The Perforant Path And Activity Dependent Synaptic Plasticity

Date

8-11-2021 1:55 PM

Abstract

While it is widely accepted that exercise serves as a beneficial stimulus that helps improve learning and memory, it is important to understand the molecular mechanisms that support this phenomenon. Many of these positive effects can be traced back to an increase in synaptic plasticity and dendritic spine density in the granule cells of the dentate gyrus. The main input to these Hippocampal dentate granule cells is called the entorhinal cortex. There is a strong projection from the Entorhinal cortex to the molecular layer where a neuron will synapse onto the granule cells. This projection is called the perforant pathway and is subdivided into the medial and lateral perforant pathways. The medial perforant path carries spatial information and the lateral perforant path carries contextual and time information. A recent study within the Westbrook and Goodman labs has shown how a single episode of voluntary exercise produced a functional increase in the density of spines in the outer molecular layer. Upon further testing they found that this process was mediated by Mtss1L, an early effector of synapse formation. I will use SIM1-cre mice to visualize the Medial and Lateral entorhinal cortex and their corresponding projections into the molecular layer. Not only will we be able to see which cells are involved in the circuit but using Fos-trap mice (and a retrograde virus injection) we can see how many of those related cells are active as well.

Biographies

Amirali Veshagh Biology and General Science

Amirali Veshagh is a recent graduate from Portland State University with a bachelors of science in Biology, General Science, and Liberal Studies. He is a research assistant in the Westbrook Lab, which examines the entorhinal-dentate circuit and how synapses are formed and regulated in the hippocampus. He works on figuring out exercise-induced molecular mechanisms that reshape synaptic or circuit connections and thus enhance learning and memory. His research interests include molecular biology and looking at the underlying genetic mechanisms behind different neurological disorders. Amirali believes that further biological research can elevate the level at which we can help people suffering from neurological conditions. His passion for research extends from his desire to help this patient population regain their sense of self.

Dr. Gary Westbrook, Faculty Mentor, Scientist at the Vollum Institute

Dr. Westbrook received his medical training and did graduate study in Biomedical Engineering at Case Western Reserve University. He was then an intern and resident at Mt. Auburn Hospital in Boston (Internal Medicine) and at the Washington University School of Medicine in St. Louis (Neurology). After clinical training, he spent six years in basic neuroscience research at the National Institutes of Health before moving to the Vollum Institute in 1987. He is a senior scientist at the Vollum Institute and the Rocky and Julie Dixon Professor of Neurology in the School of Medicine. He served as co-director of the Vollum Institute from 2005–2016. Dr. Westbrook has been active in the development of the Jungers Center, a joint effort between the Vollum Institute and the Department of Neurology, as well as in OHSU training activities in disease-oriented neuroscience research. He initiated the Neurobiology of Disease course in the graduate program and served as the director of the Vollum/ OHSU Neuroscience Graduate Program from 2008–2018. Dr. Westbrook has been the recipient of several research prizes, including a Jacob Javits Award and a Merit Award from the National Institutes of Health. He is a past editor-in-chief of the Journal of Neuroscience and now serves as a senior editor at eLife. He has served as a member of the Advisory Council of the National Institute of Neurological Diseases and Stroke (NINDS) and the NIH Council of Councils, which oversees the Common Fund.

Disciplines

Biology

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Aug 11th, 1:55 PM

The Perforant Path And Activity Dependent Synaptic Plasticity

While it is widely accepted that exercise serves as a beneficial stimulus that helps improve learning and memory, it is important to understand the molecular mechanisms that support this phenomenon. Many of these positive effects can be traced back to an increase in synaptic plasticity and dendritic spine density in the granule cells of the dentate gyrus. The main input to these Hippocampal dentate granule cells is called the entorhinal cortex. There is a strong projection from the Entorhinal cortex to the molecular layer where a neuron will synapse onto the granule cells. This projection is called the perforant pathway and is subdivided into the medial and lateral perforant pathways. The medial perforant path carries spatial information and the lateral perforant path carries contextual and time information. A recent study within the Westbrook and Goodman labs has shown how a single episode of voluntary exercise produced a functional increase in the density of spines in the outer molecular layer. Upon further testing they found that this process was mediated by Mtss1L, an early effector of synapse formation. I will use SIM1-cre mice to visualize the Medial and Lateral entorhinal cortex and their corresponding projections into the molecular layer. Not only will we be able to see which cells are involved in the circuit but using Fos-trap mice (and a retrograde virus injection) we can see how many of those related cells are active as well.