Long-term declarative memories in all mammalian species are formed in an area of the brain called the hippocampus. The hippocampus does this by integrating information from other regions of the brain that encode highly processed complex information about an organism's environment and its internal state. One of the final stages of processing in the hippocampus is an output structure called CA1. CA1 itself encodes memories transiently that are then relayed to other parts of the brain where memories are stored longer term. CA1 receives a large amount of input from two regions of the brain that encode different types of information. One of these, the medial entorhinal cortex, encodes information about an organism's environment. The other region, the nucleus reuniens of the thalamus, relays information from the medial prefrontal cortex concerning executive function and emotion. Because these two structures carry different types of information, they influence the formation of different types of memory in the hippocampus. The medial entorhinal cortex affects the formation of spatial memory in the hippocampus. The nucleus reuniens influences memory formation that has more of an emotional content. Subsequently, dysfunction of the nucleus reuniens input may result in pathological memory formation associated with anxiety disorders and post-traumatic stress disorders. Despite the different effects that the medial entorhinal cortex and nucleus reuniens have on hippocampal CA1 encoding, both inputs project to the same region of CA1 and produce similar population responses in CA1. However, the precise neurons and networks in hippocampal CA1 engaged by these two inputs remain poorly understood. This proposal seeks identify the hippocampal CA1 neurons activated by the medial entorhinal cortex and nucleus reuniens of the thalamus. To do this we will selectively express the optogenetic excitatory protein oChIEF-tdTomato in neurons of the medial entorhinal cortex or nucleus reuniens that project to hippocampal CA1. This will permit us to excite these inputs selectively with light stimulation and measure their impact in different subtypes of fluorescently labeled CA1 neurons in genetically-modified mice. This will allow us to identify which neurons in hippocampal CA1 are most activated by the two different inputs and what the outcome may be on the principal pyramidal cells of hippocampal CA1. The data obtained from these studies will be essential for understanding how these inputs influence the cellular and network processes involved in memory formation in hippocampal CA1. Furthermore, studies of the nucleus reuniens may help provide some insight for understanding at the cellular and network level how pathological memories may be formed in some psychiatric disorders. 0925-0001/0002 (Rev. 08/12) Page Continuation Format Page

Public Health Relevance

Brain regions encoding complex highly processed information influence memory formation through its effects on the functioning of the hippocampus. This project will investigate how two of these regions affect hippocampus function at the cellular and network level. By understanding how these regions affect hippocampal function at the cellular and network level we may gain insight into cellular and network processes in the hippocampus that are involved in the formation of pathological memories associated with anxiety disorders and post-traumatic stress disorder. 0925-0001/0002 (Rev. 08/12) Page Continuation Format Page

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Exploratory/Developmental Grants (R21)
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Neurobiology of Learning and Memory Study Section (LAM)
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Nadler, Laurie S
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Virginia Commonwealth University
Anatomy/Cell Biology
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United States
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