into more widespread real-time clinical use.
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Abstract Psychiatric disorders are a prevalent global health problem, over 900 million individuals affected by a continuum of mental and substance use disorders. Due to this high prevalence, and the substantial direct and indirect societal costs, it is essential to understand the underlying mechanisms of these disorders to facilitate development of new and more effective treatments. Since the advent of recombinant DNA technologies in the early 1980s, genetically modified rodent models have significantly contributed to the genetic and molecular basis of psychiatric disorders. Despite significant advancements, many challenges remain after unsuccessful drug development based on rodent models. Recent human genetics show the polygenetic nature of mental disorders, identifying hundreds of allelic variants that confer increased risk. However, given the complexity of the brain, with many unique cell types, gene expression profiles, and developmental trajectories, proper animal models are needed more than ever to dissect genes and circuits in a cell type-specific manner to advance our understanding and treatment of psychiatric disorders. In this mini-review, we highlight current challenges and promises of using rodent models in advancing science and drug development, focusing on advanced techniques, and their applications to rodent models of psychiatric disorders.
Due to its low invasiveness and controllability, chemogenetic approaches offer a highly attractive option to modulate neuronal activity in basic research and future clinical applications. Chemogenetics have revolutionized neuroscience research by facilitating manipulations of selective brain circuits. To date, however, the large majority of these studies have been conducted in rodent models, while the wide application of chemogenetics in nonhuman primates (NHPs) is yet to occur. Still, important progress has been achieved in the use of chemogenetics in NHP studies in the last few years. Here we review the studies that have been published using chemogenetics in NHPs and discuss the current limitations of the technique to its more widespread use in NHPs and possible ways to overcome them.
This paper reviews theory of DNB (Dynamical Network Biomarkers) and its applications including both modern medicine and traditional medicine. We show that omics data such as gene/protein expression profiles can be effectively used to detect pre-disease states before critical transitions from healthy states to disease states by using the DNB theory. The DNB theory with big biological data is expected to lead to ultra-early precision and preventive medicine.
After a specific point in history, hominin evolution accelerated to a level that could not be accounted for by natural selection alone. An alternative mechanism has been proposed based on mutual interaction among neural, cognitive, and ecological niches in a positive feedback loop (triadic niche construction [TNC]). Nevertheless, the trigger events for the cognitive revolution of Homo sapiens as well as the reasons for this event being limited to a single species remain unknown. In this paper, using a multidisciplinary approach involving psychology, neurobiology, and phenomenology, we propose a shift in the mechanisms underlying TNC, from TNC-1 in hominids to TNC-2 in Homo sapiens, to answer these questions. As the hominin brain expanded during TNC-1, latent cognitive capabilities were incubated within its neural framework to be expressed with a simple rewiring among brain areas in TNC-2, a quick and inexpensive process but one that requires a unique set of preconditions to commence. This process was bootstrapped by the advanced function of “projection,” which enabled humans to recognize the “self” in a particular time and space in the world, allowing the manipulation of this world (in both physical and symbolic dimensions) again in a “positive feedback loop.” Finally, on the basis of this hypothesis, we discuss the immediate problems to be addressed in the research fields of cognitive science, archeology, anthropology, and neurobiology.
Organic electrochemical transistors (OECTs) have been widely used for monitoring electrophysiological activities by exploiting advantages such as flexibility, biocompatibility, low‐voltage operation, and high transconductance. Transconductance is a major factor that determines the sensitivity of OECT‐based sensors. In comparison with other field‐effect transistors, the transconductance of OECTs having the poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) channel layer is proportional to the channel thickness because the entire film acts as a channel. Therefore, the formation of a thick channel layer is essential for OECTs. However, it is difficult to form a thick film by spin coating. Herein, we introduce spray coating and successfully form a thick and uniform PEDOT:PSS layer (1.05 µm) by controlling the compressed air pressure and number of coating cycles. Moreover, we fabricated a high‐transconductance (7.5 mS) ultraflexible OECT with a sufficiently rapid response (2.3 kHz). This article is protected by copyright. All rights reserved.
Cynomolgus macaque (Macaca fascicularis) is currently a common animal model for biomedical research. The National Primate Research Center of Thailand, Chulalongkorn University (NPRCT-CU) translocated wild-borne macaques to reared colony for research purposes. At present, no studies focus on fungal microbiome (Mycobiome) of this macaque. The functional roles of mycobiome and fungal pathogens have not been elucidated. Thus, this study aimed to investigate and compare oral and fecal mycobiome between wild and captive macaques by using high-throughput sequencing on internal transcribed spacer 2 (ITS2) rDNA. The results showed that the mycobiome of wild macaque has greater alpha diversity. The fecal mycobiome has more limited alpha diversity than those in oral cavity. The community is mainly dominated by saprophytic yeast in Kasachstania genus which is related to aiding metabolic function in gut. The oral microbiome of most captive macaques presented the Cutaneotrichosporon suggesting the fungal transmission through skin-oral contact within the colony. The potential pathogens that would cause harmful transmission in reared colonies were not found in either group of macaques but the pathogen prevention and animal care is still important to be concerned. In conclusion, the results of gut mycobiome analysis in Thai Cynomolgus macaques provide us with the basic information of oral and fecal fungi and for monitoring macaques' health status for animal care of research use.