Margrie, T. | bioRxiv Science

bioRxiv2021

Functional and multiscale 3D structural investigation of brain tissue through correlative in vivo physiology, synchrotron micro-tomography and volume electron microscopy

Attributing in vivo neurophysiology to the brains ultrastructure requires a large field of view containing contextual anatomy. Electron microscopy (EM) is the gold standard technique to identify ultrastructure, yet acquiring volumes containing full mammalian neural circuits is challenging and time consuming using EM. Here, we show that synchrotron X-ray computed tomography (SXRT) provides rapid imaging of EM-prepared tissue volumes of several cubic millimetres. Resolution was sufficient for distinguishing cell bodies as well as for tracing apical dendrites in olfactory bulb and hippocampus, for up to 350 m. Correlating EM with SXRT allowed us to associate dendritic spines on pyramidal cell apical dendrites in the stratum radiatum to their corresponding soma locations. Superficial pyramidal neurons had larger spine apparatus density compared to deeper ones, implying differential synaptic plasticity for superficial and deeper cells. Finally, we show that X-ray tomography and volume EM can be reliably correlated to prior in vivo imaging. Thus, combining functional measurements with multiscale X-ray microscopy and volume EM establishes a correlative workflow that enables functional and structural investigation of subcellular features in the context of cellular morphologies, tissues and ultimately whole organs.

neuroscience↗

bioRxiv2020

A cortico-collicular circuit for accurate orientation to shelter during escape

When faced with predatorial threats, escape towards shelter is an adaptive action that offers long-term protection against the attacker. From crustaceans to mammals, animals rely on knowledge of safe locations in the environment to instinctively execute rapid shelter-directed escape actions 1,2. While previous work has identified neural mechanisms of escape initiation3-5, it is not known how the escape circuit incorporates spatial information to execute rapid flights along the most efficient route to shelter. Here we show that mouse retrosplenial cortex (RSP) and superior colliculus (SC) form a circuit that encodes shelter direction vector and is specifically required for accurately orienting to shelter during escape. Shelter direction is encoded in RSP and SC neurons in egocentric coordinates and SC shelter-direction tuning depends on RSP activity. Inactivation of the RSP-SC pathway disrupts orientation to shelter and causes escapes away from the optimal shelter-directed route, but does not lead to generic deficits in orientation or spatial navigation. We find that the RSP and SC are monosynaptically connected and form a feedforward lateral inhibition microcircuit that strongly drives the inhibitory collicular network due to higher RSP input convergence and synaptic integration efficiency in inhibitory SC neurons. This results in broad shelter direction tuning in inhibitory SC neurons and sharply tuned excitatory SC neurons. These findings are recapitulated by a biologically-constrained spiking network model where RSP input to the local SC recurrent ring architecture generates a circular shelter-direction map. We propose that this RSP-SC circuit might be specialized for generating collicular representations of memorized spatial goals that are readily accessible to the motor system during escape, or more broadly, during navigation when the goal must be reached as fast as possible.

neuroscience↗