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

Abstract

Animal behavior originates from neuronal activity distributed and coordinated across brain-wide networks. However, techniques to assess large-scale brain circuit dynamics in behaving animals remain limited. Here we present compact, high-density arrays of optical fibers that can be chronically implanted into the mammalian brain, enabling multi-fiber photometry as well as optogenetic perturbations across many regions. In mice engaged in a texture discrimination task we achieved simultaneous photometric calcium recordings from networks of 12 to 48 brain regions, including striatal, thalamic, hippocampal, and cortical areas. Furthermore, we optically perturbed specific subsets of regions in VGAT-ChR2 mice by using a spatial light modulator to address the respective fiber channels. 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. Thus, high-density multi-fiber arrays are simple, low-cost, and versatile tools that open novel ways to investigate large-scale brain dynamics during behavior.

Resolving the Micro-Macro Disconnect to Address Core Features of Seizure Networks

“…For example, expression can be limited to neurons that rely on promoter sequences specific to glutamatergic neurons (e.g., VGLUT1, a synaptic glutamate transporter) to determine local excitatory neuron activation during seizures. Calcium signal from these neurons can be assessed at the local population level (average activity) with a chronically implanted fiber optic probe (fiber photometry) at a single site (Gunaydin et al, 2014; Figure 4B) or up to 48 locations throughout the brain (Kim et al, 2016a;Sych et al, 2018; Figure 4E). Similarly, the average calcium activity can be visualized across the entire cortical surface with a wide-field macroscope to visualize seizure spread through the excitatory network (Rossi et al, 2017;Liou et al, 2018; Figure 4D).…”

Mesoscale brain dynamics reorganizes and stabilizes during learning

“…To measure large-scale brain activity during learning, we applied multi-fiber photometry (25) (Fig. 1D; 20 Hz frame rate).…”

“…In 4 mice we implanted 48-fiber arrays (25), which allowed us to investigate learning-related network dynamics on an even broader scale, targeting additionally multiple brain regions in frontal and posterior cortex as well as in the amygdala ( Fig. 6A; Table S1).…”

“…However, this approach has been applied to either individual (10,22,11) or few regions (23) or, in the case of wide-field calcium imaging (24), has been limited to the cortical surface. To enable more comprehensive chronic brain activity measurements, we recently introduced high-density multi-fiber photometry (25), which can simultaneously target many cortical and subcortical regions of the mouse brain. Here we use this approach to track large-scale brain activity during learning and reveal salient learningassociated changes.…”

Simultaneous electrophysiological recording 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.…”