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A journey from speech to dance through the eld of oxytocin
Constantina Theofanopoulou
a
,
b
,
*
a
The Rockefeller University, New York, USA
b
Center for the Ballet and the Arts, New York University, New York, USA
ARTICLE INFO
Keywords:
Oxytocin
Vasotocin
Vasopressin
Speech
Language
Vocal learning
Songbirds
Dance
ABSTRACT
In this article, I am going through my scientic and personal journey using my work on oxytocin as a compass. I
recount how my scientic questions were shaped over the years, and how I studied them through the lens of
different elds ranging from linguistics and neuroscience to comparative and population genomics in a wide
range of vertebrate species. I explain how my evolutionary ndings and proposal for a universal gene nomen-
clature in the oxytocin-vasotocin ligand and receptor families have impacted relevant elds, and how my studies
in the oxytocin and vasotocin system in songbirds, humans and non-human primates have led me to now be
testing intranasal oxytocin as a candidate treatment for speech decits. I also discuss my projects on the
neurobiology of dance and where oxytocin ts in the picture of studying speech and dance in parallel. Lastly, I
briey communicate the challenges I have been facing as a woman and an international scholar in science and
academia, and my personal ways to overcome them.
1. An unusual start: from linguistics to neuroscience
Since I can remember myself, from early to middle and high school, I
have always been fascinated by what we call “language”, a word that
took many different meanings throughout my life. I remember myself
listening carefully to what my family and friends had to say, and more
importantly to how they were saying it; I was equally careful with the
words I was picking to express a thought or a feeling. As I am seeking to
understand the origins for this early inclination of mine, I recall my
grandparents, teachers and ardent literature readers, who would recite
poetry to me and ask me questions on the etymology of the words I was
using. This passion for language also stems from my parents’ poly-
glossia, which they instilled in me: I currently speak 6 languages (Greek,
English, Spanish, Italian, French, Catalan), including being a procient
reader of texts written in Ancient Greek and Latin.
I soon started to write my own prose and poetry and won my rst
important literature award at the age of 7 (Kid Fairytale Prize from
Minoas Publications), followed by an award in poetry at the age of 22
(Panhellenic Poetry Competition). Although I was fond of reading and
writing, I was also an excellent student at all the other school subjects,
including in Mathematics, Physics, and Biology, and was selected to
represent my school in the most competitive national competitions in
Mathematics (e.g., “Thales” competition). In fact, in almost all years of
middle and high school I was ending the school year with a clean 20/20
grade. This meant that it was not the grades themselves that guided my
future academic choices, but my own deep wishes and passions.
In an academic world, in Greece and worldwide, where the “hu-
manities vs. sciences” distinction reigned, I had to take a decision as to
which studies would enable me to best delve into the wonders of the
vehicle we use for communication that I so much cherished: language. I
decided to go for the School of Philosophy in Athens (National and
Kapodistrian University of Athens), and to choose the specialization
path of Philology and Linguistics. At that point, the eld of Linguistics
was at, what I came to later understand, a crucial nexus: one the one
hand, there were the theoretical linguists, who thought that to dissect
the mechanisms of language, one had to study language itself; on the
other hand, either neuroscientists or linguists turning to neuroscience
had begun to postulate that one cannot understand what language is,
unless through looking into the brain. The University of Athens was
almost exclusively driven by theoretical linguists, who exposed us to the
great lessons of Noam Chomsky, among others, and who left me fully
convinced that I had picked the right path that would lead me to un-
derstand the inner workings of language.
It was not until I saw an advertisement on the University’s walls
about applying for an Erasmus scholarship that enables undergraduate
students to study for a semester at a different European University,
including in Spain. This is where another important pillar of my life
comes in to explain my feverous willingness to take up this opportunity:
* The Rockefeller University, New York, USA.
E-mail address: ktheofanop@rockefeller.edu.
Contents lists available at ScienceDirect
Comprehensive Psychoneuroendocrinology
journal homepage: www.sciencedirect.com/journal/comprehensive-psychoneuroendocrinology
https://doi.org/10.1016/j.cpnec.2023.100193
Received 1 June 2023; Accepted 14 July 2023
Comprehensive Psychoneuroendocrinology 16 (2023) 100193
2
amenco. I had been dancing amenco since I was little, and, truly,
amenco was one of those elements in life that made (and still makes) all
the rest come together. Sometimes, I realize that my stellar grades in
school were because of amenco; I had created a personal motivation
system, where I was telling myself I would not go to my dance classes
unless I had nished my homework. Looking forward to a amenco class
had always propelled me to nish my homework in a concentrated and
effective manner. And here was in front of me my chance to marry both
my passions for Linguistics and amenco by traveling to the mecca of
amenco in the world: Seville.
What I did not know was that, back at that time, the University of
Seville, was abounded by professors who were studying and teaching
what is called “Neurolinguistics”, the eld that had come up to bring
closer together the elds of Neuroscience and Linguistics. I was
astounded to learn which brain regions light up while we are speaking
and about the brain plasticity during language learning in the rst years
of our lives. In very little time, I came to realize that unless I worked on
the brain circuitry of language, I would never be able to shed light on
how language came about and why humans speak the way they speak.
And this is how amenco led me to choose an academic destination that
would change my scientic understanding of language, and how art
initially played a role in a cascade of decisions that ended up making me
a Master’s holder of the “Cognitive Science and Language” program of
the University of Barcelona. In two years’ time, I passed from studying
the “form” of language for my undergraduate thesis [1] to deciphering
the brain white matter patterns that underlie language learning [2], and
the lateralization differences in the brain regions involved in language in
men vs. women, via Magnetic Resonance Imaging [3].
2. From humans to songbirds: from oxytocin to mesotocin
As a Doctoral graduate student, under the supervision of Cedric
Boeckx at the University of Barcelona and of Erich Jarvis at Duke Uni-
versity and during his transition to Rockefeller University, I came to
form the hypothesis that oxytocin could be playing an important role in
language production and learning in humans [4]. Oxytocin (OT) acts as
a hormone, neuromodulator or neurotransmitter that functions mainly
through the oxytocin receptor (OTR) to regulate a diverse set of
Table 1
Main biological functions of OT in vertebrates. First column: old nomenclature for OT in different lineages.
Second column: revised universal vertebrate nomenclature proposed in Refs. [8,9]. Third column: major
biological functions of OT in each lineage. Color shading: terms that fall under the same general biological
function (e.g., purple for ‘sexual behavior’ processes: courtship, pair-bonding, grooming, sperm ejaculation,
reproductive behavior, sexual behavior etc.; light green for ‘mothering’ processes: female pregnancy, uterine
contractions, egg-laying, nesting etc.). Partial reproduction with permission from the Supplementary Table 1
in Refs. [8,9].
C. Theofanopoulou
Comprehensive Psychoneuroendocrinology 16 (2023) 100193
3
biological processes, some of which include uterine contractions, milk
ejection, bond formation, copulation and orgasm, stress suppression,
thermoregulation, olfactory processing, auditory processing, and eye
contact [5–7] (Table 1).
This possible role of oxytocin in language was not part of any of my
supervisors’ research agenda; it was my own hypothesis that I brought to
the table during the rst month of my graduate studies. This is how I
came up with it: in the summer after nishing my Master’s studies, I
delved into scientic articles, books and documentaries that would
prepare me for a PhD in neuroscience, a eld in which I still had lots to
learn. My synthesis of the information I had chosen for my summer
education led me to the hypothesis that an important, possibly neces-
sary, aspect of language learning in human babies is the socially
rewarding feedback they receive from their parents or caregivers during
their speech attempts in the rst years of their lives [40]. Back then,
there was only some suggestive evidence. For example [41], exposed
infants, reared in an English-speaking environment, to Mandarin Chi-
nese, by exposing them to a) only audio recordings of Mandarin Chinese;
b) audiovisual stimuli (i.e., videos) where people were speaking in
Mandarin Chinese; or c) live-interactive learning with a Mandarin Chi-
nese speaker. They found that only the latter (c) gave rise to successful
language learning. Nonetheless, this experiment was made for
second-language learning, leaving unanswered the question of whether
the primary speech learning mechanisms rely on motivational and
rewarding mechanisms provided by social interactions.
And this is where OT comes into play. My literature exploration of
the social reward and motivation brain pathways led me to oxytocin, but
there was no one, to my knowledge, that had suggested back then a role
of oxytocin in the brain pathways of human language. I was only able to
nd relevant evidence in the auditory and vocal behaviors of non-
human animals. For example, OT and OTR knock-out infant mice were
found to emit fewer ultrasonic vocalizations when compared to wild-
type mice [42,43], while OTR-containing neurons in the mouse audi-
tory cortex were identied to both be involved in auditory processing of
pups’ ultrasonic vocalizations [28] and to be left-lateralized [44]. These
studies, along with other evidence at different levels of analysis (e.g.,
interaction of OT with key genes in gene pathways with an established
role in language, such as the FOXP2-CNTNAP2 pathway [4]) became the
backbone of my proposal to study the implications of OT in human
language.
Although up to that point I had only worked with human subjects, I
took up on the suggestion of Dr. Jarvis to rst test this hypothesis in
songbirds. Birdsong in his and others’ laboratories was being used as a
model to understand human language, and, in particular, “vocal
learning”, a core component of language. Vocal learning is the ability to
imitate complex sounds and is found to date in only a few independently
evolved species of mammals (humans, bats, cetaceans, sea lions and
elephants) and birds (songbirds, parrots and hummingbirds) [45,46].
Testing the social reward mechanisms of birdsong in zebra nches, a
songbird species that is widely used in research, meant that I would need
to immerse myself into experiments I had never run before. Thanks to a
lot of self-learning, generous help of other lab members, and guidance
from my mentors and collaborators, I managed to enter into the beau-
tiful world of songbirds.
I ran my rst behavioral experiments at Duke University, followed by
research at Rockefeller University, where Dr. Jarvis transitioned, and
Hunter College (City University of New York), the latter in the context of
our collaboration with Dr. Ofer Tchernichovski, who instilled in me his
unique curiosity for the nches’ vocal learning behavior. One of my rst
most exciting ndings was on the role of social reward in vocal learning
in zebra nches, where I showed that, when exposed to two different
types of songs in isolation vs. a socially rewarding context, male nches
end up learning the song of the socially rewarding context [47]. This was
the rst direct piece of evidence for my initial hypothesis [48] that social
reward gates vocal learning.
Up next, my plan was to test the hypothesis [48] that, in songbirds,
OT subserves these social reward mechanisms of vocal learning. This is
where an obstacle came up: I was not able to nd in the zebra nch
genome (version Taeniopygia_guttata-3.2.4) any gene that was called
“oxytocin” or, even, “oxytocin receptor”. Searches in the zebra nch
genome, and other avian genomes, based on mammalian OT and OTR
gene sequences were leading me to genes that were named as “meso-
tocin”, for the ligand, and “mesotocin receptor” or “vasotocin receptor
3” for the receptor (Table 2). The literature back then was equally per-
plexing, containing an array of different names [29,30,49].
I decided to reach out to several scientists working on the endocrine
system of avian species, and their responses on the matter were even
more bewildering. These were the most prominent explanations: a) the
avian mesotocin just shares a high sequence identity with the
mammalian oxytocin, but in reality they are two different genes, and
birds do not have oxytocin; b) the avian mesotocin and the mammalian
oxytocin are the same genes, but we are using different names because
their function/gene expression/gene sequence is different [50]. If a)
were the case, then this would mean that oxytocin either had not
evolved in the avian lineage or that it had been deleted, and that, either
way, I would not be able to study the oxytocin system in songbirds; if b)
were the case, then this would mean that scientists base gene nomen-
clature on parameters, such as gene function or sequence, that are
known to be variable across species. If the latter practice were adopted
across all genes, then we would be using a nomenclature that oftentimes
should not truly reect evolutionary relationships, but relationships
between specic metrics: e.g., mouse and human gene sequences of the
“oxytocin receptor” share a high sequence similarity, hence they are
given the same name, but human and zebra nch sequences for the same
(evolutionary orthologous) gene do not, hence the sequence of the
former is called “oxytocin receptor” and of the latter “vasotocin receptor
3”. This lack of clarity in the eld urged me to resolve rst the issue of
whether songbirds, and avian species in general, have or do not have the
gene that in mammals is called “oxytocin”.
Proposing a universal nomenclature for the oxytocin-vasotocin
ligand and receptor families.
To tackle this issue, I needed to get a good handle on comparative
genomics and phylogenetics, and on tools and methodologies that I had
little experience in. This required, once more, a lot of self-learning,
paired with the valuable help I was thankful to receive from my lab-
mates and mentors. Progressively and during my transition as a Post Doc
at Rockefeller University, I was able to advance genomic methods that
enabled me to nd out whether and which oxytocin-vasotocin (OT-VT)
ligands and receptors are present in 35 vertebrate and 4 invertebrate
species’ genomes. The reason why we included so many species in our
analysis was because, although the initial conundrum was for the rele-
vant genes in avian species, we soon realized that the rest of the verte-
brate species were also suffering from an inconsistent nomenclature
(Table 2).
My modus operandi was to compare across species not only the se-
quences of the genes of interest (through pairwise comparisons and
phylogenetics), but importantly to compare the genes surrounding these
putative genes of interest (synteny analyses). What I found after hun-
dreds of pairwise sequence identity comparisons was that often clearly
orthologous genes (e.g., gene X in rat and mouse) have a higher
sequence identity with another paralogous gene (e.g., gene X in mouse
with gene Y in rat) and not their orthologous one, and that sequence
identity is not a stable parameter on which we can base our gene
orthology identication and gene nomenclature. Unlike the instability
of gene sequences across species, I found that the gene territory (or, the
synteny), namely the genes that surround gene X in one species and the
same orthologous gene X in another is widely conserved. Using a com-
bination of different synteny analyses (i.e., in a 10-gene window, 100-
gene window, and chromosomal windows), I managed to clarify gene
orthologous and paralogous relationships across vertebrate species,
which led to a proposal of a universal vertebrate gene nomenclature for
these gene families. Considering that sequence identity comparisons (e.
C. Theofanopoulou
Comprehensive Psychoneuroendocrinology 16 (2023) 100193
4
g., with BLAST alignments [51]) have been used as the canon to reveal
orthologous and paralogous relationships so far, with this study I shifted
the focus of what denes gene orthology from what lies “inside” the gene
(sequence) to “outside” of it (synteny).
I believe this study is a great example that you can never expect
where science will take you. Sometimes, to address a question, in this
case, if OT is involved in vocal learning in songbirds, one needs to
resolve other pending questions that are on the way, in this case,
whether songbirds have OT to begin with. Although the resulting nd-
ings far exceeded the scope of this question, this study was necessary for
scientists like me to be condent on the exact system they are working
on and provided the needed evidence for my project that birds,
including songbirds, have the same orthologous OT and OTR genes that
are found in the rest of the vertebrates.
3. Impact of the unied gene nomenclature to the research
community
In the short time it has been published, our methodology and pro-
posal for a universal vertebrate gene nomenclature for the OT-VT ligand
and receptor families has been adopted in a variety of studies across
vertebrate lineages [52–55] and it has inuenced the NCBI and
ENSEMBL annotation groups in using synteny as the primary evidence
when it comes to annotate newly sequenced genomes, such as those that
I contributed to in the context of the Vertebrate Genomes Project [56].
Further, our methods for synteny analyses have worked as the founda-
tion of a subsequent project I co-coordinated on the evolution of the OT
pathway genes in both vertebrates and invertebrates [57].
Our ndings have also had an impact beyond the elds of neuro-
science and genomics; for example, they were used by structural bi-
ologists to explore the mechanisms responsible for the cellular
physiology of G protein coupled receptors [58]. Our identication of the
orthologous and paralogous gene relationships (or, of “which gene is
which”) across vertebrates provided their research with the correct
genes to work on, whose study led them to identify that cation coordi-
nation is required for both OT binding and OTR activation.
In the context of the aim of this Special Issue to debunk the myth that
OT is just a female hormone, I could say that with this work, at the very
least, we debunked the myth that OT is just a mammalian hormone. Now
we can support with evidence that OT is the same orthologous gene in all
vertebrate lineages (e.g., mammals, birds, amphibians, sh,
cyclostomes), not an “analogous” gene or an “oxytocin-like” gene, going
by different names in different species and lineages (e.g., mesotocin,
isotocin, glumitocin, valitocin, and neurophysin) (Table 2). I nd that
debunking the “female hormone” myth goes hand-in-hand with
debunking the “mammalian hormone” myth, since essentially the
functions in females with which OT has been traditionally linked are also
mammalian-specic (e.g., birth uterine contractions and lactation).
Upon reviewing the so far identied functions (Table 1) of OT across
vertebrates, it becomes tangible that OT is far from being involved in
only these mechanisms.
Our proposed unied gene nomenclature also met some pushback.
For example, some authors cite our paper in their work to support gene
orthology between the mammalian OT and the orthologous gene they
study in other vertebrates (e.g., in teleost sh [59], and waxbill [60]) but
do not adopt in their manuscript our proposed nomenclature, or use it
interchangeably with the old nomenclature [58]. According to some of
these authors’ experience that they communicated to us (e.g. Ref. [58],
their use of the traditional symbols was due to following reviewers’
suggestions to stick to the traditional nomenclature. In my experience as
well, although in 4/5 scientic studies I have published on the OT-VT
system since then [50,61], both editors and reviewers welcomed the use
of our unied gene nomenclature, in one case [62], one of the editors
would not allow the use of the new nomenclature, with arguments
ranging from gene nomenclature needing to echo gene identity to
nomenclatural changes happening over 100 years and not with a single
paper. Nonetheless, we were permitted to include in the conclusions of
the paper [62] the scientic reasons that made us propose a universal
nomenclature.
The most organized reaction to our proposal came from Ref. [63]
who argued that only minor nomenclatural changes are needed in this
gene family, and that changes in nomenclature should be based on
tradition, name stability, phylogeny, identity and gene function. One of
their main arguments was that a standardized system of nomenclature
already exists, “rst established in vertebrates 30 years ago”, although
we provided challenges for their practices with scientic evidence. In
our response [50], we provided further phylogenetic evidence for our
gene orthologies, based on analysis using high-quality genomes, and
proposed evidence-based criteria for gene nomenclature decisions
beyond the OT-VT ligand and receptor families, in the following order of
reliability: synteny, phylogenetic inference, sequence identity and gene
function. We also proposed the creation of a Universal Gene
Table 2
Previous and proposed terminology for genes encoding OT and VT ligands and receptors in vertebrates. Long (for example, VTR1A) and short (for example,
V1A) versions of the gene symbols are given. Aliases include terminology in the NCBI gene database. (Reproduced from Table 1 of [8,9] with permission).
Mammals Birds Turtles and
crocodiles
Frogs Fish Sharks Universal vertebrate
revision
Oxytocin (OXT, OT, Oxy)
Neurophysin (NPI)
Mesotocin (MT)
Mesotocin (MT,
MST)
Oxt-like
Neurophysin-1-
like
Mesotocin (MT,
MST)
Mesotocin (MT,
MST)
Mesotocin (MT)
Isotocin (IT, IST)
Glumitocin
Neurophysin
IT-1-like, IT-NP
Valitocin
Aspargtocin
Oxytocin (OT)
Arginine vasopressin (AVP, ARVP,
AVRP, Vp, Vsp)
Neurophysin II (NP2)
Lysine vasopressin
Phenypresin
Vasotocin (VT) Vasotocin (VT) Vasotocin (VT) Vasotocin (VT)
VT-NP,
avpl, vsnp
Vasotocin
(VT)
Vasotocin (VT)
OXTR, OTR VT3, MTR OXTR MesoR, OXTR ITR, OXTR, itnpr-like 2,
itr2
OXTR Oxytocin receptor (OTR)
AVPR1a, V1aR, V1A VT4, VT4R Avpr1, VasR Avpr1aa, VasR,
Avpr1ab
Vasotocin receptor 1 A
(VTR1A, V1A)
AVPR1b, V1bR, (A)VPR3, V3,
VIBR
VT2, AVT2R Vasotocin receptor 1B
(VTR1B, V1B)
VT1, AVPR2 Avpr2.2 V2C, V2bR2,
Avpr2.2, V2L
V2C, V2bR2 Vasotocin receptor 2 A
(VTR2A, V2A)
V2B, V2BR1, V2R,OTRI,
nft, avpr2
Vasotocin receptor 2B
(VTR2B, V2B)
AVPR2, V2R, VPV2R Avpr2bb, V2A(2), avpr2a
(a)
Vasotocin receptor 2C
(VTR2C, V2C)
C. Theofanopoulou
Comprehensive Psychoneuroendocrinology 16 (2023) 100193
5
Nomenclature Committee that will involve scientists working on
sequencing, assembly, annotation, phylogeny and genome evolution, as
well as on the respective lineages and genes for all life. I believe such
committee will enable all scientists to speak the same language for the
rst time in history, a language that will be evidence and
evolution-based, something that will revolutionize translation of nd-
ings across species and clinical research.
4. Using the evolution of the oxytocin-vasotocin receptors as a
lens to understand vertebrate genome evolution
One of the most interesting -and unexpected-ramications of the
2021 study was that our comparative genomic ndings led us to put
forward a scenario for the evolutionary history of the oxytocin-vasotocin
receptors (OTR-VTR) and, by extension, for vertebrate genome evolution
in general, that is different from the traditionally accepted one. Ac-
cording to the most inuential hypothesis for vertebrate genome evo-
lution, rst proposed by Ohno [64] 50 years ago, vertebrate genomes
evolved through two (or possibly three) rounds of whole genome
duplication: the rst in the origin of cephalochordates (e.g., amphioxus)
and vertebrates and additional ones within vertebrates. This hypothesis
was later reinforced with the nding of four HOX gene clusters in
mammals [65], construed as the possible results of two rounds of whole
genome duplication (2 R of WGD). Most studies since then, using
phylogenetic analyses only [66–68], or a combination of synteny and
phylogenetic analyses [69,70], have interpreted their ndings consid-
ering the 2 R hypothesis as the only evolutionary scenario a priori.
In both the original 2021 study and a follow-up study I single-
authored to further delve into this topic, I performed analyses of the
chromosomes or scaffolds containing OTR-VTR across different verte-
brate species and mapped these segments back to reconstructed karyo-
types of putative vertebrate or chordate ancestors. This kind of analysis,
that I named “ancestral analyses” in these studies, allow to identify the
location of genes, in this case the OTR-VTR genes, in the putative
chromosomes of the ancestor of all vertebrates or chordates. Tracing the
evolutionary history of a gene family back to the stem of vertebrates
uniquely sheds light to the rounds of WGD this family possibly under-
went. As I explained above, the evolutionary scenario I was expecting to
nd was that written in the textbooks, namely that the OTR-VTR un-
derwent 2 R of WGD.
Contrary to this expectation, my ndings pointed to two possible
scenarios, the one being consistent with the traditionally accepted 2 R of
WGD, with the rst occurring in the gnathostome-lamprey ancestor and
the second in the jawed vertebrate ancestor, but the other pointing to
only 1 R of WGD in the common ancestor of lampreys and gnathostomes,
followed by segmental duplications in both lineages. Combining the
data from the ancestral, synteny and phylogenetic analyses, I put for-
ward that the scenario consistent with 1 R of WGD is more parsimonious.
Although the analysis of one gene family is not able to capture the full
complexity of vertebrate genome evolution, this alternative scenario
may pave the way for vertebrate genome evolution to be seen through a
prism that is different to the one used in the past 50 years.
5. Oxytocin in vocal learning avian species
With the gene orthologies claried, I was nally able to work on the
OT system in songbirds, without ambiguities as to which system I was
working on and whether my ndings would be translatable to humans or
not. One of the rst experiments I tried included an intranasal admin-
istration of an OT antagonist in adult male zebra nches to assess
whether it would have any impact on the song they sing to females to
attract them.
Male zebra nches sing two types of song, the one being the “undi-
rected” song, which is the type of song they sing by themselves, possibly
to practice, and another, being the “directed song”, which they sing to
females [71]. These two types of song have some established differences
between them [71], including in the number of introductory notes the
nches sing before they start singing the main motif of the song, which
are signicantly more during directed singing, possibly to attract the
attention of the female. In my experiments, I found that the OT-anta-
gonist treated males had a signicant drop in the number of introductory
notes in their directed song, which made their “love song” more similar
to the undirected song they sing without a female [47]. This points to OT
being necessary for an important feature (i.e., introductory notes) of
directed zebra nch singing, which, as far as we know, serves the pur-
pose of attracting the female nches to copulate [71].
The zebra nch was not the only avian species I worked on. A pre-
sentation I gave at a conference attracted the attention of Dr. Kazuo
Okanoya (University of Tokyo and RIKEN Brain Science Institute), an
expert in the songbird eld, to pursue understanding together the role of
OT in the singing and general behavioral differences identied in two
very closely related songbird species/strains: the white-rumped munias
and the Bengalese nches. These two species have a very interesting
story: more than 250 years ago, the white-rumped munias were im-
ported and brought into captivity from China to Japan [72]. They were
initially used to foster exotic birds, and were articially selected against
aggression, which gave rise to a domesticated “version” of these species,
called Bengalese nches [73]. These domesticated Bengalese nches are
not only less aggressive and fearful; they also show different pigmen-
tation in their plumage and, importantly, sing a more complex song than
the white-rumped munias [74]. This has led scientists to hypothesize
that the higher vocal learning complexity in Bengalese nches might
have occurred as a by-product of their domestication. Since OT has been
highlighted in research focused on differences between domesticated
and wild species [75], and since my ndings in zebra nches suggested a
role of OT vocal learning, we hypothesized that it made a great candi-
date for studying the neurobiology underlying these species’ behavioral
differences.
In a study I co-led with Dr. Yasuko Tobari we compared the OT
nucleotide sequence and synthesis between the wild white-rumped
munias and the domesticated Bengalese nches [75]. We found spe-
cic nucleotide changes in the regulatory regions of OT, both within the
Bengalese nch population, and in comparison to the white-rumped
munias. Some of these changes we identied fall in transcription fac-
tor binding sites and are well conserved in vertebrates in general, or in
the avian lineage in particular, something that suggests they might be
sites that are responsible for functional effect differences in these spe-
cies. Additionally, we showed, via real-time quantitative PCR, a signif-
icantly lower OT mRNA expression in the diencephalon of the Bengalese
nches relative to munias, implying there is less hypothalamic OT
synthesis in the domesticated strain, although, puzzlingly, the expres-
sion was signicantly higher in the Bengalese nch cerebrum compared
to munias. Our brain region-specic gene expression results did not
match those reported in other domesticated species (e.g., rats and mice)
[76], where more OT production was found for the domesticated strain.
Our interpretation was that these differences from other domesticated
species might be due to different domestication pathways (laboratory vs.
pet domestication), and/or to different domestication processes in the
mammalian vs. the avian lineages.
Regardless of the specic interpretation, our ndings on differences
on the OT gene sequence and brain expression in two very closely related
species that differ in their vocal learning complexity indicates that OT
could subserve these differences. Studies that were run before [49,77] or
after ours [54,78] in zebra nches pointing to: a) the OTR being
differentially expressed in their vocal learning nuclei [49,78]; b) an
age-dependent downregulation of OT in the hypothalamic para-
ventricular nucleus during the rst days post-hatch, which are of para-
mount importance for vocal learning [77]; and c) OT mediating song
preference in juveniles [54], further highlight the relevance of our OT
ndings in the song complexity differences between these two songbird
species.
C. Theofanopoulou
Comprehensive Psychoneuroendocrinology 16 (2023) 100193
6
6. The evolution of the OTR-VTR genes in human and non-
human primate evolution
Putting all these studies together, I realized it was high time I turned
my attention back to humans to nd out whether the OT-VT system had
undergone any recent changes in humans that could speak to the
behavioral differences attested between them and other non-human
primates (e.g., chimpanzees, bonobos), including their ability for vocal
learning, which is not present in other primates [46]. Interestingly at
that time, more and more genomes of archaic humans (i.e., Neanderthals
and Denisovans) were getting sequenced and becoming available for
comparison in studies like ours [79–81].
I used the knowledge I had acquired in comparative genomic tools
[48] and, in co-leadership with Dr. Alejandro Andirk´
o, we explored
nucleotide variation in the OTR-VTR using multiple genomes of modern
humans, archaic humans and non-human primates (bonobos, chim-
panzees, macaques, among other species) [61]. We identied poly-
morphic sites with alleles (i.e., Single Nucleotide Polymorphisms) found
for the rst time in modern or archaic humans, or shared only between
modern humans and bonobos. On these sites we performed an array of
analyses (prediction, regulation, linkage disequilibrium, frequency, se-
lection and functional association analyses) that revealed that they are
located in open chromatin or transcription factor binding sites, are
active in specic brain regions, and/or show positive or balancing se-
lection signals in modern humans. Importantly, all of them were also
associated with specic social behaviors and neurodevelopmental or
neuropsychiatric disorders.
With these ndings, we were able to shed light to specic sites that
have likely been hotspots in hominin and primate evolution and could
explain several of the key differences between the species studied [61]
and refs. therein). For example, they might subserve sociality differences
between the Pan and the Homo lineage that resulted in the decreased
aggression and demographic success in the latter, or group-size differ-
ences between archaic and modern humans. The convergent sites we
found in modern humans and bonobos might be relevant to similarities
between them in social attention, tolerance and cooperation. Lastly,
based on the gene expression patterns of the OTR-VTR in brain regions in
humans that are associated with vocal learning [48], and based on our
aforementioned ndings in songbirds, it could be that the archaic and
modern human-specic variants could have a synergistic heterozygous
impact on the evolution of vocal learning in the human lineage.
7. Oxytocin as a treatment for speech decits in autism
spectrum disorders
Synthesizing all these ndings, and considering evidence in the
human literature showing that an intranasal administration of OT (IN-
OT) alleviates several aspects of impaired socialization and communi-
cation in children with autism spectrum disorders (ASD) [82], including
speech comprehension [83,84], I hypothesized that IN-OT could also be
used to improve decits in speech production. Malfunction in the OT
system has been repeatedly linked to ASD, as we thoroughly reviewed in
a book chapter [62] I co-led with Dr. Amelie Borie (Emory University),
while, interestingly, aberrant changes in the OT or OTR genotype, blood
genome methylation, and plasma levels have been found in ASD patients
in conjunction with speech production disorders [85,86].
As an Associate Research Professor, directing the Neurobiology of
Social Communication Lab at City University of New York and Rock-
efeller University, I was recently able to secure funding (Robertson
Therapeutic Development Fund from the Rockefeller University) that
will enable us to test this hypothesis in children diagnosed with ASD and
speech production decits. At this point, I am feeling that my research
comes full circle, as I am nally able to address in humans the hypothesis
I had put forward several years ago. Seen from a distance, the oxytocin
journey has so far equipped me with great experience in different elds,
including neuroscience, comparative genomics and population genetics,
whose tools have been valuable in my transition to human studies,
where I also apply my early knowledge in linguistics.
8. The neurobiology of dance … and oxytocin
In other scientic endeavors, I have also widened my research scope
to include the study of another sensorimotor behavior that serves social
communication in humans: dance [87]. Studying dance came as a
necessary ramication from studying speech: evidence from different
levels of analysis points to intriguing commonalities between vocal
learning (i.e., speech) and beat synchronization (i.e., dance) that go
beyond the fact that both behaviors rely on rhythmic motor control and
on a tight auditory to motor integration. For example, only vocal
learners (humans and parrots, in particular) have been found to be able
to synchronize their body movements to the beat of sound in music [88],
while developmental behavioral studies in human children have shown
that the development of the ability for a sustained beat perception and
synchronization predicts the development for phonological (speech)
production ability until late childhood [89]. These and other ndings
have led to the hypothesis [88,90] that vocal learning was a prerequisite
for the evolution of the ability to synchronize to a beat, a core feature of
dance.
In the projects I am currently coordinating, we are planning to un-
ravel the relationship between speech and dance in humans, at the level
of brain pathways, gene expression, gene variants, and therapy. For the
latter, we are testing the effect of a behavioral dance intervention in the
speech decits of people with Parkinson’s Disease. Thinking back of the
moment I saw the Erasmus advertisement for studying in Seville, and
amenco being one of the major drivers of my decision to pursue this
application, I can see how my life comes full circle not only through
oxytocin, but also through dance. I had never imagined it, but scientic
ndings would actually bring my two passions together: speech and
dance.
What is even more intriguing is that the OT-VT system was recently
found to be implicated in dance as well. In one experiment, partners
while dancing together were administered intranasally either OT or
placebo, and a motion tracking software was used to measure synchrony
between them as manifested in the velocity of their movements [91].
IN-OT was found to increase synchronized interpersonal movement
during dance. In another experiment, they compared the VTR1A/AV-
PR1A (vasotocin receptor 1A/arginine vasopressin receptor 1 A) be-
tween performing dancers vs. elite athletes and nondancers/nonathletes
and showed signicant differences in allele frequencies [92]. These
ndings suggest a role of OT and VT beyond speech, in the coordination
of complex sensory-motor behaviors. A combined dance and oxytocin
therapy to alleviate speech and general body movement decits might
be where I predict to nd my research in some years from now.
9. Challenges and solutions
In this scientic and personal journey, I faced varying challenges.
Some of them were specic to my trajectory, as I decided to switch elds
and continuously get immersed in new tools in different species. Other
challenges were (and still are) more systemic. Being a woman in science
and surviving in a male-dominant environment, especially as I am
progressing towards research independence, is a challenge by itself. To
me it took different shapes, from being actively belittled from male
colleagues to receiving verbal and physical advances and harassment.
Other challenges have been pertinent to my identity as an international
scholar, which include working in cultural and linguistic environments
that are different to those I grew up, paired with all the relevant legal
hassle (for example, to maintain, in the US, a VISA and medical insur-
ance) and, of course, being away from the safety net of family.
I have been progressively learning how to mentally frame and
overcome these challenges. For changing elds, I can only say I devoted
a great deal of time in self-learning, reading, trying, and failing.
C. Theofanopoulou
Comprehensive Psychoneuroendocrinology 16 (2023) 100193
7
Especially in the beginning it was very difcult to fail, but then I learnt
to see it as part of the process. In this, psychotherapy played a pivotal
role in cracking my past wide open, in giving me practice on how to
speak and how to listen. I envisage a future where psychotherapy would
be readily available at no cost to all scientists. As I mentioned in the
beginning of the article, dance (amenco) has always been there to give
me beat and pace whenever I felt I had lost it, but also to just help me
express myself and have fun. Another artistic expression that has been
life-changing is poetry. Writing a good poem gives me a feeling of
fulllment and purpose. Moving to the US prompted me to start writing
in English, and my rst publications in US-based poetry journals have
been reinvigorating. Giving back to the community is another way for
me to face my own challenges: unless we actively seek to make science
and academia a diverse and equitable place, my challenges will be faced
unaltered by the future generations. Last but not least, it has always been
of outmost help to maintain a circle of people with whom I felt I could
truly be myself, feel accepted, learn, change, listen and be listened.
Declaration of competing interest
The author has no competing interest to declare.
References
[1] Constantina Theofanopoulou, Brain asymmetry in the white matter making and
globularity, Front. Psychol. 6 (2015) 1355. http://journal.frontiersin.org/Art
icle/10.3389/fpsyg.2015.01355/abstract.
[2] Constantina Theofanopoulou, Light verbs in modern Greek, Studies in Greek
Linguistics (35) (2015) 607–631.
[3] C. Nú˜
nez, et al., A large-scale study on the effects of sex on gray matter asymmetry,
Brain Struct. Funct. 223 (1) (2018).
[4] Constantina Theofanopoulou, “Implications of oxytocin in human linguistic
cognition: from genome to phenome.”, Front. Neurosci. 10 (2016). http://journal.
frontiersin.org/Article/10.3389/fnins.2016.00271/abstract.
[5] Jan Bakos, Annamaria Srancikova, Tomas Havranek, Zuzana Bacova, Molecular
mechanisms of oxytocin signaling at the synaptic connection, Neural Plast. 2018
(2018), 4864107.
[6] H. Sophie Knobloch, Valery Grinevich, Evolution of oxytocin pathways in the brain
of vertebrates, Front. Behav. Neurosci. 8 (February) (2014) 1–13. http://journal.fr
ontiersin.org/article/10.3389/fnbeh.2014.00031/abstract.
[7] Andreas Meyer-Lindenberg, Gregor Domes, Peter Kirsch, Markus Heinrichs,
Oxytocin and vasopressin in the human brain: social neuropeptides for
translational medicine, Nat. Rev. Neurosci. 12 (9) (2011) 524–538, https://doi.
org/10.1038/nrn3044.
[8] Constantina Theofanopoulou, Reconstructing the evolutionary history of the
oxytocin and vasotocin receptor gene family: insights on whole genome
duplication scenarios, Dev. Biol. 479 (2021) 99–106. https://linkinghub.elsevier.
com/retrieve/pii/S0012160621001755.
[9] Constantina Theofanopoulou, Universal nomenclature for oxytocin–vasotocin
ligand and receptor families, Nature 592 (7856) (2021) 747–755. http://www.
nature.com/articles/s41586-020-03040-7.
[28] Bianca J. Marlin, et al., Oxytocin enables maternal behaviour by balancing cortical
inhibition, Nature 520 (7548) (2015) 499–504.
[29] James D. Klatt, James L. Goodson, Oxytocin-like receptors mediate pair bonding in
a socially monogamous songbird, Proc. Biol. Sci. 280 (1750) (2013).
[30] James L. Goodson, Laura Lindberg, Paul Johnson, Effects of central vasotocin and
mesotocin manipulations on social behavior in male and female zebra nches,
Horm. Behav. 45 (2) (2004) 136–143. http://linkinghub.elsevier.com/retrieve/pii
/S0018506X03002381.
[40] Constantina Theofanopoulou, “Self-Domestication in Homo sapiens: insights from
comparative genomics” ed. Michael klymkowsky, PLoS One 12 (10) (2017),
e0185306. https://dx.plos.org/10.1371/journal.pone.0185306. (Accessed 14
February 2022).
[41] Patricia K. Kuhl, Feng-Ming Tsao, Huei-Mei Liu, Foreign-Language experience in
infancy: effects of short-term exposure and social interaction on phonetic learning,
Proc. Natl. Acad. Sci. U. S. A. 100 (15) (2003) 9096–9101.
[42] Y. Takayanagi, et al., Pervasive social decits, but normal parturition, in oxytocin
receptor-decient mice, Proc. Natl. Acad. Sci. USA 102 (44) (2005) 16096–16101.
http://www.pnas.org/cgi/doi/10.1073/pnas.0505312102.
[43] J.T. Winslow, T.R. Insel, The social decits of the oxytocin knockout mouse,
Neuropeptides 36 (2–3) (2002) 221–229. https://linkinghub.elsevier.com/retrieve
/pii/S0143417902909091.
[44] Mariela Mitre, et al., A distributed network for social cognition enriched for
oxytocin receptors, J. Neurosci. 36 (8) (2016) 2517–2535. https://www.jneurosci.
org/lookup/doi/10.1523/JNEUROSCI.2409-15.2016.
[45] Vincent M. Janik, Peter J.B. Slater, in: “Vocal Learning in Mammals.”, 1997,
pp. 59–99. http://linkinghub.elsevier.com/retrieve/pii/S0065345408603770.
[46] Erich D. Jarvis, Learned birdsong and the neurobiology of human language, Ann.
N. Y. Acad. Sci. 1016 (1) (2004) 749–777, 10.1196/annals.1298.038.
[47] Constantina Theofanopoulou, Implications of Oxytocin in Speech, University of
Barcelona, 2019. http://hdl.handle.net/10803/666660.
[48] Constantina Theofanopoulou, Cedric Boeckx, Erich D. Jarvis, A hypothesis on a
role of oxytocin in the social mechanisms of speech and vocal learning, Proc. Biol.
Sci. 284 (1861) (2017), 20170988. https://royalsocietypublishing.org/doi/10.
1098/rspb.2017.0988. (Accessed 14 February 2022).
[49] Cary H. Leung, et al., Neural distribution of vasotocin receptor MRNA in two
species of songbird, Endocrinology 152 (12) (2011) 4865–4881. https://academic.
oup.com/endo/article-lookup/doi/10.1210/en.2011-1394.
[50] Constantina Theofanopoulou, Erich D. Jarvis, Reply to: the case for standardizing
gene nomenclature in vertebrates, Nature 614 (7948) (2023) E33–E36. https
://www.nature.com/articles/s41586-022-05634-9.
[51] W.J. Kent, BLAT—The BLAST-like alignment tool, Genome Res. 12 (4) (2002)
656–664. http://www.genome.org/cgi/doi/10.1101/gr.229202.
[52] Robert C. Froemke, Larry J. Young, Oxytocin, neural plasticity, and social
behavior, Annu. Rev. Neurosci. 44 (1) (2021) 359–381. https://www.annualre
views.org/doi/10.1146/annurev-neuro-102320-102847.
[53] Kengo Inada, et al., Plasticity of neural connections underlying oxytocin-mediated
parental behaviors of male mice, Neuron 110 (12) (2022) 2009–2023, e5, htt
ps://linkinghub.elsevier.com/retrieve/pii/S089662732200304X.
[54] Natalie R. Pilgeram, et al., Oxytocin receptor antagonism during early vocal
learning reduces song preference and imitation in zebra nches, Sci. Rep. 13 (1)
(2023) 6627. https://www.nature.com/articles/s41598-023-33340-7.
[55] Zegni Triki, Katie Daughters, K. Carsten, W. De Dreu, Oxytocin has ‘tend-and-
defend’ functionality in group conict across social vertebrates, Phil. Trans. Biol.
Sci. 377 (1851) (2022). https://royalsocietypublishing.org/doi/10.1098/rstb.
2021.0137.
[56] Arang Rhie, et al., Towards complete and error-free genome assemblies of all
vertebrate species, Nature 592 (7856) (2021) 737–746. http://www.nature.co
m/articles/s41586-021-03451-0.
[57] Alina M. Sartorius, Rokicki Jaroslav, Bettella Francesco, barth claudia, de
Lange Ann-Marie G, Haram Marit, Shadrin Alexey, et al., An evolutionary timeline
of the oxytocin signaling pathway, OSF Preprints (2023), https://doi.org/
10.31219/osf.io/42b8g.
[58] Justin G. Meyerowitz, et al., The oxytocin signaling complex reveals a molecular
switch for cation dependence, Nat. Struct. Mol. Biol. 29 (3) (2022) 274–281. https
://www.nature.com/articles/s41594-022-00728-4.
[59] Eric R. Schuppe, et al., Oxytocin-like receptor expression in evolutionarily
conserved nodes of a vocal network associated with male courtship in a teleost sh,
J. Comp. Neurol. 530 (6) (2022) 903–922. https://onlinelibrary.wiley.com/doi/
10.1002/cne.25257.
[60] Sandra Trigo, Paulo A. Silva, Gonçalo C. Cardoso, Marta C. Soares, Effects of
mesotocin manipulation on the behavior of male and female common waxbills,
Physiol. Behav. 267 (2023), 114226. https://linkinghub.elsevier.com/retrieve/pii
/S0031938423001518.
[61] Constantina Theofanopoulou, Alejandro Andirk´
o, Cedric Boeckx, Erich D. Jarvis,
Oxytocin and vasotocin receptor variation and the evolution of human prosociality,
Comprehensive Psychoneuroendocrinology 11 (2022), 100139. https://linkingh
ub.elsevier.com/retrieve/pii/S2666497622000303.
[62] Amelie M. Borie, Constantina Theofanopoulou, Elissar Andari, The promiscuity of
the oxytocin–vasopressin systems and their involvement in autism spectrum
disorder, in: Salehi Ahmad, Dick F. Swaab, Ruud M. Buijs, Felix Kreier, Paul
J. Lucassen (Eds.), The Human Hypothalamus: Neuropsychiatric Disorders, 2021,
pp. 121–140. https://linkinghub.elsevier.com/retrieve/pii/B9780128199
732000095.
[63] Fiona M. McCarthy, et al., The case for standardizing gene nomenclature in
vertebrates, Nature 614 (7948) (2023) E31–E32. https://www.nature.com/articles
/s41586-022-05633-w.
[64] Susumu Ohno, in: Evolution by Gene Duplication, Springer-Verlag, New York,
1970.
[65] K. Schughart, C. Kappen, F.H. Ruddle, Duplication of large genomic regions during
the evolution of vertebrate homeobox genes, Proc. Natl. Acad. Sci. USA 86 (18)
(1989) 7067. LP – 7071, http://www.pnas.org/content/86/18/7067.abstract.
[66] Austin L. Hughes, Phylogenies of developmentally important proteins do not
support the hypothesis of two rounds of genome duplication early in vertebrate
history, J. Mol. Evol. 48 (5) (1999) 565–576, https://doi.org/10.1007/
PL00006499.
[67] Andrew Martin, Is tetralogy true? Lack of support for the ‘one-to-four rule, Mol.
Biol. Evol. 18 (1) (2001) 89–93, https://doi.org/10.1093/oxfordjournals.molbev.
a003723.
[68] Yufeng Wang, Xun Gu, Evolutionary patterns of gene families generated in the
early stage of vertebrates, J. Mol. Evol. 51 (1) (2000) 88–96, https://doi.org/
10.1007/s002390010069.
[69] Xiaowei Song, Yezhong Tang, Yajun Wang, Genesis of the vertebrate FoxP
subfamily member genes occurred during two ancestral whole genome duplication
events, Gene 588 (2) (2016) 156–162.
[70] Seongsik Yun, et al., Prevertebrate local gene duplication facilitated expansion of
the neuropeptide GPCR superfamily, Mol. Biol. Evol. 32 (11) (2015) 2803–2817.
[71] Erich D. Jarvis, et al., For whom the bird sings, Neuron 21 (4) (1998) 775–788. htt
p://linkinghub.elsevier.com/retrieve/pii/S0896627300805942.
[72] K. Washio, Enigma of Bengalese Finches, Kindai-Bungei-sya, Tokyo, 1996.
[73] N. Taka-Tsukasa, Companion Birds, Shoka-Bo, Tokyo, 1917.
[74] Eri Honda, Kazuo Okanoya, Acoustical and syntactical comparisons between songs
of the white-backed munia (Lonchura striata) and its domesticated strain, the
bengalese nch (Lonchura striata var. Domestica), Zool. Sci. 16 (2) (1999)
319–326. http://www.bioone.org/doi/abs/10.2108/zsj.16.319.
C. Theofanopoulou
Comprehensive Psychoneuroendocrinology 16 (2023) 100193
8
[75] Yasuko Tobari, et al., Oxytocin variation and brain region-specic gene expression
in a domesticated avian species, Gene Brain Behav. 21 (2) (2022). https://onlineli
brary.wiley.com/doi/10.1111/gbb.12780.
[76] Jun Li, et al., Chromatin remodeling gene EZH2 involved in the genetic etiology of
autism in Chinese han population, Neurosci. Lett. 610 (2016) 182–186. https://li
nkinghub.elsevier.com/retrieve/pii/S0304394015302366.
[77] Alba Vicario, et al., Genoarchitecture of the extended amygdala in zebra nch, and
expression of FoxP2 in cell corridors of different genetic prole, Brain Struct.
Funct. 222 (1) (2017) 481–514. http://link.springer.com/10.1007/s00429-0
16-1229-6.
[78] Matthew T. Davis, et al., Expression of oxytocin receptors in the zebra nch brain
during vocal development, Developmental Neurobiology 82 (1) (2022) 3–15. https
://onlinelibrary.wiley.com/doi/10.1002/dneu.22851.
[79] Martin Kuhlwilm, others, Ancient gene ow from early modern humans into
eastern Neanderthals, Nature 530 (7591) (2016) 429–433, https://doi.org/
10.1038/nature16544.
[80] Matthias Meyer, others, A high-coverage genome sequence from an archaic
denisovan individual, Science 338 (6104) (2012) 222–226. http://science.science
mag.org/content/338/6104/222.
[81] Kay Prüfer, others, A high-coverage neandertal genome from vindija cave in
Croatia, Science (2017). http://science.sciencemag.org/content/early/2017/10
/04/science.aao1887.
[82] Guastella, J. Adam, et al., Intranasal oxytocin improves emotion recognition for
youth with autism spectrum disorders, Biol. Psychiatr. 67 (7) (2010) 692–694. htt
ps://linkinghub.elsevier.com/retrieve/pii/S0006322309011226.
[83] Eric Hollander, et al., Oxytocin increases retention of social cognition in autism,
Biol. Psychiatr. 61 (4) (2007) 498–503. http://linkinghub.elsevier.com/retrieve
/pii/S0006322306007293.
[84] Michaela Pfundmair, Franziska Lamprecht, M. Florentine, von Wedemeyer,
Dieter Frey, Your word is my command: oxytocin facilitates the understanding of
appeal in verbal communication, Psychoneuroendocrinology 73 (2016) 63–66. htt
ps://linkinghub.elsevier.com/retrieve/pii/S0306453016304590.
[85] Jolien Rijlaarsdam, et al., Prenatal stress exposure, oxytocin receptor gene (OXTR)
methylation, and child autistic traits: the moderating role of OXTR Rs53576
genotype, Autism Res. 10 (3) (2017) 430–438. https://onlinelibrary.wiley.com/d
oi/10.1002/aur.1681.
[86] Hong-Feng Zhang, et al., Plasma oxytocin and arginine-vasopressin levels in
children with autism spectrum disorder in China: associations with symptoms,
Neurosci. Bull. 32 (5) (2016) 423–432. http://link.springer.com/10.100
7/s12264-016-0046-5.
[87] Constantina Theofanopoulou, “Mobile brain imaging in butoh dancers: from
rehearsals to public performance.”, bioRxiv (2023), 2023.02.26.530087, http://
biorxiv.org/content/early/2023/02/26/2023.02.26.530087.abstract.
[88] Aniruddh D. Patel, John R. Iversen, Micah R. Bregman, Irena Schulz, Experimental
evidence for synchronization to a musical beat in a nonhuman animal, Curr. Biol.
19 (10) (2009) 827–830. https://linkinghub.elsevier.com/retrieve/pii/S09609822
09008902.
[89] Karli M. Nave, Joel S. Snyder, Erin E. Hannon, Sustained Musical Beat Perception
Develops into Late Childhood and Predicts Phonological Abilities.” Developmental
Psychology, 2023 getdoi.cfm?doi=10.1037/dev0001513.
[90] Jao Keehn, R. Joanne, John R. Iversen, Irena Schulz, Aniruddh D. Patel,
Spontaneity and diversity of movement to music are not uniquely human, Curr.
Biol. 29 (13) (2019) R621–R622. https://linkinghub.elsevier.com/retrieve/pii
/S0960982219306049.
[91] Liad Josef, et al., The oxytocinergic system mediates synchronized interpersonal
movement during dance, Sci. Rep. 9 (1) (2019) 1894. https://www.nature.co
m/articles/s41598-018-37141-1.
[92] Rachel Bachner-Melman, et al., “AVPR1a and SLC6A4 gene Polymorphisms are
associated with creative dance performance” ed. Jonathan int, PLoS Genet. 1 (3)
(2005) e42. https://dx.plos.org/10.1371/journal.pgen.0010042.
Further reading
[10] A.N.A. Verty, J.R. McFarlane, I.S. McGregor, P.E. Mallet, Evidence for an
interaction between CB1 cannabinoid and oxytocin receptors in food and water
intake, Neuropharmacology 47 (4) (2004) 593–603.
[11] Patrice Arthur, et al., “Relationship between gene expression and function of
uterotonic systems in the rat during gestation, uterine activation and both term and
preterm labour.”, J. Physiol. 586 (24) (2008) 6063–6076.
[12] S.S. Marroni, et al., Neuroanatomical and cellular substrates of hypergrooming
induced by microinjection of oxytocin in central nucleus of amygdala, an
experimental model of compulsive behavior, Mol. Psychiatr. 12 (12) (2007)
1103–1117.
[13] Marek Jankowski, et al., Oxytocin in cardiac ontogeny, Proc. Natl. Acad. Sci. U. S.
A. 101 (35) (2004) 13074–13079.
[14] Gareth Leng, Simone L. Meddle, Alison J. Douglas, Oxytocin and the maternal
brain, Curr. Opin. Pharmacol. 8 (6) (2008) 731–734.
[15] Thomas R. Insel, Terrence J. Hulihan, A gender-specic mechanism for pair
bonding: oxytocin and partner preference formation in monogamous voles, Behav.
Neurosci. 109 (4) (1995) 782–789.
[16] Diane M. Witt, Thomas R. Insel, Increased fos expression in oxytocin neurons
following masculine sexual behavior, J. Neuroendocrinol. 6 (1) (1994) 13–18,
10.1111/j.1365-2826.1994.tb00549.x. (Accessed 14 January 2020).
[17] Oliver J. Bosch, et al., “Brain oxytocin correlates with maternal aggression: link to
anxiety.”, J. Neurosci. 25 (29) (2005) 6807–6815.
[18] A. Larrazolo-L´
opez, et al., Vaginocervical stimulation enhances social recognition
memory in rats via oxytocin release in the olfactory bulb, Neuroscience 152 (3)
(2008) 585–593.
[19] Maria Petersson, Pawel Alster, Thomas Lundeberg, Kerstin Uvn¨
as-Moberg,
Oxytocin causes a long-term decrease of blood pressure in female and male rats,
Physiol. Behav. 60 (5) (1996) 1311–1315.
[20] S.K. Elabd, et al., Possible neuroendocrine role for oxytocin in bone remodeling,
Endocr. Regul. 41 (4) (2007) 131–141. http://www.ncbi.nlm.nih.gov/pubmed
/18257653. (Accessed 14 January 2020).
[21] Magalhaes, K.R.S. Joyce, et al., Oxytocin pretreatment decreases oxytocin-induced
myometrial contractions in pregnant rats in a concentration-dependent but not
time-dependent manner, Reprod. Sci. 16 (5) (2009) 501–508.
[22] Chiu Lung Wu, et al., Pharmacological effects of oxytocin on gastric emptying and
intestinal transit of a non-nutritive liquid meal in female rats, Naunyn-
Schmiedeberg’s Arch. Pharmacol. 367 (4) (2003) 406–413.
[23] Jun Yang, et al., Effect of oxytocin on acupuncture analgesia in the rat,
Neuropeptides 41 (5) (2007) 285–292.
[24] G.F. Jirikowski, J.D. Caldwell, C.A. Pedersen, W.E. Stumpf, Estradiol inuences
oxytocin-immunoreactive brain systems, Neuroscience 25 (1) (1988) 237–248.
[25] Nicholas H. Putnam, et al., The amphioxus genome and the evolution of the
chordate karyotype, Nature 453 (7198) (2008) 1064–1071.
[26] Michael Lukas, et al., The neuropeptide oxytocin facilitates pro-social behavior and
prevents social avoidance in rats and mice, Neuropsychopharmacology 36 (11)
(2011) 2159–2168.
[27] S. Filippi, et al., Role of oxytocin in the ejaculatory process, J. Endocrinol. Invest.
26 (3 Suppl) (2003) 82–86. http://www.ncbi.nlm.nih.gov/pubmed/12834028.
(Accessed 14 January 2020).
[31] H. Jonaidi, M.M. Oloumi, D.M. Denbow, Behavioral effects of
intracerebroventricular injection of oxytocin in birds, Physiol. Behav. 79 (4–5)
(2003) 725–729.
[32] James L. Goodson, Sara E. Schrock, Marcy A. Kingsbury, Oxytocin mechanisms of
stress response and aggression in a territorial nch, Physiol. Behav. 141 (2015)
154–163.
[33] John L. Carr, Martha Ann Messinger, George M. Patton, “ nesting behavior in three-
toed box turtles (Terrapene carolina triunguis) following oxytocin-induced
oviposition .”, Chelonian Conserv. Biol. 7 (1) (2008) 124–128.
[34] Jean-Luc, Rego Do, et al., Vasotocin and mesotocin stimulate the biosynthesis of
neurosteroids in the frog brain, J. Neurosci. 26 (25) (2006) 6749–6760.
[35] James L. Goodson, Andrew H. Bass, Forebrain peptides modulate sexually
polymorphic vocal circuitry, Nature 403 (6771) (2000) 769–772. http://www.
nature.com/articles/35001581. (Accessed 14 January 2020).
[36] James L. Goodson, Andrew K. Evans, Andrew H. Bass, Putative isotocin
distributions in sonic sh: relation to vasotocin and vocal-acoustic circuitry,
J. Comp. Neurol. 462 (1) (2003) 1–14, 10.1002/cne.10679. (Accessed 14 January
2020).
[37] Fernanda Francine Zimmermann, Vidarte Gaspary Karina, Maria Siebel Anna,
Carla Denise Bonan, Oxytocin reversed MK-801-induced social interaction and
aggression decits in zebrash, Behav. Brain Res. 311 (2016) 368–374.
[38] Caroline L. Wee, et al., Zebrash oxytocin neurons drive nocifensive behavior via
brainstem premotor targets, Nat. Neurosci. 22 (9) (2019) 1477–1492.
[39] Pai Chung Gwee, Boon Hui Tay, Sydney Brenner, Byrappa Venkatesh,
Characterization of the neurohypophysial hormone gene loci in elephant shark and
the Japanese lamprey: origin of the vertebrate neurohypophysial hormone genes,
BMC Evol. Biol. 9 (1) (2009) 1–15.
C. Theofanopoulou
