Aaron A Wilber

Research topics

Matched from this investigator's NIH project titles and abstracts.

• Learning and Memory
• Alzheimer's and Dementia
• Developmental Cognitive Neuroscience
• Sleep and Circadian Rhythms
• PTSD and Trauma
• Schizophrenia and Psychosis
• Depression
• Human Factors and Attention

Active NIH awards

• Neurobiological Basis of Reference Frame Coordination for Spatial Memory to Action Transformations

  5R56MH133929-02

  NIMH · FY 2025 · $516K

  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.

• Cortical-hippocampal brain dynamics during sleep following spatial learning in rodents modeling Tau and AB aggregation feature of Alzheimer's disease

  5R01AG070094-05

  NIA · FY 2025 · $363K

  PROJECT SUMMARY/ABSTRACT Alzheimer’s disease is devastating for individuals and society. Impaired learning and memory, particularly in the context of spatial navigation, is one of its early and major symptoms. Similarly, rodents recapitulating aspects of Alzheimer’s disease also exhibit early impairments in spatial navigation. A preponderance of evidence suggests abnormal cortical-hippocampal communication in humans with Alzheimer’s disease. Hippocampal-cortical interactions during sleep are thought to be critical for consolidation of newly acquired memories. However, no studies have assessed these brain dynamics during sleep in rodents modeling Tau and amyloid beta (Aβ) aggregation aspects of Alzheimer’s disease. Thus, the proposed research will explore the functionality of brain dynamics during sleep in the hippocampal-PC network in animal models of Tau and Aβ aggregation (TAβA). To do this, we will use a triple transgenic mouse where three major genes associated with familial Alzheimer’s disease are expressed leading to TAβA. This mouse model mimics plaque and tangle pathological hallmarks of the disease, with a distribution pattern similar to human patients, including synaptic changes in the limbic system. In addition, all findings will be confirmed in a transgenic rat with Aβ accumulation, plaque formation, tau accumulation, cell loss, and spatial memory impairments. Specifically, we will: 1) assess the relationship between spatial learning and memory, as well as brain dynamics during sleep, both within and across the hippocampus and cortex; 2) use a novel targeted optogenetic approach to functionally dissect the relative contributions of TAβA in the hippocampus to impaired hippocampal-cortical coupling during sleep and impaired spatial learning. 3) test the efficacy of a non-invasive visual stimulation approach, known for clearing cortical TAβA, to relieve impaired hippocampal-cortical coupling during sleep and impaired spatial learning. This project will provide insight into the normal function of a circuit that is dysfunctional in Alzheimer’s disease and allow us to probe dysfunction in this circuit that emerges in very early stages of disease progression in rodents modeling TAβA aspects of Alzheimer’s disease. This research will allow us to begin understanding changes in this network which may underlie the emergence of cognitive impairments observed in Alzheimer’s disease and begin testing the efficacy of a non-invasive treatment for reversing the functional brain abnormalities and impaired cognition.

• Cortical-hippocampal brain dynamics during sleep following spatial learning in rodents modeling Tau and AB aggregation feature of Alzheimer's disease

  3R01AG070094-05S1

  NIA · FY 2025 · $88K

  PROJECT SUMMARY/ABSTRACT Alzheimer’s disease is devastating for individuals and society. Impaired learning and memory, particularly in the context of spatial navigation, is one of its early and major symptoms. Similarly, rodents recapitulating aspects of Alzheimer’s disease also exhibit early impairments in spatial navigation. A preponderance of evidence suggests abnormal cortical-hippocampal communication in humans with Alzheimer’s disease. Hippocampal-cortical interactions during sleep are thought to be critical for consolidation of newly acquired memories. However, no studies have assessed these brain dynamics during sleep in rodents modeling Tau and amyloid beta (Aβ) aggregation aspects of Alzheimer’s disease. Thus, the proposed research will explore the functionality of brain dynamics during sleep in the hippocampal-PC network in animal models of Tau and Aβ aggregation (TAβA). To do this, we will use a triple transgenic mouse where three major genes associated with familial Alzheimer’s disease are expressed leading to TAβA. This mouse model mimics plaque and tangle pathological hallmarks of the disease, with a distribution pattern similar to human patients, including synaptic changes in the limbic system. In addition, all findings will be confirmed in a transgenic rat with Aβ accumulation, plaque formation, tau accumulation, cell loss, and spatial memory impairments. Specifically, we will: 1) assess the relationship between spatial learning and memory, as well as brain dynamics during sleep, both within and across the hippocampus and cortex; 2) use a novel targeted optogenetic approach to functionally dissect the relative contributions of TAβA in the hippocampus to impaired hippocampal-cortical coupling during sleep and impaired spatial learning. 3) test the efficacy of a non-invasive visual stimulation approach, known for clearing cortical TAβA, to relieve impaired hippocampal-cortical coupling during sleep and impaired spatial learning. This project will provide insight into the normal function of a circuit that is dysfunctional in Alzheimer’s disease and allow us to probe dysfunction in this circuit that emerges in very early stages of disease progression in rodents modeling TAβA aspects of Alzheimer’s disease. This research will allow us to begin understanding changes in this network which may underlie the emergence of cognitive impairments observed in Alzheimer’s disease and begin testing the efficacy of a non-invasive treatment for reversing the functional brain abnormalities and impaired cognition.

• Neurobiological Basis of Reference Frame Coordination for Spatial Memory to Action Transformations

  1R56MH133929-01A1

  NIMH · FY 2024 · $496K

  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.

Earlier awards

• Cortical-hippocampal brain dynamics during sleep following spatial learning in rodents modeling Tau and AB aggregation feature of Alzheimer's diseaseFY 2024 · $397K
• Targeting the orexin pathway to treat sleep disorders and improve glymphatic clearance in Alzheimer’s diseaseFY 2024 · $73K
• Cortical-hippocampal brain dynamics during sleep following spatial learning in rodents modeling Tau and AB aggregation feature of Alzheimer's diseaseFY 2023 · $429K