Searching for input-output connectivity streams in the various subdivisions of mouse orbitofrontal cortex

The Orbitofrontal Cortex (OFC) is critical for flexible coding and updating of stimulus value which in turn explains its role in decision making processes. Lesion studies and physiological recordings in experimental rodents are in line with subarea specific functional differences, partly comparable to previous primate studies. Emotionally relevant inputs from dopaminergic reward centers and amygdala during strong emotional reactions are also crucial in this regard. In order to explain the distinctive role of each of the OFC subregions, it is important to study the anatomical input-output architecture of these subareas specially in the mouse, which is increasingly the most widely used rodent model for physiological research at the microcircuit level. Here we present a comprehensive study of the afferents to the different sub regions of the OFC in the mouse brain using iontophoretic injections of the retrograde tracer, Fluorogold, confined to the different OFC subdivisions. Both qualitative and quantitative analysis of these inputs have been compared to brain wide axonal output projections presented in the Allen Brain Atlas: mouse connectivity. While the connectivity of the OFC with other brain areas was often bidirectional, a clear topography in inputs can also be seen from prefrontal and sensory cortices, thalamus as well as dopaminergic and serotonergic modulatory brainstem centers. The combined quantitative analysis of the efferents from Allen atlas can with our normalized densitometric inputs has the potential to reveal the existence of input-output streams emanating from the different OFC subareas, providing a potentially testable connectivity framework for their functional heterogeneity.