Optical developments for optogenetics

Abstract

Brain intricacies and the difficulty that scientists encounter in revealing its function with standard approaches such as electrical stimulation of neurons have led to the exploration of new tools that enable the study of neural circuits in a remote and non-invasive way. To this end, optogenetics has initialised a revolution for neuroscience in the last decade by enabling simultaneous monitoring and stimulation of specific neuronal populations in intact brain preparations through genetically targeted expression of light sensitive proteins and molecular photoswitches. In addition to ongoing molecular probe development and optimisation, novel optical techniques hold immense potential to amplify and diversify the utility of optogenetic methods. Importantly, by improving the spatio-temporal resolution of light stimulation, neural circuits can be photoactivated in patterns mimicking endogenous physiological processes. The following synopsis addresses the possibilities and limitations of optical stimulation methods applied to and developed for activation of neuronal optogenetic tools.

GPC light shaping a supercontinuum source

“…For example, in two-photon optogenetics research [5], one would like to selectively illuminate intricate patterns of dendrites or axons within neurons [6]. As laser sources typically have limited shapes, many light shaping approaches have been studied to address different demands such as efficiency, speed, beam quality or economy concerns.…”

Comparison of nematic liquid-crystal and DMD based spatial light modulation in complex photonics

“…Spatial light modulators (SLMs), allowing for precise and dynamic shaping of light beams via computer interface, have opened up numerous new possibilities for photonics in complex environments [1][2][3][4][5][6][7][8][9][10][11]. Amongst other important directions, intense research efforts worldwide exploit SLM-based beam-shaping technologies for improving methods of optical imaging deep inside living tissues.…”

GPC light shaper for speckle-free one- and two-photon contiguous pattern excitation

“…A variety of shapes bounded by steep edges are desirable in laser cutting or engraving. In two-photon optogenetics research [3], one would like to selectively illuminate intricate patterns of dendrites or axons within neurons, preferably with minimal noise or speckles.…”

“…Extended intensity patterns formed by aggregating spots with differing phase values and overlapping point spread functions thus results in speckles that resemble noise [20]. The intensity fluctuations in speckled extended intensity patterns become a problem when they are enhanced by twophoton excitation such as in direct laser writing [21] or in two-photon optogenetics [3].…”

“…Unlike speckled or discontinuous patterns, light distributions with contiguous intensity and phase remain localized while propagating enabling extended optical manipulation [1,22,24]. Instead of a focusing geometry, GPC uses an imaging geometry, hence avoiding dispersion effects which makes it advantageous for use with multiple wavelengths [25] or temporal focusing [2,3].…”