The Effects of Inhibiting Neurons in Layer-II of the Medial Entorhinal Cortex on Hippocampal Place Cells in CA1 and CA3

Presenter: Roshan Chikarmane

Faculty Mentor: Daniel Avesar

Presentation Type: Poster 52

Primary Research Area: Science

Major: Biochemistry, Biology

The hippocampus and medial entorhinal cortex (MEC) are brain regions important for the formation and retrieval of episodic memories. Problems with hippocampus, MEC, and other related brain regions underlie neurodegenerative disorders like Alzheimer’s and Dementia (1). Therefore, it is important to understand how these brain regions work and interact. Neurons called place cells in the hippocampal CA3 and CA1 regions fire whenever an animal is in a certain location (place field), relative to landmarks in that local environment (2,3). The population level activity across all place cells represent an entire local environment, forming a comprehensive cognitive map of an environment (4). The MEC receives inputs from many regions of the cerebral cortex and projects into the hippocampus from Layer II (5). The MEC Layer II (MEC-LII) itself contains spatially responsive neurons called grid cells (6). While the behaviors of spatially responsive cells types in the MEC-LII and the hippocampus have been well established, it is unclear whether place cells utilize information from MEC-LII that contributes to their spatially selective nature. To investigate the relationship between MEC-LII activity levels and place cells, experiments will be conducted with a transgenic lines of mice that have had either HM4 or HM3 Designer Receptors Exclusively Activated by Designer Drugs (DREADD) expressed in the MECLII. Activation of DREADD receptors by administration of the pharmacologically inert ligand clozapine-n-oxide (CNO) decreases (the HM4 line) or increases (the HM3 line) neuronal activity. Using this method, we can examine how changes in MEC-LII activity impact the spatial properties of places cells in awake behaving mice as they explore their environment. This experiment will measure the transfer of information between two important brain regions that give rise to learning and memory. Understanding the brain networks involved in memory is a necessary step towards determining the causes of Alzheimer’s and Dementia.