Oxytocin Modulation of Neural Circuit Function & Behavior
Oxytocin is a peptide hormone synthesized and released from the hypothalamus for reproduction and maternal behavior. Recent studies have tagged oxytocin as a “trust” hormone, promising to improve social deficits in various mental disorders such as autism. Despite the enthusiasm for oxytocin, contradictory results in the efficacy of oxytocin in improving human social behaviors have been reported. Such inconsistency in literature is likely due to our poor understanding of the complexity of oxytocin action, which likely varies with behavioral state, experience, and brain structures. We believe that a better understanding of the endogenous action of oxytocin is the key to unleash the therapeutic potential of this highly evolutionary conserved neuropeptide. Advancing our understanding requires cross-level and comparative interdisciplinary studies by a group of investigators with overlapping interests and the technical capability to analyze oxytocin signaling across molecular, physiological, systems behavioral and levels.
To these ends, the proposed BRAIN Initiative Project at NYU Langone on “Oxytocin Modulation of Neural Circuit Function and Behavior” consists of four interrelated projects and four core facilities, including an Administrative Core, a Data Science Core, a Behavioral Optogenetics Core, and an Oxytocin Receptor Antibody Production Core, with the overarching goal to achieve a better understanding of the oxytocin modulation in socio-spatial behaviors, which we define as social interactions within a specific context or behavioral environment. Together these projects and cores develop new tools and use cutting-edge techniques and large-scale methods to provide an in-depth description of the neural circuitry for maternal socio-spatial behavior.
Richard Tsien, DPhil: We propose a research plan that distills oxytocin signaling in the hippocampus into its most elementary components: peptide release, receptor activation, and cell-type specific modulation of the M-current. Then, as an acid test of our understanding, we attempt to reconstruct oxytocin’s modulatory actions using our newly developed optical tools. Finally, we consider how oxytocin signaling in the hippocampus may propagate to downstream structures, ultimately influencing social behavior.
Robert Froemke, PhD: The central hypothesis is that oxytocin is absolutely necessary to initiate maternal behaviors in key areas including auditory cortex and hippocampus, but may be dispensable in experienced mothers. We will perform behavioral, optogenetic, and circuit mapping studies in adult mice to determine where and when oxytocin modulates neural circuits to enhance social information processing and subsequently improve maternal behavior.
György Buzsáki, MD, PhD: The overarching goal of our proposal is to understand how oxytocin signaling engages brain systems to support socio-spatial behavior. A central question is how oxytocin release from hypothalamic neurons affects neuronal activity in target structures and conversely, how these coordinating neurons are embedded and controlled by other neuronal circuits.
Dayu Lin, PhD: Social bonding refers to an intimate relationship formed among members of the same species. Across species, social bonding is often accompanied by increased aggressiveness toward perceived threats against the object of attachment. The neural process underlying the social bonding–induced increase in aggression remains unclear. Oxytocin plays pivotal roles in the formation of social bonds. Coincidently, the ventrolateral part of the ventromedial hypothalamus (VMHvl), a hypothalamic region indispensable for both male and female aggression, expresses a high level of oxytocin receptor and a dense cluster of oxytocin neurons are found right next to the VMHvl. Thus, we hypothesize that oxytocin may play an important role in altering the VMHvl cell responses to potential threat to increase female aggression after mother-infant bonding. This project will combine the various tools developed in Projects 1-3 to provide new insight into the neuromodulatory mechanisms in the hypothalamus that alter aggressive behavior during social bonding.
Behavioral Core: The core is led by Adam Mar, PhD, and aims to breed and maintain valuable transgenic mouse lines, shared between project labs (generally for cell-type specific manipulation of local circuits, certain receptor-expressing cells, or long-range modulatory projections). The core will also prepare these animals for project team lab use via viral injection (mostly of opsins, DREADDs, or fluorescent reporters such as GCaMP6) to greatly accelerate the studies performed by project teams, as well as aid in troubleshooting and resource/reagent validation and replication across labs. Finally, the core will work with team lab members to perform behavioral experiments. This work is facilitated by incorporating this BRAIN Initiative Behavioral Optogenetics Core into the existing Rodent Behavior Laboratory Core at NYU Langone, augmenting the capabilities of that core facility to enhance the scientific environment throughout the institution.
Antibody Core: One of the major features of this BRAIN Initiative proposal on “Oxytocin Modulation of Neural Circuit Function and Behavior” is the Oxytocin Receptor Antibody Production Research Support Core. The core is led by Moses Chao, PhD, and will continue production of oxytocin receptor antibodies, distribute these antibodies broadly, and generate monoclonal antibodies to facilitate their broader use by project labs and other investigators around the world.
Data Science Core: The Data Science Core will help ensure the management and stewardship of the datasets to be collected in our projects and by the other cores, including behavioral data (short episodes and weeks-long movies), physiological recordings (in vivo and in vitro, whole-cell, and extracellular recordings), imaging (two-photon, confocal, and fiber photometry), and gene-expression profiling. The core director is Alisa Surkis, PhD, a computational neuroscientist and data archivist, together with other core staff members Kevin Read (an informationist) and Andrea Troxel, ScD, head of the Division of Biostatistics at NYU Langone.
Administrative Core: The Administrative Core, led by Dr. Tsien, will help ensure the management, coordination, and interactions between the components of this proposal. For questions, please contact Airena Yates-Merilus, our senior program coordinator, at email@example.com. Please put in your subject line “U19 Inquiry.”