Vissers, N. | Search bioRxiv

bioRxiv2026

High-throughput serial two-photon tomography with BakingTray and BrainSaw

Volumetric imaging is increasingly important in fields such as neuroscience, where quantifying structure and mapping features are inherently three-dimensional problems. Block-face serial two-photon tomography (STPT) has emerged as a powerful approach for high-resolution, whole-organ volumetric imaging. STPT avoids complex sample preparation and balances image quality, speed, and scalability. However, STPT remains niche, in part because of the absence of flexible, general-purpose control software. Here we present BakingTray, an open-source software platform for STPT that extends ScanImage. BakingTrays modular framework accommodates diverse hardware configurations and allows users to build systems customised to their needs. Twelve such systems, which we call BrainSaws, have been constructed worldwide since 2016, with more under construction, and have so far contributed to 35 research papers. The three systems at the Sainsbury Wellcome Centre alone have acquired over 7,000 samples in a busy multi-user facility. We demonstrate the platform across its core neuroscience applications: electrode track localisation, brain-wide cell counting, and bulk projection mapping. Beyond these, we map the cell-type-specific synaptic output of inhibitory neurons in the ventral lateral geniculate nucleus and, with whole-mount staining, amyloid plaques brain-wide in a mouse model of Alzheimers disease. BakingTray is a mature platform for groups or facilities needing a customised volumetric imaging solution, whether built new or converted cheaply from an existing two-photon microscope.

neuroscience↗

bioRxiv2024

Overwriting an instinct: visual cortex instructs learning to suppress fear responses

Fast instinctive responses to environmental stimuli can be crucial for survival, but are not always optimal. Based on prior experience, animals can thus adapt their behavior and suppress instinctive reactions. However, the neural pathways mediating such ethologically relevant forms of learning remain unclear. We show that posterolateral higher visual areas (plHVAs) are crucial for learning to suppress escapes from innate visual threats through a top-down pathway involving the ventrolateral geniculate nucleus (vLGN). plHVAs are no longer necessary after learning: instead, the learnt behavior relies on plasticity within vLGN populations that exert inhibitory control over fear responses. vLGN neurons receiving input from plHVAs enhance their responses to visual threat stimuli during learning through endocannabinoid-mediated long-term suppression of their inhibitory inputs. We thus reveal the detailed circuit, cellular and synaptic mechanisms underlying experience-dependent suppression of fear responses through a novel corticofugal pathway.

neuroscience↗