Daste, S. | bioRxiv Science

bioRxiv2024

Aberration correction in long GRIN lens-based microendoscopes for extended field-of-view two-photon imaging in deep brain regions

Two-photon (2P) fluorescence imaging through gradient index (GRIN) lens-based endoscopes is fundamental to investigate the functional properties of neural populations in deep brain circuits. However, GRIN lenses have intrinsic optical aberrations, which severely degrade their imaging performance. GRIN aberrations decrease the signal-to-noise ratio (SNR) and spatial resolution of fluorescence signals, especially in lateral portions of the field-of-view (FOV), leading to restricted FOV and smaller number of recorded neurons. This is especially relevant for GRIN lenses of several millimeters in length, which are needed to reach the deeper regions of the rodent brain. We have previously demonstrated a novel method to enlarge the FOV and improve the spatial resolution of 2P microendoscopes based on GRIN lenses of length < 4.1 mm (Antonini et al. eLife 2020). However, previously developed microendoscopes were too short to reach the most ventral regions of the mouse brain. In this study, we combined optical simulations with fabrication of aspherical polymer microlenses through three-dimensional (3D) microprinting to correct for optical aberrations in long (length > 6 mm) GRIN lens-based microendoscopes (diameter, 500 {micro}m). Long corrected microendoscopes had improved spatial resolution, enabling imaging in significantly enlarged FOVs. Moreover, using synthetic calcium data we showed that aberration correction enabled detection of cells with higher SNR of fluorescent signals and decreased cross-contamination between neurons. Finally, we applied long corrected microendoscopes to perform large-scale and high precision recordings of calcium signals in populations of neurons in the olfactory cortex, a brain region laying approximately 5 mm from the brain surface, of awake head-tethered mice. Long corrected microendoscopes are powerful new tools enabling population imaging with unprecedented large FOV and high spatial resolution in the most ventral regions of the mouse brain.

neuroscience↗

bioRxiv2023

Stochastic coding: a conserved feature of odor representations and its implications for odor discrimination

Sparse coding is thought to improve discrimination of sensory stimuli by reducing overlap between their representations. Two factors, however, can offset sparse codings advantages. Similar sensory stimuli have significant overlap, and responses vary across trials. To elucidate the effect of these two factors, we analyzed odor responses in the fly and mouse olfactory regions implicated in learning and discrimination -- the Mushroom Body (MB) and the Piriform Cortex (PCx). In both species, we show that neuronal responses fall along a continuum from extremely reliable across trials to extremely variable or stochastic. Computationally, we show that the range of observed variability arises from probabilistic synapses in inhibitory feedback connections within central circuits rather than sensory noise, as is traditionally assumed. We propose this coding scheme to be advantageous for coarse- and fine-odor discrimination. More reliable cells enable quick discrimination between dissimilar odors. For similar odors, however, these cells overlap, and do not provide distinguishing information. By contrast, more unreliable cells are decorrelated for similar odors, providing distinguishing information, though this requires extended training with more trials. Overall, we have uncovered a stochastic coding scheme that is conserved in vertebrates and invertebrates, and we identify a candidate mechanism, based on variability in a winner-take-all inhibitory circuit, that improves discrimination with training.

neuroscience↗