A central challenge in neuroscience is to decipher how cellular mechanisms are coordinated across multiple aspects of the circuits that control whole-animal behavior. We will briefly discuss how modern neuroscience can strive to meet these goals. A key challenge is to unify a top-down approach to brain, computation and behavior, as defined by David Marr and Horace Barlow, with a bottom-up approach that takes inspiration from genes and genetic models, molecules and cell biology. Both of these viewpoints have merit of course, and both find common ground and opportunity for unification at the level of brain circuits. The story behind this talk –too young to be declared a success – concerns a multi-PI NIH U-19 project titled Oxytocin Modulation of Neural Circuit Function and Behavior. My colleagues Robert Froemke (co-PI), Dayu Lin and Gyorgyi Buzsaki and I have focused our labs’ attention on the peptide modulator oxytocin, the neural circuits it affects, and its role in orchestrating mouse social behavior, critical for survival yet still incompletely understood. Oxytocin signaling proves essential for the social transmission of maternal behavior (Carcea, Froemke et al. Nature 2021) and vital for acquisition and storage of information about social rank (Osakada, Lin et al. in preparation). With some striking social behaviors as a starting point we seek clarification of “socio-spatial memory neural circuits” and their operation in disparate brain regions such as auditory cortex, hippocampal area CA2, lateral septum and VMHvl of the hypothalamus. From an evolutionary perspective, work on oxytocin addresses the general question of how neuromodulators can transform circuits by operating at a different level than fast neurotransmitters. It also contributes to a wider effort to comprehend “the molecules, cells, and circuits linking sensory information to the motor outputs of social behavior”, which Park and Insel called “the dark matter” of social neuroscience. In so doing, we cannot help but evaluate the challenges of multilevel, multi-investigator projects, how synergies can be sought and fostered, and indeed how success itself might be defined.
1. Delineate the goals of studies of brain, computation and behavior and how they can be integrated
2. Describe how neuromodulators such as oxytocin transform circuits and operate at a different level than fast neurotransmitters
3. Evaluate the synergies and challenges of multilevel, multi-investigator projects and how success could be defined