Several neurological and psychiatric disorders, including Alzheimer's and schizophrenia, show deficits in spatial memory tasks. Not surprisingly, the same brain areas thought to be responsible for spatial memory formation - the hippocampus and upstream entorhinal cortex - show correlated deficits. The entorhinal cortex integrates information from all the sensory modalities and then passes this information to the hippocampus, where the cognitive map is formed. Connectivity between the two regions has been implicated in both Alzheimer's and schizophrenia: the tau protein that causes Alzheimer's spreads across synapses, and errant connectivity might be responsible for a subset of the symptoms in schizophrenia. Therefore, understanding the circuitry within and between the entorhinal cortex and hippocampus is an important endeavor for basic and translational research. This project is aimed to understand the driving sensory modalities of the entorhinal cortex and hippocampus, and to understand the circuitry within and between the two structures. To do this, the firing activity of individual neurons will be recorded while a rat is exploring an environment in virtual reality. Virtual reality is necessary to precisely control the nature and availability of spatially-informative sensory cues. In this design, a change in firing properties i response to a change in a stimulus can be attributed to a strong connection between that sensory modality and the brain region of interest. Further conclusions can be made when considering the differential effects of sensory modalities on the hippocampus and entorhinal cortex. The cell types of interest are hippocampal place cells, which fire in a spatially selectiv fashion;medial entorhinal grid cells, which have spatially periodic fields;medial entorhinal border cells, which fire along the boundaries of an environment;and lateral entorhinal cells, which fire in response to objects within the environment.
The aims of this project are to distinguish the relative driving forces of distal visual, self-motion, and proximal cues on the firng of these cell types. In addition, the relationship between two distinct cell types within the media entorhinal cortex will be explored by suppressing the output of border cells and observing the effect on grid cells. Determining the contribution of distinct environmental stimuli on cells in te entorhinal cortex will provide important insights about their formation, as well as how the brain as a whole encodes spatial memories and generates the mental representation of space. Understanding the circuitry in the healthy brain will provide more traction in tackling complex psychiatirc disorders.

Public Health Relevance

Several neurological and psychiatric disorders, including Alzheimer's and schizophrenia, show deficits in both hippocampal and entorhinal structures, as well as related spatial memory function. Determining the contribution of distinct sensory stimuli on cells in the entorhinal cortex will provide important insights about their firing properties, as well as how the brain as a whole encodes spatial memories and generates the mental representation of space. Understanding the circuitry in the healthy brain will provide more traction in tackling complex psychiatric disorders, such as schizophrenia.

Agency
National Institute of Health (NIH)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31MH102969-02
Application #
8743435
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Rosemond, Erica K
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Physics
Type
Schools of Arts and Sciences
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90095