Exploring adult hippocampal neurogenesis using optogenetics

In the 1980s, it was widely accepted that new neurons are continuously generated in the dentate gyrus of the mammalian hippocampus. Since its acceptance, researchers have employed various techniques and behavioral paradigms to study the proliferation, differentiation, and functional role of adult-born neurons. This literature thesis aims to discuss how optogenetics is able to overcome the limitations of past techniques and provide the field with new insights into the functional role of neurogenesis. We will review the current knowledge on both adult hippocampal neurogenesis and optogenetics, present representative studies using optogenetics to investigate neurogenesis and discuss potential limitations and concerns involved in using optogenetics

Archaerhodopsin Expression in New Hippocampal Neurons

It is widely accepted that neurogenesis, the birth of new neurons, occurs in two regions in the adult mammalian brain: the subventricular zone and the dentate gyrus of the hippocampus. The hippocampus is a region of the brain widely known for its role in learning and memory. The Rhodes lab is interested in using optogenetic techniques to further observe the functional role of these new hippocampal neurons. Optogenetics is a new technique that uses light and light-sensitive protein channels to control the activity of neurons. The goal of my project is to create a genetically altered mouse model that is suitable for use in our labs optogenetics experiments. This involves incorporating archaerhodopsin, our light-sensitive protein, in the cell membranes of only new neurons. Taken under a confocal microscope, the image shown is a 40 'M-thick coronal section of the hippocampus of the genetically altered mouse brain stained with fluorescent markers for archaerhodopsin tagged with enhanced green-fluorescent protein (green), mature neurons tagged with NeuN (blue), and newly divided cells tagged with 5-bromo-2-deoxyuridine (red). The presence of sites showing an overlap of all three fluorescent markers suggests that we have successfully developed a model that integrates archaerhodopsin in new neurons. For more information about the Image of Research--Undergraduate Edition go to: http://go.library.illinois.edu/imageofresearch_ureditionOpe

Exploring Exercise- and Context-Induced Peptide Changes in Mice by Quantitative Mass Spectrometry

Recent research suggests that exercise may help facilitate abstinence from cocaine addiction, though the mechanisms are not well understood. In mice, wheel running accelerates the extinction of conditioned place preference (CPP) for cocaine, providing an animal model for evaluating potential neurological mechanisms. The objective of this study was to quantify dynamic changes in endogenous peptides in the amygdala and dentate gyrus of the hippocampus in mice exposed to a context paired with the effects of cocaine, and in response to exercise. Male C57BL/6J mice conditioned to cocaine were housed with or without running wheels for 30 days. Following a CPP test and final exposure to either a cocaine- or saline-associated context, peptides were measured in brain tissue extracts using label-free matrix-assisted laser desorption/ionization mass spectrometry (MS) and stable isotopic labeling with liquid chromatography and electrospray ionization MS. CPP in mice was significantly reduced with running, which correlated to decreased myelin basic protein derivatives in the dentate gyrus extracts, possibly reflecting increased unmyelinated granule neuron density. Exposure to a cocaine-paired context increased hemoglobin-derived peptides in runners and decreased an actin-derived peptide in sedentary animals. These results allowed us to characterize a novel set of biomarkers that are responsive to exercise in the hippocampus and in a cocaine-paired context in the amygdala