Orbitofrontal Cortex and Social Processing in Rodent Models

Abstract

Social processing is the reception, interpretation, and reciprocation of social information and is critical for mental health. The neural structures, circuits, and substrates regulating these complex mechanisms are not well understood. Social processing in the form of social safety learning, as measured by a rat model of social familiarity-induced anxiolysis (SoFiA), was impaired following mild blast traumatic brain injury (mbTBI). Initial findings indicated that mbTBI altered resting state network activity in the orbitofrontal cortex (OFC) and was associated with accumulation of neurotoxin marker, acrolein, in lateral prefrontal cortex (PFC) (including OFC), indicating OFC as a brain region of interest that may contribute to social processing. Measuring GABA and Glutamate-related gene expression in OFC of mbTBI or sham-exposed rat brain revealed specific elevations of metabotropic glutamate receptor type 1 and 5 (mGluR1/5) expression in mbTBI but not sham OFC. Exposure-naïve rats intracranially injected with mGluR1/5 agonist demonstrated attenuated SoFiA, and this coincided with an impairment of social recognition (SR) behavior. Additionally, inactivation of OFC by local intracranial injection of GABAA agonist, muscimol, impaired two different measures of SR in which two conspecifics, or members of the same species, one novel and one familiar, were presented and required discrimination. Novelty seeking, decision-making, memory, and gregariousness were tested in isolation to determine OFC contributions to these specific behavioral contributions to SR test performance. OFC inactivation did not impair novelty seeking, non-social decision-making, or non-social memory as measured by novel object recognition (NOR) test, or gregariousness or social decision-making as measure by social preference (SP) test. When measuring SR behavior via consecutive presentation of two different conspecifics, OFC inactivation did not impact SR. Therefore, OFC is not directly responsible for social recognition, but rather the discrimination or ability to act upon discrimination of two simultaneously present conspecifics. These data suggest a novel role for OFC in high order processing or execution of action based on social information.