High-density multi-fiber photometry for studying large-scale brain circuit dynamics

Abstract

Animal behavior originates from neuronal activity distributed across brain-wide networks. However, techniques available to assess large-scale neural dynamics in behaving animals remain limited. Here we present compact, chronically implantable, high-density arrays of optical fibers that enable multifiber photometry and optogenetic perturbations across many regions in the mammalian brain. In mice engaged in a texture discrimination task, we achieved simultaneous photometric calcium recordings from networks of 12-48 brain regions, including striatal, thalamic, hippocampal and cortical areas. Furthermore, we optically perturbed subsets of regions in VGAT-ChR2 mice by targeting specific fiber channels with a spatial light modulator. Perturbation of ventral thalamic nuclei caused distributed network modulation and behavioral deficits. Finally, we demonstrate multi-fiber photometry in freely moving animals, including simultaneous recordings from two mice during social interaction. High-density multi-fiber arrays are versatile tools for the investigation of large-scale brain dynamics during behavior.

Simultaneous Electrophysiology and Fiber Photometry in Freely Behaving Mice

“…Here, we combine an electrophysiological approach with GECI-based fiber photometry to simultaneously monitor both field potentials and calcium transients in freely behaving mice. Fiber photometry is an imaging method used to monitor fluorescent signals via an implanted fiber optic cannula (Adelsberger et al, 2005;Lutcke et al, 2010;Kim et al, 2016;Sych et al, 2019). Although it is still invasive, the diameter of the cannula is thinner than an endoscope.…”

Robotic Multi-Probe-Single-Actuator Inchworm Neural Microdrive

“…Apart from neural electrophysiology probes, the MPSA microdrive could also be used for other biological as well as non-biological probe translation tasks 67,68 . For example, the micro-grippers could be sized to accommodate hypodermic needles, optical fibers and ultrasonic transducers and sensors of a variety of scales.…”

Heterogeneity in striatal dopamine circuits: Form and function in dynamic reward seeking

“…One limitation to progress on this front has been the technological bottleneck preventing widespread activity measurements across large areas of deep brain tissue, like the striatum. Recent advances in large‐scale recording methods that can access subcortical structures such as high density fiber photometry and electrophysiology (Hamid et al, ; Jun et al, ; Pisano et al, ; Sych, Chernysheva, Sumanovski, & Helmchen, ) offer promise for uncovering novel functional dynamics in the striatum. These approaches, combined with brain‐wide circuit‐ and network‐level functional imaging (Decot et al, ; Heilbronner et al, ; Lohani, Poplawsky, Kim, & Moghaddam, ) will also be important for translation of rodent findings to humans. Functions of neurotransmitter co‐release from dopamine neurons: Many dopamine neurons co‐release other neurotransmitters, including GABA and glutamate (Morales & Margolis, ; Morales & Root, ; Tecuapetla et al, ; Tritsch, Ding, & Sabatini, ) and co‐release varies depending on dopamine neuron subpopulation.…”