Medial orbitofrontal cortical mechanisms underlying socially guided choice

Emory University, Atlanta GA

Investigators

Abstract

PROJECT SUMMARY Past social experiences influence our everyday choices such as what we wear and with whom we spend time. How individuals use previous social information to inform future decisions is not well-understood. My lab has developed a task, social incentivization of future choice, that pairs two familiar food reinforcers with either a social conspecific or a novel object. In a subsequent test, mice are allowed to respond for the two reinforcers, in the absence of direct social cues or reinforcement. Mice will typically respond for the reinforcer that was paired with a social experience, thus preferentially shifting choice toward reinforcers that contain social value. The medial orbitofrontal cortex (MO) is necessary for value updating and retrieval of memories that guide action – as in SIFC, when mice must associate a pellet with a social experience and later recall that information during a choice test. Brain-derived neurotrophic factor (BDNF) and its cognate receptor tropomyosin receptor kinase B (trkB) are also required for value processing, with my preliminary data revealing that Bdnf depletion in the MO obstructs SIFC performance. Collectively, the MO and BDNF/trkB signaling within the MO likely mediate SIFC, with this possibility being tested in the following aims: Aim 1: BDNF in the MO is necessary for social experience-guided choice and for learning-related dendritic spine remodeling in the BLA. This aim is supported by my preliminary data indicating that BDNF in the MO is necessary for SIFC, and published data revealing that SIFC elicits learning-associated dendritic spine remodeling in the BLA. I will first confirm that loss of BDNF in the MO indeed obstructs SIFC, as my initial data suggest. I will next determine whether MO-derived BDNF is necessary for SIFC-dependent spine remodeling in the BLA. Next, I will test the hypothesis that MO-derived BDNF and structural plasticity on BLA neurons coordinate to support SIFC. Aim 2: Local trkB in the MO, and specifically on MO-to-BLA projection neurons, supports SIFC. BDNF is subject to anterograde transport; thus, where BDNF is acting to support SIFC is unclear. I will test the hypothesis that local trkB on MO neurons is necessary for SIFC. Next, I will test the hypothesis that trkB on MO- to-BLA projection neurons is required for mice to prioritize reinforcers that were paired with social experiences. Aim 3: MO neurons form ensembles necessary for SIFC and that require trkB-mediated signaling. Neurons in the MO contribute to memory formation and retrieval in multiple contexts, raising the possibility that these neurons hold stable reward-related memory traces. I will test the hypothesis that neurons in the MO that are active during social conditioning are also necessary for mice to later favor rewards associated with social conspecifics. I will then use combinatorial viral vector strategies to test the hypothesis that trkB-mediated signaling in the MO is necessary for ensemble formation and function.