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High-probability grants
According to our matching algorithm, Andrew S. Alexander is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2017 |
Alexander, Andrew S. |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Retrosplenial Cortex Interactions With Entorhinal Cortex and the Visual Anchoring of Spatial Representations @ Boston University (Charles River Campus)
The hippocampus (HPC), medial entorhinal cortex (MEC), and retrosplenial cortex (RSC) are strongly implicated in memory, and atrophy of all three structures serves as an early indicator of Alzheimer's disease. In parallel to memory processes, these structures are important for spatial cognition and neurons within these regions exhibit spatially-specific firing. HPC place cells fire when an animal occupies an explicit location in the environment relative to distal visual landmarks. MEC neurons encode multiple forms of spatial information, including grid fields, wherein a single neuron is active at multiple, equidistant locations that span the entire environment and form a periodic grid. Critically, dysfunction of MEC spatial patterning disrupts sequential encoding in the HPC which is thought to underlie episodic memory. Robust MEC spatially-related firing is known to require visual information which is likely routed to the region via RSC. RSC forms a strong excitatory projection into the region, and like MEC, firing of RSC neurons can be rhythmic and exhibit spatial periodicity. Further, individual RSC neurons encode sensory, motor, and spatial variables that are known to modulate MEC activation. Although it is known that RSC is part of the visual processing network, little is known as to how RSC spatial representations are influenced by the arrangement of distal visual cues or how visually-related RSC activation in turn influences MEC activation. Given the functional and anatomical relationship between RSC and MEC, it is pertinent to explore their connectivity and joint neurophysiological dynamics at this time. This proposal seeks to further our understanding of systems interactions between MEC and RSC in spatial encoding. The proposed experiments will assay the influence of visual information in RSC and MEC spatial representations through the implementation of visual cue manipulations that expand or compress the relative angle between visual landmarks while rats perform a visually-guided navigation paradigm. Additionally, the proposed experiments will utilize optogenetics to specifically inhibit RSC projections into MEC to test hypotheses that RSC input is required for MEC visual sensitivity. Data collected in these experiments will be utilized to test computational modeling predictions about distortions to position estimation and MEC spatial representations following shifts to the known locations of familiar distal cues.
|
0.921 |
2021 |
Alexander, Andrew S. |
K99Activity Code Description: To support the initial phase of a Career/Research Transition award program that provides 1-2 years of mentored support for highly motivated, advanced postdoctoral research scientists. |
Retrosplenial Cortex Circuit Interactions Supporting Spatial Cognition and Memory @ Boston University (Charles River Campus)
This project proposes to investigate neurophysiological circuit mechanisms supporting spatial cognition and episodic memory. The retrosplenial cortex (RSC) is critical in these cognitive processes as RSC dysfunction is associated with spatial disorientation and learning and memory deficits, as well as Alzheimer?s disease pathology. One prominent idea is that RSC facilitates spatial transformations between coordinate systems, wherein egocentric spatial information encoded relative to the animal itself is related to allocentric spatial information encoded relative to the external world. This computation is required for navigation and episodic memory, as both require information experienced via sensory organs to be represented relative to the broader environment. RSC possesses the requisite anatomy and activity patterns to facilitate spatial transformations, but there has been no direct evidence of the computation occurring within the region. This gap at least partly arises from a general lack of knowledge regarding RSC base function; it is unknown if the region is flexibly recruited as a consequence of ongoing behavior, where functionally-defined RSC sub-populations project, or how afferent inputs contribute to known forms of spatial coding within the area. I will learn techniques for high-density extracellular recordings, in vivo neuroimaging, and projection- specific optogenetics to test the role of retrosplenial circuit dynamics in spatial transformations. First, I will provide the first characterization of spatial coding differences and task-based recruitment of distinct RSC sub-regions that have biased projections to egocentric and allocentric spatial processing streams. From these large populations of simultaneously recorded neurons, I will test for intra- and extra-regional internal network states that reflect computation of spatial transformations. Next, I will utilize in vivo imaging of large RSC populations longitudinally to examine if neurons are prewired or learn their spatial receptive fields as a function of task demands. I will utilize projection-specific imaging to test if specific spatial signals are transmitted to specific efferent targets in support of spatial transformations. Finally, I will pair the aforementioned methods for observing activity of large neuronal populations with projection-specific optogenetic circuit manipulations to test the role of different afferent inputs on different forms of RSC spatial coding. By utilizing innovative experimental approaches, these projects will provide important insights regarding the function of RSC in spatial transformations underlying spatial navigation and episodic memory. Results from these studies will establish RSC circuit mechanisms that mediate these cognitive processes in both healthy and pathological states. The scientific expertise and career/laboratory management tools that I will develop during the mentored phase of this award will be vital for my success as I transition into a faculty position and pursue my own independent research program.
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0.921 |