Thursday, November 21, 2024
11/21/2024
PROJECT SUMMARY/ABSTRACT Guiding movements through space and establishing enduring memories based on such experiences is essential for the survival of all animals including humans. This ability is thought to require storage of memories, often in an allocentric (map-like) framework, and their conversion into a body-centered reference frame, comprised of specific locomotor actions (e.g., turning right). These frameworks must be coordinated in a fluid manner during navigation, involving both person-centered and person-independent information. Impairments in accurate navigation are often a result of spatial disorientation, which can involve a general loss of directional sense in allocentric coordinates (e.g., the goal is to the north) or deficits in determining the location of objects or goals in relation to one’s body orientation in egocentric coordinates (e.g., the goal is to my right). While the neural mechanism of these deficits may involve a distinct loss in specific spatial reference frames, impairments may also reflect a loss in transformation across reference frames, such as determining the appropriate action for an allocentric location and orientation (e.g., turning right when oriented north at a specific location). The neurobiological basis of information processing in allocentric and action reference frames is thought to involve a circuit, including the parietal cortex (PC), anterior thalamic nuclei (ATN), retrosplenial cortex (RSC), and the hippocampus (HPC). The encoding observed in ATN, HPC and PC has led to the notion that this network operates as a coordinate transformation system, enabling the coordination of these reference frames for spatial memory, such as transforming a remembered allocentric representation into the appropriate actions. While this is an attractive hypothesis, little is known about whether such coordination between reference frames takes place and, if so, what the underlying circuit dynamics are between the HPC, ATN and PC. These observations inspire our central hypothesis that the HPC-ATN-PC network is critically involved in the coordination between spatial allocentric memories and an appropriate action. Our proposal tests this hypothesis using a new task we developed in two aims directed at: 1) Determining whether the HPC-PC circuit encodes map and action information, looking for evidence of the computations underlying allocentric-egocentric transformations across the HPC-RSC-PC network, and determining if the HPC-PC circuit is critical for generating an action dependent on spatial memory (i.e., map- to-action). 2) Determining whether the ATN-PC circuit contains transformation information and is critical for the transformation from a map to action. This proposal will provide critical insight into a hippocampal- thalamo-cortical network that has received very little attention with respect to its role in spatial behavior. It represents an important step toward building a complete understanding of the neurobiological bases of dysfunctional spatial learning and memory, which occur in many psychiatric and neurodegenerative disorders such as schizophrenia, post-traumatic stress disorder, depression, and Alzheimer’s disease.
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