Abstract

The pattern of neural activity evoked by a stimulus can be substantially affected by ongoing spontaneous activity. Separating these two types of activity is particularly important for calcium imaging data given the slow temporal dynamics of calcium indicators. Here we present a statistical model that decouples stimulus-driven activity from low dimensional spontaneous activity in this case. The model identifies hidden factors giving rise to spontaneous activity while jointly estimating stimulus tuning properties that account for the confounding effects that these factors introduce. By applying our model to data from zebrafish optic tectum and mouse visual cortex, we obtain quantitative measurements of the extent that neurons in each case are driven by evoked activity, spontaneous activity, and their interaction. By not averaging away potentially important information encoded in spontaneous activity, this broadly applicable model brings new insight into population-level neural activity within single trials.

Highlights

  • MethodsZebrafish recordingsAll procedures were performed with approval from The University of Queensland Animal Ethics Committee (approval certificate number QBI/152/16/ARC)

  • The nervous system constructs internal representations of its sensory environment by coordinating patterns of neural activity

  • An important question in neuroscience is how the joint activity of populations of neurons encode sensory information. This can be challenging to answer because neural populations activate spontaneously, biasing stimulus-response estimates

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Summary

Methods

Zebrafish recordingsAll procedures were performed with approval from The University of Queensland Animal Ethics Committee (approval certificate number QBI/152/16/ARC). Nacre zebrafish (Danio rerio) embryos expressing elavl3:H2B-GCaMP6s, of either sex, were collected and raised according to established procedures [40] and kept under a 14/10 hr on/off light cycle. Calcium imaging was performed at a depth of 70 μm from the dorsal surface of the tectal midline. Time-lapse two-photon images were acquired using a Zeiss LSM 710 inverted two-photon microscope. A custom-made inverter tube composed of a pair of beam-steering mirrors and two identical 60 mm focal length lenses arranged in a 4f configuration was used to allow imaging with a 40X/1.0 NA water-dipping objective (Zeiss) in an upright configuration. Samples were excited via a Spectra-Physics Mai TaiDeepSee Ti:Sapphire laser (Spectra-Physics) at an excitation wavelength of 940 nm and the emitted light was bandpass filtered (500–550 nm). To improve the stability of the recording, chambers were allowed to settle for three hours prior to start of two-photon imaging

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