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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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Advisors:
Elizabeth A. Buffalo, Ph.D. (Emory University)
Steve M. Potter, Ph.D. (Georgia Institute of Technology)
Committee:
Michelle C. LaPlaca, Ph.D. (Georgia Institute of Technology)
Robert C. Liu, Ph.D. (Emory University)
Garrett B. Stanley, Ph.D. (Georgia Institute of Technology)
The entorhinal cortex (EC) in the medial temporal lobe plays a critical role in memory formation and is the site of initial morphological degradation in Alzheimer’s disease (AD). Despite the known importance of this brain region, little is known about the normal bioelectrical activity patterns of the EC in awake, behaving primates. In order to develop effective therapies for AD and other disorders affecting the EC, we must first understand its normal properties. It is recognized that neurons in the rodent EC and primate hippocampus represent space through spiking inhomogeneities. There is also a growing body of evidence supporting the idea that different cortical layers can subserve distinct cognitive functions. Using a visual memory task, we hypothesize that individual neurons in the EC will represent visual space through spiking activity and that there will be laminar differences in functional connectivity within the EC during memory formation and recognition. Finally, we will explore use of a microfluidic/microelectronic – brain tissue interfacing system as a long-term in vitro testbed for therapies targeting the EC.
In primates, one of the primary results of damage to the EC is impaired learning and memory of visuospatial relationships. We will examine neuronal activity in the EC of rhesus macaques (Macaca mulatta) performing the Visual Preferential Looking Task (VPLT). The VPLT is a free-viewing task that requires no training and capitalizes on an innate preference for novelty to assess memory for repeated images. Performance on the VPLT is sensitive to the integrity of the hippocampus and adjacent cortical regions, making it ideally suited for probing normal EC function. The spiking activity of individual neurons along with local field potentials (LFPs) will be recorded across layers of the EC with a laminar electrode array. Monkeys will be head-fixed and gaze location will be tracked with an infrared camera as they freely view the complex images. We will characterize the representation of visual space in the EC through an analysis of the relationship between gaze location and spiking. Our preliminary results demonstrate that a group of cells in the primate EC represent visual space through spiking in a regular grid. This grid may be useful for encoding changing content within a consistent coordinate system.
Because of its anatomical connectivity, the EC is well-positioned to play a critical role in hippocampal-cortical interaction. Superficial layers of the EC receive processed multisensory information and provide the main cortical input to the hippocampus, while deep layers of the EC receive output from the hippocampus and provide feedback to other cortical areas. Owing to this arrangement, the EC may show layer-specific differences in activity related to memory formation and recognition. Our preliminary results suggest that recognition is signaled by all layers of the EC in both firing rates and at LFP frequencies in the gamma-band (30-140 Hz). Superficial layers have both earlier and stronger novelty signals in terms of firing rate, but deep layers play a more nuanced role in memory formation. Despite overall greater signal strength going from deep layers to superficial layers, there was a relative increase in power transferred from superficial to deep layers during stimulus encoding, which is in alignment with the flow of visual information. However, weaker memories were formed when excessive signal power in the gamma band was transferred from superficial to deep layers at any point in time during image exploration. Weaker memories were also formed when signal power was transferred from deep to superficial layers early during image exploration, but interestingly, stronger memories were formed when there was gamma-band power transferred from deep layers at later periods of image exploration.
Disorders of the EC could be treated with electrical stimulation that emulates the desired spatiotemporal activity patterns that we have begun to characterize. Development of therapies might be accelerated by an in vitro testbed that permits electrical interfacing similar to technologies available for in vivo use (e.g. deep-brain stimulation). Current in vitro, organotypic tissue-electrode interfaces are limited to two possibilities: large sections of organotypic brain tissue sustained for a few hours with perfusion or thin brain slices cultured for potentially long periods of time. Both approaches are useful for understanding function, but have proven limited as development platforms for clinically-viable brain-machine interfaces. We aim to develop a device to provide interstitial perfusion of large sections of brain tissue on a multi-electrode array (MEA). Such a device will permit testing of electrical stimulation therapies over long periods of time using tissue that is more in vivo-like, in terms of the number of preserved cells and cellular connections, than is currently possible.
