Optogenetic stimulation of complex spatio-temporal activity patterns by acousto-optic light steering probes cerebellar granular layer integrative properties

Abstract

Optogenetics provides tools to control afferent activity in brain microcircuits. However, this requires optical methods that can evoke asynchronous and coordinated activity within neuronal ensembles in a spatio-temporally precise way. Here we describe a light patterning method, which combines MHz acousto-optic beam steering and adjustable low numerical aperture Gaussian beams, to achieve fast 2D targeting in scattering tissue. Using mossy fiber afferents to the cerebellar cortex as a testbed, we demonstrate single fiber optogenetic stimulation with micron-scale lateral resolution, >100 µm depth-penetration and 0.1 ms spiking precision. Protracted spatio-temporal patterns of light delivered by our illumination system evoked sustained asynchronous mossy fiber activity with excellent repeatability. Combining optical and electrical stimulations, we show that the cerebellar granular layer performs nonlinear integration, whereby sustained mossy fiber activity provides a permissive context for the transmission of salient inputs, enriching combinatorial views on mossy fiber pattern separation.

Implantable acousto-optic window for monitoring ultrasound-mediated neuromodulation in vivo

“… 31 Our dose-response results were similar to those of a previous ultrasound neuromodulation study 12 and other neuromodulation tools. 32 , 33 A previous study that stimulated inhibitory pathways using high-frequency longer stimulations 29 identified a poststimulant delay. Although further mechanistic studies are needed to determine the delay time in inhibitory responses with longer ultrasound stimulations, some reports might explain the delayed responses.…”

Holographic optogenetic stimulation with calcium imaging as an all optical tool for cardiac electrophysiology

“…Other available driver versions of FSLM allow for online control of the displayed holograms at lower refresh rates around several hundred frames per second and would require a more complicated software interfaced with OpenGL by Psychtoolbox or comparable software. In comparison, acousto‐optical deflectors can be operated at MHz switching rates [16] but cannot truly simultaneously stimulate several cells. Liquid crystal SLMs have slower switching rates but projection of multiple holographic spots generated by this SLM can also be time‐gated with DMDs for faster rate of selective switching of light patterns [39].…”

“…For example, stimulation of multiple cells in a network may either be performed by scanning the focused laser [12,13] or splitting the incident beam to multiple spots [14] to flexibly target any cells in a field of view while simultaneously observing the neuronal or cardiac network activity using fluorescence imaging. Galvanometer mirrors [12,15] or acousto‐optical deflectors [16] which can be operated in kHz or MHz rate, respectively, can also be used to scan the laser spot in multiple positions within the cell or on multiples of cells. However, the photostimulation occurs sequentially and the temporal resolution will be limited by the dwell time necessary to optogenetically stimulate the individual cells [17].…”

Acousto-optic deflectors in experimental neuroscience: overview of theory and applications

“…Quast et al analyzed the development of inhibitory sensory maps and how they change over time, showing that inhibitory sensory maps become broader during development [110]. Hernandez et al discussed the use of optogenetics to induce complex patterns of activity in the cerebellar granular layer, showing that this technique can reveal insights into the integrative properties of this brain region [111].…”