Tag: M1 Genes and Neurons

Transgenically-targeted increase in the activity of medial entorhinal layer II neurons induces reversible field expansion and remapping of CA1 place cells

Presenter: Jasmine Dickinson

Mentor: Aldis Weible

AM Session Oral Presentation

Panel Name: M1 Genes and Neurons

Location: Oak Room

Time: 11:00am – 12:00pm

The hippocampal formation plays a critical role in memory acquisition and consolidation. Hippocampal pyramidal neurons fire in a location-specific manner. These “place” cells are thought to generate an internal representation of context dependent space. In a mouse model, we induced transgenic expression in layer II medial entorhinal cortex of a modified muscarinic G-protein coupled receptor that selectively binds clozapine-N-oxide. CNO, an otherwise inert metabolite of the antipsychotic clozapine, is a small molecule drug capable of crossing the blood-brain barrier. Binding of CNO to the receptor triggers an intracellular cascade ultimately resulting in the depolarization of the cell, and thus increased firing that lasts for several hours. We analyzed CA1 place fields before and after CNO injection. Many neurons expanded their place fields following grid cell activation, as predicted by models of grid cell to place cell transformations. However, other neurons drastically changed their firing fields (i.e. they “remapped”), while others were unchanged by CNO. All effects reversed twelve hours post injection. These effects underscore the generative nature of the hip- pocampal network, and provide empirical data to distinguish between theoretical models of place field formation.

The Search for a New Gene in Synapse Formation

Presenter: Leif Schumacher

Mentor: Tory Herman

AM Session Oral Presentations

Panel Name: M1 Genes and Neurons

Location: Oak Room

Time: 11:00am – 12:00pm

Neurons are cells that make up the sophisticated network of our brain. These cells interact with other neurons to form connecting structures called synapses. The Herman lab is interested in understanding the genes and molecular mechanisms behind this process. Neurons in vastly different species share many of the same properties. This allows us to study homologous genes in the fruit fly to gain a better understanding of our own development. I am working on a mutation, 317, that prevents the formation of normal syn- apses. I began searching for the gene responsible by crossing the 317 strains with flies carrying known and easily observable genetic markers and allowing recombination to occur between the chromosomes. Whether the progeny had my phenotype or not told me which direction on the DNA strand I should look. Every test narrowed down my search interval until it became too small to use my obvious genetic markers. Currently I am using markers only observable with a PCR technique. Once I narrow down the range to approximately 10 candidate genes, I will sequence them and compare the results to wild type flies to see which variation is responsible for the 317 phenotype. The results from my early tests showed that the gene linked to this 317 mutation is located in a segment that has no known synapse formation regulatory genes indicating that this is a new discovery. With a study of homologous genes between flies and humans, these new findings will contribute to a better understanding of how our own neurons function.

The Barcode System: A Robust In Vivo Genetic Manipulation Technique to Evaluate Essential Tumorigenic Genes

Presenter: Jesse Goldfarb

Mentor: Hui Zong

AM Session Oral Presentation

Panel Name: M1 Genes and Neurons

Location: Oak Room

Time: 11:00am – 12:00pm

The conventional method to evaluate a gene’s role in tumor formation involves targeting a gene in one population of cancer cells, grafting those cells into an organism and examining whether tumor growth is altered compared to controls. Readouts for such experiments are qualitative and observational. This method carries several scientific caveats that make it difficult to elucidate the role of genetic manipulations in tumor formation, including the inherent variation between mice and the lack of a quantitative readout. Therefore, much progress in the field of gene therapy and curative cancer treatment research had been stunted because of the lack of an ideal method. Therefore, I designed a genetic manipulation system, alongside my mentor, to effectively allow for the study of the tumorigenic role of genes believed to be involved in cancer. In essence, this system, termed ‘the barcode system’ looks at growth po- tential at the cellular level instead of the organismal level. Rather than developing two populations of mice, we create two populations of cells, and inject them into a single mouse. This removes the variation of the conventional technique and introduces an internal con- trol into the system. Further, by measuring the relative growth of each cell population via a genetic tag, a barcode, we have introduced a quantitative readout. I will address the design of this system and its early pilot testing. We found that the barcode system is a highly sensitive system that is ideal for the identification of important genes.