Multisite cell‐ and neural‐dynamics‐resolving deep brain imaging in freely moving mice with implanted reconnectable fiber bundles

Abstract

We demonstrate a reconnectable implantable ultraslim fiber-optic microendoscope that integrates a branching fiber bundle (BFB) with gradient-index fiber lenses, enabling a simultaneous fluorescence imaging of individual cells in distinctly separate brain regions, including brain structures as distant as the neocortex and hippocampus. We show that fluorescence images of individual calcium-indicator-expressing neurons in the brain of freely moving transgenic mice can be recorded, via the implanted BFB probe, in parallel with time-and cell-resolved traces of calcium signaling, thus enabling correlated circuitdynamics studies at-multiple sites within the brain of freely moving animals.

Implantable graded‐index fibers for neural‐dynamics‐resolving brain imaging in awake mice on an air‐lifted platform

“…With the high-frequency noise and slowly varying wave components of the NCaMP7 fluorescence return suppressed via suitable filtering [22,23], the time-dependent fiberprobe readout is approximated as a sum F + ΔF(t) of a largely time-independent term F, related to the fluorescence background collected by the fiber probe and a waveform ΔF(t), providing a readout of neuronal activity.…”

“…Fiber bundles, consisting of thousands of individual optical fibers, have proven instrumental for a wide variety of brain imaging modalities, including the imaging of neuronal circuits in animal models [17][18][19], as well as multicolor fluorescence [20] and Raman [21] imaging in live brain. As a step toward adapting fiber-bundle probes to the needs of long-term deep-brain imaging, reconnectable fiber bundles have been demonstrated [22], enabling a high-quality image transmission in chronic brain studies of deep areas in awake brain, as well as multisite fiberoptic cell-and neural-dynamics-resolving brain imaging in freely moving mice [23].…”

“…Suitably designed GRIN lenses have been shown to expand the imaging depth range of head-mounted wearable microscopes to enable an imaging of deep-brain areas [10,24]. GRIN fibers, on the other hand, have been successfully integrated with both single-mode optical fibers [25,26] and imaging fiber bundles [23,27], leading to the development of fiber-optic microprobes for minimally invasive in vivo low-coherence interferometry, optical coherence tomography and depth-resolved microendoscopy [25][26][27].…”

Dense Packed Drivable Optrode Array for Precise Optical Stimulation and Neural Recording in Multiple-Brain Regions

“…The large scale of the human brain contains an estimated 85 billion neurons, 100 trillion synapses, and 100 types of chemical neurotransmitters, which results in complicated systematic neural activity . To understand the brain function and map the brain architecture, different technologies have been developed, such as magnetic resonance imaging, , optical imaging, , and electrophysiology recording. − Up to now, electrophysiology recording provides the greatest temporal resolution and frequency range, which has great potential to uncover the mysterious veil of the brain . The most widely applied tools for neural activity recording are neural implantable probes. − However, limited by the number and distribution of recording electrodes, neuroscientists are still far from achieving recording densities capable of whole-brain mapping .…”

Resolving neural states from optical neural response readout

“…Such a setting can be implemented in awake, freely behaving animals by using wearable miniscopes [27,28]-a rapidly progressing technology that continues to revolutionize the field of neuroscience. In the second scheme, a fiber-optic neurointerface [29][30][31][32][33][34][35][36][37] is used to deliver laser radiation to a targeted neuron or neural population, as well as to collect the fluorescence return signal. In both settings, neural dynamics is read out using a GECI with a typical contrast ratio ∆S/S ≈ 0.3.…”