Parallel Optical Control of Spatiotemporal Neuronal Spike Activity Using High-Speed Digital Light Processing

Abstract

Neurons in the mammalian neocortex receive inputs from and communicate back to thousands of other neurons, creating complex spatiotemporal activity patterns. The experimental investigation of these parallel dynamic interactions has been limited due to the technical challenges of monitoring or manipulating neuronal activity at that level of complexity. Here we describe a new massively parallel photostimulation system that can be used to control action potential firing in in vitro brain slices with high spatial and temporal resolution while performing extracellular or intracellular electrophysiological measurements. The system uses digital light processing technology to generate 2-dimensional (2D) stimulus patterns with >780,000 independently controlled photostimulation sites that operate at high spatial (5.4 μm) and temporal (>13 kHz) resolution. Light is projected through the quartz–glass bottom of the perfusion chamber providing access to a large area (2.76 mm × 2.07 mm) of the slice preparation. This system has the unique capability to induce temporally precise action potential firing in large groups of neurons distributed over a wide area covering several cortical columns. Parallel photostimulation opens up new opportunities for the in vitro experimental investigation of spatiotemporal neuronal interactions at a broad range of anatomical scales.

Digital micromirror based near-infrared illumination system for plasmonic photothermal neuromodulation

“…Several optical configurations have been implemented as light pattern generator to avoid illumination vignette. Expanded collimation [22], diffuser [23] and beam shaper [24] have been used for light homogenization, but severe power loss limits maximum applicable power density. Fly eye lens makes flat illumination by dividing each spatial beam path, but the lens dimension should be customized to guide light pattern into a microscope.…”

Cellular neuroanatomy of rat presubiculum

“…8A). Thus, only strong, synchronous and sustained synaptic inputs from afferents corresponding to a given head direction seem likely to assure maintained firing (Jerome et al, 2011). The tetrodotoxininsensitive, dendritic sodium current of presubicular principal cells (Fricker et al, 2009) might function in a similar way to dendritic calcium signals in direction-sensitive visual cortex cells (Jia et al, 2010), boosting correlated inputs to induce firing in response to directional inputs (Gasparini et al, 2004;Losonczy et al, 2008).…”

Two-photon optogenetic toolbox for fast inhibition, excitation and bistable modulation

“…Most such studies have involved synchronous control of genetically targeted cell populations over millimeter-scale spatial domains 3–19 , for example, in studies of sleep-wake transitions 5 , parkinsonian circuitry 6,7 , gamma rhythms 8–10 , feeding behavior 11,12 , olfaction 13 , anxiety and fear 14–17 and memory storage 18,19 . Yet methods for guiding spatial delivery of light excitation itself could allow improved precision and complexity in optogenetic modulation 20–26 , and indeed single-photon guided-light strategies have been used in mammalian tissue 27,28 for optogenetic circuit mapping 29,30 and dissection of anxiety circuitry 14 . Even more spatially precise control has been achieved using TPLSM 31 methods for generating restricted excitation volumes, and such methods have advanced the study of circuit wiring, activity and plasticity (reviewed in ref.…”