Episodic memory, or the recollection of events in time and space, requires the ability to fully represent and recall context. Context-dependent cognitive processes are disrupted in a number of neuropsychiatric and neurological disorders such as schizophrenia, depression, PTSD, and Alzheimer?s disease. These disruptions are associated with changes to the parahippocampal region of the medial temporal lobe, specifically the parahippocampal cortex (PHC, human homologue of the rodent postrhinal cortex, POR) and the hippocampus (HC). The contribution of each of these areas and the mechanisms underlying the representation of these context-dependent memories is still unknown. Rebecca Burwell?s laboratory has shown that the POR, situated upstream of the HC, has neurons that respond to a particular item only when it is in a particular location (Furtak, Ahmed, and Burwell, 2012). In the HC, this type of object-location conjunctive coding emerges with the learning of an association (Komorowski, et al., 2009), and is proposed to be a signature of episodic memory. The temporal characteristics of these conjunction cells in the POR have yet to be defined, and the relationship between the conjunction cells in the POR and the HC has also not yet been described.
Aim 1 of this proposal outlines the work the candidate, Valerie Estela, has accomplished to date using in vivo electrophysiology in rats to elucidate these characteristics and relationships. In order to make direct comparisons, it is necessary to record from both regions using the same task. So far only POR cells have been analyzed from rats performing a novel location biconditional discrimination task (locBCD). Briefly, it was found that 36% of POR cells exhibited object location conjunctive coding in the locBCD task, compared with 31% in the HC in a similar task (Komorowski, et al., 2009). Additional analyses and recordings from POR and HC are underway.
Aim 2 of this proposal provides a detailed description of the experiments to be performed during the rest of the candidate?s dissertation. New technology will be used to record simultaneously in the POR and HC in order to examine the temporal characteristics of object-location conjunctive coding in the POR and HC during learning in the locBCD task. This method will allow for the within-subject comparison of timing of the emergence of these conjunctions as well as allowing for complex analysis of coupled rhythms, cross-frequency coupling, spike-field coherence, and ensemble analyses. To facilitate this analysis, the candidate will be trained in analytic and computational skills through one-on-one training, courses, workshops, and interactions with computational neuroscientists.
Aim 3 outlines a thorough plan for finding a postdoctoral mentor specializing in cutting-edge calcium imaging techniques. This proposal has been designed to combine the candidate?s expertise in in vivo electrophysiology, in vivo calcium imaging, and the analysis of these large electrophysiology and imaging datasets to prepare the candidate for an independent career where she plans to study network level analyses of the parahippocampal cortex with the goal of understanding how neural circuits encode context to guide behavior and cognition.

Public Health Relevance

Episodic memories require the ability to fully represent and recall context. This ability is disrupted in disorders such as schizophrenia, depression, PTSD, and Alzheimer?s disease, but the mechanisms underlying both the initial encoding and the subsequent disruption are unknown. Addressing this mechanistic question using in vivo methodology during my dissertation work and later in my own lab using the optical imaging techniques I acquire during my postdoctoral work will provide a multifaceted approach to elucidating these important processes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Project #
1F99NS108537-01
Application #
9613884
Study Section
Special Emphasis Panel (ZNS1)
Program Officer
Jones, Michelle
Project Start
2018-09-01
Project End
2020-08-31
Budget Start
2018-09-01
Budget End
2019-08-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Brown University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912