High-throughput electrophysiological or behavioral event triggered imaging of mouse mesoscale cortical activity
Timothy Murphy, Ph.D
Professor, Basic Neurosciences
Department of Psychiatry
The University of British Columbia
Host: Tanya Weerakkody (Huguenard Lab)
Resting state brain spontaneous activity is commonly used to map the brain at the mesoscale in a number of species. With the recent development of mice expressing new genetically encoded calcium indicator (GCaMP), cortical activity can be measured at high sensitivity and neuronal selectivity during behavior. We have developed a mouse training protocol and home-cage based imaging system in which water restricted mice are trained to self-initiate cortical imaging trials in exchange for water rewards. Up to 10 GCaMP6 transgenic female or male mice can be housed together in the automated home-cage imaging system. Mice are identified by RFID and wide-field, mesoscopic imaging of the dorsal cortex is performed to assess functional connectivity and responses to sensory stimuli as well as behaviorally-driven motifs. We have based the automated home-cage hardware on the Raspberry Pi single board computer. Using the Pi minimizes cost and maximizes the potential to scale up the automated home-cage imaging to many vivarium hosted, remote controlled cages. The system is also ideal for scenarios where handling animals can perturb results such as studies of circadian rhythms, micro-biomes, pathogens, or social interactions.
In addition to autonomous image acquisition, a new challenge is combining mesoscale imaging with multiple parallel measurements that range in spatial and temporal scales from single neuron electrophysiology to behavior. Here, we explored the relationship between mesoscale spontaneous calcium activity in cortex and single cell electrophysiological activity (spike detection) and secondly, with behavior. We make use of a rich set of cortical activity motifs that are present in spontaneous activity in anesthetized and awake animals. A mesoscale spike-triggered averaging procedure allowed the identification of motifs that are preferentially linked to individual spiking neurons by employing genetically targeted indicators of neuronal activity (GCaMP6). Thalamic neurons predicted and reported specific cycles of wide-scale cortical inhibition/excitation. In contrast, spike-triggered maps derived from single cortical neurons yielded spatio-temporal maps expected for regional cortical consensus function.
 Murphy TH, Boyd JD, Bolaños F, Vanni MF, Silasi G, Haupt D, and LeDue JM (2016) “High-throughput automated home-cage mesoscopic functional imaging of mouse cortex” Nature Communications 7:11611 doi:10.1038/ncomms11611
 Xiao D., Vanni MP., Mitelut C., Chan AW., Xie Y., Chen AC., Swindale, NV., and Murphy TH. (2017) Mapping cortical mesoscopic networks of single spiking cortical or sub-cortical neurons. eLife e19976. doi: 10.7554/eLife.19976