Temporal organization is critical to many perceptual, cognitive, and behavioral functions. These temporal abilities are adversely impacted in several mental health disorders including, but not limited to, schizophrenia and attention-deficit disorder (ADHD). However, the neurobiological underpinnings of the temporal organization of memory and behavior remain poorly understood. Here, we will focus on the nucleus reuniens of the thalamus (RE), an understudied brain region at the nexus of communication between the hippocampus and medial prefrontal cortex. RE is anatomically positioned to profoundly influence interactions between memory and executive systems in the brain. Based on anatomical and theoretical considerations, we hypothesize that RE is essential to, and RE neurons represent, sequences of events and elapsed time. However, nothing is known about the role of RE in time and temporal contexts. In this project, we will directly test the role of RE in time and temporal contexts in memory and behavior. We will use a broad behavioral strategy testing three 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 to test the causal role of RE, and RE circuitry, using muscimol and state-of-the-art virally-delivered inhibitory designer receptors exclusively activated by designer drugs (DREADDs). In another approach, we will record RE neural activity?neurons, ensembles, and local field potentials?using cutting-edge driveable tetrode arrays. Completion of these aims will establish foundational knowledge for understanding the role of the RE in the temporal organization of memory and behavior. Importantly, we will integrate our findings into a unified theoretical framework for RE circuitry within a medial prefrontal cortex-reuniens-hippocampus system. What we learn from these studies will lead to new approaches in the study of temporal dysfunctions that occur in numerous mental health disorders.
The focus of this research is on the neural mechanisms of the temporal organization of memory and behavior. This research is relevant to public health because it will increase knowledge about the role of a specialized thalamic nucleus in temporal perception and memory for time, two processes which are dysfunctional in numerous mental health disorders including, but not limited to, schizophrenia and attention-deficit and hyperactivity disorder (ADHD). The proposal is relevant to NIH?s mission in that it will create an innovative interdisciplinary research team to expand the knowledge base, and will establish new research avenues for several mental health disorders.
