Disrupted social behavior is a core feature of compromised mental health, including anxiety and depression, and is a long-standing early diagnostic marker of disorders that emerge in later-life. Yet, we have little understanding of the ontogeny of social behavior neural circuits or how environmental perturbation at different stages of development impacts infant behavior. Using the infant rodent pup, our lab studies the specific infant neuroanatomical circuits that generate developmentally-appropriate social behavior and how these systems go awry following adversity. Our team’s work examines how ethologically-relevant social challenges, such as social hierarchy disruption and abusive caregiving during infancy, produce profound changes in brain structure and function to modify behavior. 

Lab Focus 1: Neural circuits supporting flexible social behavior in typical and perturbed development

Due to technical limitations, it has been previously challenging to functionally dissect social behavior circuits in the behaving infant.  Our lab uses state-of-the-art neuroscience techniques we have adapted for pups to dissect   functional   transitions   in   developing   amygdala   circuits   known   to   regulate   social   behavior   in   adults.  Using optogenetics   in   awake-behaving   infant   rat   pups,   we   recently   showed   that   dopaminergic   innervation   of   pup   BLA bidirectionally controls social approach behavior towards the mother and peers (Opendak et al., Neuron 2021) . Our lab assesses this  developing   circuitry   using   RNAseq, multi-unit   electrophysiology,   fiber   photometry,   and   optogenetic and chemogenetic-guided manipulation of neural ensembles and behavior in pups to directly interrogate the role of the specific brain regions and circuits in social behavior in typical and perturbed development. 

Lab Focus 2: Sensory processing of social cues promoting flexible social behavior across development

Our second major research focus has been to understand how maternal care during adversity-rearing impacts  the infant brain — an impossible experiment to conduct in humans and a novel approach in animal models.  This work demonstrated that chronic stress in the caregiver’s presence produced amygdala structural  abnormalities, heightened amygdala engagement during social behavior, and perturbed social approach  toward the caregiver (Raineki, Opendak et al., PNAS 2019). In the nest, we observed blunted cortical  processing of nurturing maternal behaviors (e.g., nursing, grooming), while cortical responses to rough handling were unaffected (Opendak et al., Nature Communications 2020).

A clear outcome that emerges from this research is the idea that social adversity perturbs neural processing of socially-relevant cues. We now aim to characterize typical and perturbed sensory processing of socially salient inputs on the level of units, ensembles and circuits across early development. Using optogenetic circuit dissection and cross-structural electrophysiological recordings, we assess age- and experience-dependent plasticity in circuits engaged in social cue processing and valence (e.g. piriform-BLA, BLA-mPFC, VTA-lateral habenula). Implementing these cutting-edge measures in pups may aid in characterizing neurophysiological plasticity supporting social processing across development and identify loci of dysfunction following adversity.

Lab Focus 3: Multi-omics identification of early biomarkers and therapeutic targets following early life stress 

While a rich literature has documented links between early adversity and later-life neuropsychiatric outcomes in humans, variability across animal models of early life adversity has made it challenging to identify early treatment targets linked with impaired behavior. Our lab compliments limited bedding and nesting models with deconstructed approaches that isolate specific features of early stress (e.g., social versus non-social context) that produce maladaptive social behavior outcomes in infants and juveniles.  Using multi-omics techniques (e.g. metabolomics, transcriptomics, proteomics, metagenomics), we have begun identifying specific biomarkers that can be targeted to prevent or ameliorate neurobehavioral impacts of early adversity.