PROJECT SUMMARY/ABSTRACTTemporal organization is critical to many perceptual, cognitive, and behavioral functions. These temporalabilities are adversely impacted in several mental health disorders including, but not limited to, schizophreniaand attention-deficit disorder (ADHD). However, the neurobiological underpinnings of the temporal organizationof memory and behavior remain poorly understood. Here, we will focus on the nucleus reuniens of thethalamus (RE), an understudied brain region at the nexus of communication between the hippocampus andmedial prefrontal cortex. RE is anatomically positioned to profoundly influence interactions between memoryand executive systems in the brain. Based on anatomical and theoretical considerations, we hypothesize thatRE is essential to, and RE neurons represent, sequences of events and elapsed time. However, nothing isknown about the role of RE in time and temporal contexts. In this project, we will directly test the role ofRE in time and temporal contexts in memory and behavior. We will use a broad behavioral strategy testingthree different fundamental timing tasks: AIM1, memory for sequences of events; AIM2, elapsed-time memory(scale = minutes); and AIM3, interval timing (scale = tens of seconds). One experimental approach will be totest the causal role of RE, and RE circuitry, using muscimol and state-of-the-art virally-delivered inhibitorydesigner receptors exclusively activated by designer drugs (DREADDs). In another approach, we will recordRE neural activity—neurons, ensembles, and local field potentials—using cutting-edge driveable tetrodearrays. Completion of these aims will establish foundational knowledge for understanding the role of the RE inthe temporal organization of memory and behavior. Importantly, we will integrate our findings into a unifiedtheoretical framework for RE circuitry within a medial prefrontal cortex-reuniens-hippocampus system. Whatwe learn from these studies will lead to new approaches in the study of temporal dysfunctions that occur innumerous mental health disorders.
