Memory is essential to cognition and is impaired in a wide range of neuropsychiatric disorders including depression, schizophrenia, autism, and dementia. However, we have only a preliminary understanding of its implementation in the brain and of its contribution to other cognitive processes. It is known that the hippocampus (HPC) is required for memory, and that hippocampal neurons store and send information about past experience to the rest of the brain in the form of synchronous, population-wide events known as sharp-wave ripples (SWRs). Evidence on multiple fronts implicates SWRs both in memory consolidation and retrieval for decision-making. Their speci?c contribution to each of these processes is unknown. It is also unknown how the rest of the brain uses these repre- sentations of the past to make decisions. In many behavioral scenarios, decisions must be made using incomplete information from memory. In these scenarios, con?dence in past knowledge (i.e., memory) is essential to optimal decision-making. However, the neural ?ring that encodes memory con?dence is largely unknown. Neurons in the orbitofrontal cortex (OFC) have been demonstrated to represent con?dence in perceptual discrimination tasks, making OFC a good candidate for the representation also of memory con?dence. The proposed work constitutes a test of the hypothesis that memory con?dence is computed in OFC and that hippocampal SWRs contribute to the expression of memory con?dence. To test this hypothesis, we will record single neuron and population activity in OFC and HPC during a working memory, con?dence-reporting task in freely behaving rats. With a bipolar stimulating electrode in the ventral hippocampal commissure, we will disrupt, on a subset of trials, SWRs that could contribute to consolidation. My speci?c aims are:
Aim 1 : To test the hypothesis that neural ?ring in OFC explicitly encodes behavioral con?dence in a working memory task.
Aim 2 : To test the hypothesis that awake SWRs immediately following experience are necessary for behavioral con?dence in a working memory task. This work is a ?rst step toward my long-term research goal to study the neural circuits underlying memory- based decision making and their dysregulation in disease. Accomplishing these aims has the potential to identify the neural basis of memory con?dence and contribute to our understanding of the HPC in memory. Furthermore, understanding the roles of HPC and OFC is of great clinical and fundamental importance, and will contribute to the understanding of neural processing required for the development of e?ective therapies for mental illness.
The ability to evaluate how con?dent we are in our memories is critical in e?ective decision-making and for an accurate sense of self, but the computation of memory con?dence and its relationship to the neural processes underlying memory are not understood. The proposed research seeks to understand the respective contributions of the orbitofrontal cortex and hippocampus, with the potential to provide a basis for the more e?ective treatment of neuropsychiatric conditions including schizophrenia, obsessive-compulsive disorder, depression, Alzheimer's dis- ease, and dementia.