Effects of in ovo electroporation on endogenous gene expression: genome-wide analysis |
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Authors: | Emma K Farley Emily Gale David Chambers Meng Li |
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Institution: | 1. Department of Biology, Georgetown University, 37th and O St NW, Washington, DC, 20057, USA 2. The Interdisciplinary Program in Neuroscience, Georgetown University, 37th and O St NW, Washington, DC, 20057, USA 3. Department of Physics, Georgetown University, 37th and O St NW, Washington, DC, 20057, USA 4. Department of Pharmacology, Georgetown University, 37th and O St NW, Washington, DC, 20057, USA 5. Neurobiology Mentorship Program, Thomas Jefferson High School for Science and Technology, 6560 Braddock Road, Alexandria, Virginia, 22312, USA
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Abstract: | Background Neurons form specific connections with targets via synapses and patterns of synaptic connectivity dictate neural function. During development, intrinsic neuronal specification and environmental factors guide both initial formation of synapses and strength of resulting connections. Once synapses form, non-evoked, spontaneous activity serves to modulate connections, strengthening some and eliminating others. Molecules that mediate intercellular communication are particularly important in synaptic refinement. Here, we characterize the influences of EphA4, a transmembrane signaling molecule, on neural connectivity. Results Using multi-electrode array analysis on in vitro cultures, we confirmed that cortical neurons mature and generate spontaneous circuit activity as cells differentiate, with activity growing both stronger and more patterned over time. When EphA4 was over-expressed in a subset of neurons in these cultures, network activity was enhanced: bursts were longer and were composed of more spikes than in control-transfected cultures. To characterize the cellular basis of this effect, dendritic spines, the major excitatory input site on neurons, were examined on transfected neurons in vitro. Strikingly, while spine number and density were similar between conditions, cortical neurons with elevated levels of EphA4 had significantly more mature spines, fewer immature spines, and elevated colocalization with a mature synaptic marker. Conclusions These results demonstrate that experimental elevation of EphA4 promotes network activity in vitro, supporting spine maturation, producing more functional synaptic pairings, and promoting more active circuitry. |
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