By Adam Eggbrecht
In the Optical Radiology Laboratory at Washington University School of Medicine in St. Louis, Joe Culver and his lab have been expanding applications of their optical imaging systems in mice and in humans.
In a recent publication in Cerebral Cortex, Adam Bauer et al., combined optogenetics with optical intrinsic signal (OIS) imaging in mice to create an efficient, optogenetic effective connectivity mapping technology. Patterns of effective connectivity using these methods were compared against zero-lag correlation-based functional connectivity maps of hemoglobin in awake transgenic mice. Bauer et al., showed that the optogenetic-driven effective connectivity patterns had higher spatial specificity than more traditional functional connectivity maps based on hemoglobin and that the effective connectivity maps more closely resembled the spatial topology of axonal project connectivity established at the Allen Institute. The ‘infraslow activity’ (ISA) generally used in traditional functional connectivity studies was further leveraged by Kraft et al., again with wide field optical intrinsic signaling and monocular or binocular visual deprivation in mice to examine the effects of visual experience during critical periods of development on functional connections within and between resting state networks. The authors found network level effects that were markedly attenuated in genetically altered mice that had no Arc gene, known to be essential for activity-dependent synaptic plasticity. The results highlight the importance of critical periods during development are strongly moderated by Arc-dependent mechanisms.
Patrick Wright, who recently graduated from Joe Culver’s lab to take up a postdoctoral position with Dr. Alan Koretsky at the National Institute of Neurological Disorders and Stroke (NINDS), also utilized genetically modified mice to investigate the functional connectivity structure of cortical calcium dynamics in anesthetized and awake mice. In this paper, Dr. Wright et al. showed that the calcium dynamics of GCAMP6 mice facilitated mapping of functional connectivity networks much more efficiently by utilizing a faster frequency band (0.4-4.0 Hz) that than typically used in hemodynamic studies (0.009-0.08 Hz). In a separate paper, also out this last year, Dr. Wright et al. showed significant alterations in functional connectivity in a mouse model of optic neuritis, often an early manifestation of immune-related central nervous system demyelination in multiple sclerosis.
Another recent graduate of Joe’s lab, Dr. Matt Reisman, has expanded the toolbox for imaging brain function in mice to include non-invasive structured illumination diffuse optical tomography.
Other ongoing work in the Culver lab includes applying OIS imaging to mouse models of glioma, anesthesia, sleep, and a further expansion of the SI-DOT mouse imaging system to that of a multi-camera multi-view system.
Additionally, Dr. Culver’s lab is extending diffuse optical tomographic imaging of human brain function through methods development for detecting and efficiently sensoring motion artefact and in depth analyses of imaging grid designs on in-vivo data quality.
Additionally, the lab has been extending the reach of high-density DOT methods to far reaching settings, establishing HD-DOT imaging in Cali, Columbia.