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Principal Investigator: Dayu Lin
Organization: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
Fiscal Year: 2024
Award: $709,362
Funding agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development
SUMMARY STATEMENT
Parental care is an innate social behavior essential for species survival. Hence, a hardwired circuit
has evolved to support its expression. However, naïve animals often show hostile behaviors
toward infants, including infanticide. These are thought to be selected to free up resources for the
perpetrator's own future offspring. Though infanticide was once considered pathological, its
prevalence—e.g., in nearly 100% of wild mice—suggests that it is a part of animals' natural
behavior repertory and could be supported by a dedicated neural circuit. We reason that hostile
behaviors toward the young under pathological conditions could be caused by deficits in both
parental and infanticidal circuits. Thus, a better understanding of both circuits is needed to
ultimately prevent child abuse. Our earlier study pinpointed estrogen receptor alpha (Esr1)-
expressing cells in the medial preoptic area (MPOAEsr1) as an essential population for maternal
care. More recently, we demonstrated Esr1 cells in the principal nucleus of the bed nucleus of
stria terminalis (BNSTprEsr1) as a critical population driving infanticide in female mice. MPOAEsr1
and BNSTprEsr1 cells antagonize each other and change excitability in opposite directions during
motherhood to support the emergence of maternal behaviors. Here, building on these findings,
we will continue our efforts to elucidate the neural circuits underlying infant-directed hostile and
caring behaviors using BNSTprEsr1 and MPOAEsr1 cells as two anchoring points. In Aim 1, we will
investigate the role of BNSTprEsr1 cells in infanticide in male mice. This is an important question
given that BNSTpr is sexually dimorphic anatomically and molecularly. We will also examine the
relationship between male BNSTprEsr1 cells activated during infant-directed behaviors and those
activated during adult-directed social behaviors using two-photon calcium imaging. In Aim 2, we
will further dissect the infanticide circuit downstream of BNSTprEsr1 cells using pathway-specific
manipulation tools. In Aim 3, we will investigate the role of medial amygdala (MeA), an upstream
region of both MPOA and BNSTpr, in young-directed behaviors. We hypothesize that MeA cells
modulate positive and negative infant-directed behaviors through their projections to the BNSTpr
and MPOA, respectively. Overall, this study promises to provide new information about the neural
underpinning of infant-directed behaviors. Such knowledge is an important step toward new
strategies to prevent child abuse in humans that can profoundly impair child health and
development.
Terms: <0-11 years old><2-photon><21+ years old><Adult><Adult Human><Adult females><Adult women><Aggression><Aggressive behavior><Alpha Cell><Amygdala><Amygdaloid Body><Amygdaloid Nucleus><Amygdaloid structure><Anatomic Sites><Anatomic structures><Anatomy><Animal Model><Animal Models and Related Studies><Animals><Automobile Driving><Bed Nucleus of Stria Terminalis><Behavior><Birth><Brain><Brain Nervous System><Calcium><Caring><Cell Body><Cell Nucleus><Cells><Child><Child Abuse><Child Development><Child Health><Child Youth><Childhood Abuse><Children (0-21)><Custom><Data><Dedications><ERalpha><ERα><ESR1><ESR1 gene><Encephalon><Estradiol Receptor alpha><Estradiol Receptor α><Estrogen Receptor 1><Estrogen Receptor alpha><Estrogen Receptor α><Female><Females in adulthood><Fiber><Future><Generations><Glucagon Cell><Glucagon Secreting Cell><Goals><Human><Image><Impairment><Infant><Infant Care><Infant and Child Development><Infanticide><Knowledge><Maternal Behavior><Medial><Mediating><Mental Health><Mental Hygiene><Mice><Mice Mammals><Modern Man><Molecular><Murine><Mus><NR3A1><Nucleus><Parturition><Pathologic><Pathway interactions><Population><Preoptic Areas><Prevalence><Psychological Health><Research><Research Resources><Resources><Role><Sex Behavior><Sexual Activity><Sexual Behavior><Site><Social Behavior><Stria Terminalis Nucleus><Structure of terminal stria nuclei of preoptic region><Testing><Time><Ventral Tegmental Area><Women in adulthood><adulthood><alpha-cell><amygdaloid nuclear complex><baby care><customs><driving><effective therapy><effective treatment><experience><fatherhood><gain of function><imaging><individual response><individualized response><infant health care><infant healthcare><kids><male><model of animal><motherhood><neural><neural circuit><neural circuitry><neural mechanism><neurocircuitry><neuromechanism><newborn care><novel><offspring><optogenetics><pathway><perpetrators><physical conditioning><physical health><preoptic region><prevent><preventing><pup><response><sex><sex activity><sex dimorphism><sexual activities><sexual dimorphism><sexually dimorphic><social role><sociobehavior><sociobehavioral><synaptic circuit><synaptic circuitry><tool><two-photon><ventral tegmentum><youngster><α-cell>