Memories and their emotional meaning can be the root-cause of many psychiatric diseases. For example, post-traumatic stress disorder is a quintessential `memory illness;' intrusive emotional memories constitute a core symptom that leads to intense and prolonged distress, nightmares, and flashbacks. But other psychiatric disorders, such as depression, present memory impairment: events are preferentially remembered as negative, or negative memories are preferentially accessible to recall. Humans are capable of high-level associative processes and abstract thinking. We form memories not only of objects but also most importantly of situations, feelings, and concepts or rules that are not necessarily sensory driven. Understanding how these types of thought processes are generated and organized in memories is key to the understanding of human cognition. The goal of the proposed research is to explore neurophysiological underpinning of conceptual memory formation and the emotional associations embedded within these conceptual memories. As two macaque monkeys learn a reversal learning task and abstract rules from it, we will record neuronal activity in hippocampus, rhinal cortices, and amygdala (Aim 1). Preliminary data shown in this grant support the involvement of these areas in the process of generation of conceptual memories. We will test the hypothesis that the temporal contiguity of events leads to a process of abstraction that underlies the formation of representations of conceptual memories (Aim 1). This hypothesis will be tested during concept formation by using analytic techniques to distinguish between the contributions of neural signals that represent the memory of events from signals that reflect a process of abstraction that generates a representation of a concept. Finally, we will use a chemogenetic approach (DREADDS) to silence rhinal cortices while recording in HPC and the amygdala. We will test the hypothesis that rhinal cortex input is necessary for the process of abstraction observed in HPC and amygdala (Aim 2). These mechanistic studies promise to provide opportunities for collaborative studies in the future that will connect this work to studies in humans, including patient populations, to understand interactions between conceptual memory formation and emotions.
Many psychiatric disorders are caused by maladaptive emotional behavior. In humans, emotional behavior often occurs in responses to stimuli or events that are linked to conceptual, non-sensory driven, memories. We will study the neural circuit underlying the generation of conceptual memories and associated emotional meanings, with the long-term goal of advancing the development of psychiatric treatments.
