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Hippocampal network mechanisms for memory-guided behavior

记忆引导行为的海马网络机制

基本信息

批准号：
10208690
负责人：
Jill K Leutgeb
金额：
$ 36.83万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-23 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10208690
关键词：
Aging Alzheimer&apos s Disease Anatomy Animals Behavior Behavioral Brain Brain Diseases Cells Code Complex Computer Models Consumption Data Decision Making Deterioration Disease Epilepsy Episodic memory Event Frequencies Future Gender Generations Goals High Frequency Oscillation Hippocampus (Brain)Impairment Learning Lesion Location Medial Memory Memory Loss Mental Depression Modeling Neurons Neurosciences Research Patients Pattern Performance Phase Physiology Play Population Positioning Attribute Post-Traumatic Stress Disorders Process Radial Rattus Reporting Research Project Grants Retrieval Rewards Role Running Schizophrenia Services Sex Differences Short-Term Memory Site Source Stress Structure Temporal Lobe Temporal Lobe Epilepsy Testing Therapeutic Intervention Traumatic Brain Injury Update Work arm awake comorbidity dentate gyrus granule cell hippocampal subregions insight memory process neural circuit neural network novel preservation prospective relating to nervous system response spatial memory support network

项目摘要

PROJECT DESCRIPTION While the significance of brain oscillations as an indication of synchronized neuronal activity has been widely acknowledged, our understanding of how coordinated neuronal firing patterns support behavior and memory processing is only beginning to emerge. In particular, oscillations in complex memory tasks are highly dynamic with frequent transitions between predominant frequency ranges. Different brain states that are associated with behavior are characterized by a wide range of oscillatory frequencies that likely reflect distinct underlying network mechanisms to support different phases of memory. Yet, memory-guided behavior requires the uninterrupted retention and updating of task-relevant information across numerous transitions between brain states. One of the remaining key outstanding questions is thus how information is not only retained but also organized to become task-relevant throughout these transitions. To study this question, we will focus on the hippocampal dentate-CA3 network where we have recently shown that the dentate gyrus is critical for the generation of prospective coding of future correct choices by CA3 cells during sharp-wave ripples (SWRs) in a dentate-dependent working memory task. SWRs are high-frequency oscillations that are accompanied by brief increases in firing rates during which behaviorally relevant events are replayed. While our previous work determined that the prospective coding occurred during SWRs at reward locations, we propose to next determine whether the dentate inputs to CA3 are also critical for prospective coding during theta oscillations along the path to future reward locations. Given that our previous and preliminary data support the possibility that the dentate is necessary for prospective coding in CA3 during SWRs and theta states, we propose to next identify how prospective coding is coordinated across the transition between these brain states in order to support the planning of future decisions and trajectories. We predict that the neuronal representations of all available choices are played out during SWRs, while a selection of the next choice occurs during the subsequent theta state. Finally, we will establish a causal relationship between predictive neuronal firing sequences generated during high-frequency oscillations and predictive sequences in theta states by disrupting CA3 SWRs and examining subsequent behavioral choices and subsequent spike sequences in theta cycles. Taken together, these studies will allow us to describe network mechanisms in the hippocampus that dynamically interleave across brain states to support hippocampus-dependent memory. Our work will potentially also have significant implications for therapeutic intervention in diseases with gender-dependent memory comorbidities, as we will investigate potential sex differences for dentate-CA3 network computations critical for memory formation. This fills a gap in our understanding as no studies on functional network differences have been reported for this circuit despite clear evidence for sex differences in dentate-CA3 anatomy, plasticity, and response to aging, stress and diseases such as depression and epilepsy.

项目描述