Bayesian In Vivo Tracking of Synapses using Joint Poisson Deconvolution and Diffeomorphic Registration

2026-05-13

AI Summary

This work addresses the challenges of accurate detection and tracking of densely packed synapses in in vivo two-photon imaging, which are hindered by low signal-to-noise ratio, nonlinear tissue deformations, fluorescence intensity fluctuations, and blur induced by the microscope’s point spread function. The authors propose a template-based Bayesian framework that, for the first time, unifies a Poisson observation model, a Gaussian point spread function, and diffeomorphic registration within a single posterior inference procedure. This joint approach simultaneously performs image denoising, deconvolution, motion correction, and synaptic brightness estimation, while also yielding confidence intervals for the inferred parameters. Validated on both 2D+t simulated data and real 3D+t in vivo imaging of mouse cortex over two weeks, the method significantly improves the precision of synapse localization and the robustness of longitudinal tracking in high-density environments.

Abstract

Synapses are densely packed submicron structures that dynamically reorganize during learning and memory formation. Longitudinal \textit{in vivo} imaging of fluorescently tagged synaptic receptors offers a promising opportunity to study large-scale synaptic dynamics and how these processes are disrupted in neurological disease. However, in vivo imaging with 2-photon microscopy uses low laser power and therefore suffers from low signal-to-noise ratio (SNR) and high shot noise, nonlinear tissue motion between days, nonstationary fluctuations in synaptic fluorescence, and significant blur induced by the microscope point spread function (PSF). Together, these factors make it challenging to detect and track synapses, especially in regions with high synaptic density. This paper presents a novel template-based framework for modeling synapses as varying luminance point sources that move under a nonlinear tissue deformation. Taking a unified Bayesian approach, we apply this model to microscopy data by deriving a posterior that incorporates a diffeomorphic mapping for domain warping, a Gaussian point spread function for the imaging process, and a Poisson observation model for raw photon counts. The Bayesian solution simultaneously: (1) Constructs a probabilistic template of synapse locations, (2) denoises and deconvolves the image data, (3) infers fluorescence intensities, (4) performs diffeomorphic image registration to correct for tissue motion, and (5) provides confidence regions for these parameter estimates. We demonstrate the framework on both a 2D+t simulated dataset and a 3D+t longitudinal \textit{in vivo} microscopy dataset of fluorescent synapses imaged in a mouse over two weeks.

Problem

• synapse tracking
• in vivo imaging
• low SNR
• tissue motion
• microscopy deconvolution

Innovation

• Bayesian inference
• Poisson deconvolution
• Diffeomorphic registration
• In vivo synapse tracking
• Point spread function