%0 Journal Article %A Hemant K Srivastava %A Sharba Bandyopadhyay %T Parallel lemniscal and non-lemniscal sources control auditory responses in the orbitofrontal cortex (OFC) %D 2020 %R 10.1523/ENEURO.0121-20.2020 %J eneuro %P ENEURO.0121-20.2020 %X The orbitofrontal cortex (OFC) controls flexible behavior through stimulus value updating based on stimulus outcome associations, allowing seamless navigation in dynamic sensory environments with changing contingencies. Sensory cue driven responses, primarily studied through behavior, exist in the OFC. However, OFC neurons’ sensory response properties, particularly auditory, are unknown in the mouse, a genetically tractable animal. We show that mouse OFC single neurons have unique auditory response properties showing pure oddball detection and long timescales of adaptation resulting in stimulus-history dependence. Further, we show that OFC auditory responses are shaped by two parallel sources in the auditory thalamus, lemniscal and non-lemniscal. The latter underlies a large component of the observed oddball detection and additionally controls persistent activity in the OFC through the amygdala. The deviant selectivity can serve as a signal for important changes in the auditory environment. Such signals, if coupled with persistent activity, obtained by disinhibitory control from the non-lemniscal auditory thalamus or amygdala, will allow for associations with a delayed outcome related signal, like reward prediction error, and potentially forms the basis of updating stimulus outcome associations in the OFC. Thus the baseline sensory responses allow the behavioral requirement based response modification through relevant inputs from other structures related to reward, punishment, or memory. Thus, alterations in these responses in neurological disorders can lead to behavioral deficits.Significance Statement OFC has been shown to influence the stimulus representation in the sensory cortices allowing them to adjust to the changing contingencies in the environment, but how OFC itself receives and engages with the incoming stimulus is poorly understood. The response properties of the OFC neurons from a sensory perspective, independent of behavioral state and other cognitive processes, are not known. We show that OFC robustly responds to auditory stimulation with strong context dependence and selectivity to oddball or deviant stimuli. We also show that both lemniscal and non-lemniscal pathways, both at cortical and subcortical levels, differentially contribute to auditory responses in the OFC. %U https://www.eneuro.org/content/eneuro/early/2020/08/03/ENEURO.0121-20.2020.full.pdf