Calcium imaging and 3D photostimulation are critical tools for understanding brain function, which is an enormous scientific challenge that is being addressed through multiple large-scale national and international efforts, including the BRAIN Initiative, the Brain Activity Map (BAM) and the Human Brain Project.
Microscopes built with spatial light modulators enable researchers to use calcium imaging and photostimulation three-dimensionally and with random access control, both in vitro and in vivo, to map neural circuits. Using digital holography, spatial light modulators (SLMs) offer efficient use of light by redirecting all of the available light to only the desired focal points within a three dimensional volume as opposed to simply spatially blocking illumination within a two dimensional plane. Similarly, the generalized phase contrast technique can use SLMs to efficiently illuminate complex and dynamic extended two-dimensional shapes deep in tissue. These techniques have been used to study a wide range of samples, from single dendritic spines to larger three dimensional populations of neurons, and has allowed scientists to study complex neural activity such as the integration of inputs arriving on multiple dendritic branches, which is by its nature a three dimensional problem.
|Actual image of neuron sample while it is continuously illuminated by SLM with corresponding time lapse traces of Ca signals.|
Boulder Nonlinear Systems (BNS) is currently working to push the boundaries of these techniques even further through the development of new SLM backplanes, high-speed addressing schemes, and low latency 16-bit PCIe drivers to achieve 1 ms closed-loop modulation speeds and beyond, thus providing the temporal resolution to capture the fastest neural signaling dynamics. In addition, BNS is developing large format backplanes with higher pixel counts to expand the addressable field of view of these techniques and bridge the gap between cellular-level imaging and network-level mapping.