Document text
Principal Investigator: REGINA Marie SULLIVAN
Organization: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
Fiscal Year: 2024
Award: $461,238
Funding agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development
DESCRIPTION (provided by applicant): Development is a period of neurobehavioral changes requiring immature organisms to exhibit behavioral flexibility to adapt to the world. A traditional
view of development sees existing brain circuits becoming more complex to accommodate behavioral change. While certainly sometimes true, additional research suggests that developing organisms must sometimes change the neural circuitry evoked by a specific event for expression of the more mature behavior. For example, as infants transition from dependence on the mother to independence, at least some new neural circuits will be required for new adaptive behaviors to be expressed. Yet we know little about these transitions, despite recent evidence suggesting these transitions are periods of vulnerability for initiation of pathways to pathology and developmental disorders. The purpose of this proposal is to explore developmental transitions using our model of infant rat learning. Specifically, we explore a brief 5 day period in developing rat pups when they rapidly transition between attachment learning and amygdala-dependent adult-like fear learning - both supported by odor-shock pairings - which learning system is engaged is controlled by maternal presence. In Aim 1, we test the hypothesis that prefrontal cortical (PFC) subareas' development and their control by the mother contributes to pups' ability to transition between attachment learning and amygdala-dependent fear learning. We include analysis of individual PFC-amygdala brain areas but also use a novel analytical tool to assess functional connectivity - a technique similar to fMRI analysis to facilitte translational research. Aim 2 extends these networks by testing causal roles of specific network nodes. Finally, Aim 3 examines the role of dopamine, an important modulator in PFC-amygdala function in these age- and context-dependent changes in behavioral flexibility over early development. This research has health relevance in at least two areas. First, this developmental approach assesses PFC and amygdala as individual brain areas, but also with functional connectivity analysis to go beyond defining the role of a brain area to expand our understanding of its role in a larger circuit to evoke adaptive behaviors. Indeed, both dysfunction of individual
brain areas and disrupted functional connectivity have been implicated in myriad developmental disorders, including depression and ADHD. Second, this ecologically relevant approach highlights mother-infant interactions to better explain how maternal presence alters the child's behavior by expanding our understanding of how the caregiver alters brain function and neurobehavioral transitions.
Terms: <0-11 years old><21+ years old><AD/HD><ADHD><Adaptive Behaviors><Address><Adult><Adult Human><Age><Agonist><Amaze><Amygdala><Amygdaloid Body><Amygdaloid Nucleus><Amygdaloid structure><Anterior><Area><Attention deficit hyperactivity disorder><Avoidance Learning><Behavior><Behavioral><Biologic Models><Biological Models><Brain><Brain Nervous System><Brain region><Care Givers><Caregivers><Cell Communication and Signaling><Cell Signaling><Child><Child Behavior><Child Youth><Children (0-21)><Circulatory Collapse><Common Rat Strains><Complex><Data><Dependence><Development><Dopamine><Dysfunction><Electrophysiology><Electrophysiology (science)><Encephalon><Equation><Event><Exhibits><FOS gene><Fear><Fright><Functional MRI><Functional Magnetic Resonance Imaging><Functional disorder><G0S7><Generalized Growth><Growth><Health><Human><Hydroxytyramine><Immediate-Early Genes><Immunohistochemistry><Immunohistochemistry Cell/Tissue><Immunohistochemistry Staining Method><Individual><Infant><Intracellular Communication and Signaling><Learning><Lesion><Life><Measures><Mental Depression><Model System><Modeling><Modern Man><Mothers><Neonatal><Neurophysiology / Electrophysiology><Odors><Organism><Pain><Painful><Pathology><Pathway interactions><Pattern><Physiopathology><Predominantly Hyperactive-Impulsive Type Attention-Deficit Disorder><Predominantly Hyperactive-Impulsive Type Hyperactivity Disorder><Prefrontal Cortex><Preparation><Protooncogene FOS><Rat><Rats Mammals><Rattus><Receptor Protein><Research><Role><Shock><Signal Transduction><Signal Transduction Systems><Signaling><Source><Stimulus><Structure><System><Techniques><Testing><Tissue Growth><Translational Research><Translational Science><Translations><Ventral Tegmental Area><Weaning><adaptation behavior><adaptive behavior><adulthood><ages><amygdaloid nuclear complex><analytical tool><antagonism><antagonist><biological signal transduction><c fos><c-fos Gene><c-fos Proto-Oncogenes><cingulate cortex><circulatory shock><conditioned fear><conditioning><depression><developmental><developmental disease><developmental disorder><electrophysiological><fMRI><fear conditioning><flexibility><flexible><frontal cortex><frontal lobe><juvenile animal><kids><learning ability><learning achievement><learning competence><living system><neonate><neural><neural circuit><neural circuitry><neurobehavioral><neurocircuitry><new approaches><novel><novel approaches><novel strategies><novel strategy><ontogeny><pathophysiology><pathway><preference><preparations><public health relevance><pup><receptor><response><shocks><social role><synaptic circuit><synaptic circuitry><translation><translation research><translational investigation><v-FOS FBJ Murine Osteosarcoma Viral Oncogene Homolog><ventral tegmentum><young animal><youngster>