Optical Manipulation and Recording of Neural Activity with Wavefront Engineering

Abstract

One of the central goals of neuroscience is to decipher the specific contributions of neural mechanisms to different aspects of sensory perception. Since achieving this goal requires tools capable of precisely perturbing and monitoring neural activity across a multitude of spatiotemporal scales, this aim has inspired the innovation of many optical technologies capable of manipulating and recording neural activity in a minimally invasive manner. The interdisciplinary nature of neurophotonics requires a broad knowledge base in order to successfully develop and apply these technologies, and one of the principal aims of this chapter is to provide some basic but fundamental background information in terms of both physiology and optics in the context of all-optical two-photon neurophysiology experiments. Most of this information is expected to be familiar to readers experienced in either domain, but is presented here with the aim of bridging the divide between disciplines in order to enable physicists and engineers to develop useful optical technologies or for neuroscientists to select appropriate tools and apply them to their maximum potential.The first section of this chapter is dedicated to a brief overview of some basic principles of neural physiology relevant for controlling and recording neuronal activity using light. Then, the selection of appropriate actuators and sensors for manipulating and monitoring particular neural signals is discussed, with particular attention paid to kinetics and sensitivity. Some considerations for minimizing crosstalk in optical neurophysiology experiments are also introduced. Next, an overview of the state-of-the-art optical technologies is provided, including a description of suitable laser sources for two-photon excitation according to particular experimental requirements. Finally, some detailed, technical, information regarding the specific wavefront engineering approaches known as Generalized Phase Contrast (GPC) and temporal focusing is provided.

Scanless two-photon voltage imaging

“…The diffraction grating was oriented perpendicular to the optical axis and the illumination angle was chosen such that the first diffraction order of the central wavelength propagated along the optical axis. This orientation did not coincide with the blaze angle, and hence was not the most efficient 35 but allowed the temporal focusing plane of each of the holographic discs to coincide with the focal plane of the objective lens. A pair of telescopes comprised of L11, L12, L7 and the objective lens was used to de-magnify and relay the holographic spots on to the sample plane.…”

“…In principle, the optical sectioning and longer excitation wavelengths inherent to multi-photon excitation ought to be capable of recording neural activity with cellular resolution from deeper cortical layers 34 ; indeed, 2P laser scanning microscopy (2P-LSM) is by far the most prevalent approach for calcium imaging of neural activity with single cell resolution in scattering tissue 35 . However, the acquisition rate of conventional 2P-LSM is limited and millisecond transients such as APs can only be detected by drastically reducing the field of view (FOV) [36][37][38][39] .…”