Biology subjects

Fan, L. Z.

Publications and source records attributed to Fan, L. Z..

4 recordsLinked to original sources

bioRxiv2025

CLOOSE: An open-source platform for optical closed-loop experiments

Brain-Computer Interfaces (BCI) have catalyzed advancements in both clinical applications and basic neuroscience research. However, technical barriers such as steep learning curves and complex synchronization requirements often impede their widespread adoption. In response to the increasing demand for optical BCI experiments and to the technical challenges associated with their implementation, we introduce CLOOSE (Closed-loop Optical Open-Source Experiments), a versatile platform designed to standardize, simplify, and accelerate closed-loop experiments with functional imaging data. CLOOSE interfaces easily with any frame-based imaging system via TCP/IP, allowing for real-time data streaming and distributed computation. Benchmark tests validate CLOOSEs real-time accuracy in image registration, signal processing, and analysis at imaging frequencies [≥]1 kHz, making it the first optical BCI compatible with voltage indicators. Throughout the paper we showcase CLOOSEs versatility in supporting several neurofeedback paradigms: from single neuron to population dynamics, multiplane imaging, and online (and offline) z-tracking. CLOOSEs functionality is easily accessible to users with minimal coding experience through an intuitive graphical interface for experiment setup and real-time performance monitoring. By significantly lowering the barrier to performing technically demanding closed-loop experiments, CLOOSE advances the streamlining, standardization, and democratization of online image analysis and neurofeedback BCI paradigms, opening new avenues for precise manipulation and real-time readout of neuronal activity in health and disease.

neuroscience↗

bioRxiv2023

Optical segmentation-based compressed readout of neuronal voltage dynamics

Functional imaging of biological dynamics generally begins with acquiring time-series images, followed by quantifying spatially averaged intensity traces for the regions of interest (ROIs). The conventional pipeline discards a substantial portion of the acquired data when quantifying intensity traces, indicative of inefficient data acquisition. Here we propose a conceptually novel acquisition pipeline that assigns each ROI to a single pixel in the detector, enabling optimally compressed acquisition of the intensity traces. As a proof-of-principle, we implemented a detection module composed of a pair of spatial light modulators and a microlens array, which segments the original image into multiple subimages by introducing distinct angular shifts to each ROI. Each subimage exclusively encodes the signal for the corresponding ROI, facilitating the compressed readout of its intensity trace using a single pixel. This spatial compression allowed for maximizing the temporal information without compromising the spatial information on ROIs. Harnessing our novel approach, we demonstrate the recording of circuit-scale neuronal voltage dynamics at over 5 kHz sampling rate, revealing the individual action potential waveforms within subcellular structures, as well as their submillisecond-scale temporal delays.

neuroscience↗

bioRxiv2021

All-optical electrophysiology with improved genetically encoded voltage indicators reveals interneuron network dynamics in vivo

All-optical electrophysiology can be a powerful tool for studying neural dynamics in vivo, as it offers the ability to image and perturb membrane voltage in multiple cells simultaneously. The "Optopatch" constructs combine a red-shifted archaerhodopsin (Arch)-derived genetically encoded voltage indicator (GEVI) with a blue-shifted channelrhodopsin actuator (ChR). We used a video-based pooled screen to evolve Arch-derived GEVIs with improved signal-to-noise ratio (QuasAr6a) and kinetics (QuasAr6b). By combining optogenetic stimulation of individual cells with high-precision voltage imaging in neighboring cells, we mapped inhibitory and gap junction-mediated connections, in vivo. Optogenetic activation of a single NDNF-expressing neuron in visual cortex Layer 1 significantly suppressed the spike rate in some neighboring NDNF interneurons. Hippocampal PV cells showed near-synchronous spikes across multiple cells at a frequency significantly above what one would expect from independent spiking, suggesting that collective inhibitory spikes may play an important signaling role in vivo. By stimulating individual cells and recording from neighbors, we quantified gap junction coupling strengths. Together, these results demonstrate powerful new tools for all-optical microcircuit dissection in live mice.

neuroscience↗

bioRxiv2019

All-optical electrophysiology reveals excitation, inhibition, and neuromodulation in cortical layer 1

The stability of neural dynamics arises through a tight coupling of excitatory (E) and inhibitory (I) signals. Genetically encoded voltage indicators (GEVIs) can report both spikes and subthreshold dynamics in vivo, but voltage only reveals the combined effects of E and I synaptic inputs, not their separate contributions individually. Here we combine optical recording of membrane voltage with simultaneous optogenetic manipulation to probe E and I individually in barrel cortex Layer 1 (L1) neurons in awake mice. Our studies reveal how the L1 microcircuit integrates thalamocortical excitation, lateral inhibition and top-down neuromodulatory inputs. We develop a simple computational model of the L1 microcircuit which captures the main features of our data. Together, these results suggest a model for computation in L1 interneurons consistent with their hypothesized role in attentional gating of the underlying cortex. Our results demonstrate that all-optical electrophysiology can reveal basic principles of neural circuit function in vivo.\n\nOne Sentence SummaryAll-optical electrophysiology revealed the function in awake mice of an inhibitory microcircuit in barrel cortex Layer 1.

neuroscience↗