Development and application of large-scale optogenetic mapping in the mouse cortex

by Diana Heather Lim

Institution: University of British Columbia
Department: Neuroscience
Degree: PhD
Year: 2015
Record ID: 2062160
Full text PDF: http://hdl.handle.net/2429/52355


One of the major goals in neuroscience is to understand and map the connectivity of the brain. While this is no small undertaking, recent technological advances have allowed brain mapping to reach unprecedented levels. Optogenetic tools have been developed that permit selective manipulation and investigation of neural systems. Here, we have mapped in vivo intracortical activity in the mouse by combining arbitrary point optogenetic stimulation and regional voltage-sensitive dye (VSD) imaging. We first show that optogenetic photostimulation using channelrhodopsin-2 (ChR2) led to cortical maps that were similar to the maps generated with sensory stimulation. ChR2-evoked maps confirmed known intrahemispheric relationships (such as between barrel cortex and motor cortex) and known interhemispheric relationships (such as between homotopic areas). We used ChR2 point stimulation to map a number of cortical areas and used network analysis to examine relationships between cortical areas. We found asymmetrical connections between primary and secondary sensory cortex and defined the parietal association cortex as a hub node. We then applied this mapping method to map altered cortical connectivity in the early and late stages after a targeted cortical stroke (1 week post-stroke and 8 weeks post-stroke, respectively). Network analysis based on ChR2-evoked responses revealed a symmetrical bilateral sham network that was disrupted after stroke. At 1 week post-stroke, we observed wide-spread depression of ChR2-evoked activity that extended to the contralesional hemisphere. By 8 weeks post-stroke significant recovery was observed. When we considered the network as a whole, we found that scaling the ChR2-evoked activity from the stroke groups to match the sham group mean resulted in a relative distribution of responses that was indistinguishable from the sham group, suggesting network-wide down-scaling and connectional diaschisis after stroke. When connections within the peri-infarct were isolated, we did not observe equal down-scaling of responses after stroke. Our findings suggest that during recovery, most cortical areas undergo homeostatic upscaling, resulting in a relative distribution of responses that is similar to the pre-stroke (sham) network, albeit still depressed. However, recovery within the peri-infarct zone is heterogeneous and these cortical points do not follow the recovery scaling factor expected for the entire network.