Psychophysical properties of odor processing can be quantitatively described by relative action potential latency patterns in mitral and tufted cells

Electrophysiological and population imaging data in rodents show that olfactory bulb (OB) activity is profoundly modulated by the odor sampling process while behavioral experiments indicate that odor discrimination can occur within a single sniff. This paper addresses the question of whether action potential (AP) latencies occurring across the mitral and tufted cell (M/TC) population within an individual sampling cycle could account for the psychophysical properties of odor processing. To determine this we created an OB model (50,000 M/TCs) exhibiting hallmarks of published in vivo properties and used a template-matching algorithm to assess stimulus separation. Such an AP latency-based scheme showed high reproducibility and sensitivity such that odor stimuli could be reliably separated independent of concentration. As in behavioral experiments we found that very dissimilar odors (“A vs. B”) were accurately and rapidly discerned while very similar odors (binary mixtures, 0.4A/0.6B vs. 0.6A/0.4B) required up to 90 ms longer. As in lesion studies we find that AP latency-based representation is rather insensitive to disruption of large regions of the OB. The AP latency-based scheme described here, therefore, captures both temporal and psychophysical properties of olfactory processing and suggests that the onset patterns of M/TC activity in the OB represent stimulus specific features of olfactory stimuli

BrainGlobe Atlas API: a common interface for neuroanatomical atlases

Summary: Neuroscientists routinely perform experiments aimed at recording or manipulating neural activity, uncovering physiological processes underlying brain function or elucidating aspects of brain anatomy. Understanding how the brain generates behaviour ultimately depends on merging the results of these experiments into a unified picture of brain anatomy and function. Brain atlases are crucial in this endeavour: by outlining the organization of brain regions they provide a reference upon which our understanding of brain function can be anchored. More recently, digital high-resolution 3d atlases have been produced for several model organisms providing an invaluable resource for the research community. Effective use of these atlases depends on the availability of an application programming interface (API) that enables researchers to develop software to access and query atlas data. However, while some atlases come with an API, these are generally specific for individual atlases, and this hinders the development and adoption of open-source neuroanatomy software. The BrainGlobe atlas API (BG-Atlas API) overcomes this problem by providing a common interface for programmers to download and process data across a variety of model organisms. By adopting the BG-Atlas API, software can then be developed agnostic to the atlas, increasing adoption and interoperability of packages in neuroscience and enabling direct integration of different experimental modalities and even comparisons across model organisms

Mapping brain circuitry with a light microscope

The beginning of the 21st century has seen a renaissance in light microscopy and anatomical tract tracing that together are rapidly advancing our understanding of the form and function of neuronal circuits. The introduction of instruments for automated imaging of whole mouse brains, new cell type–specific and trans-synaptic tracers, and computational methods for handling the whole-brain data sets has opened the door to neuroanatomical studies at an unprecedented scale. We present an overview of the present state and future opportunities in charting long-range and local connectivity in the entire mouse brain and in linking brain circuits to function

Visualizing anatomically registered data with Brainrender

Three-dimensional (3D) digital brain atlases and high-throughput brain wide imaging techniques generate large multidimensional datasets that can be registered to a common reference frame. Generating insights from such datasets depends critically on visualization and interactive data exploration, but this a challenging task. Currently available software is dedicated to single atlases, model species or data types, and generating 3D renderings that merge anatomically registered data from diverse sources requires extensive development and programming skills. Here, we present brainrender: an open-source Python package for interactive visualization of multidimensional datasets registered to brain atlases. Brainrender facilitates the creation of complex renderings with different data types in the same visualization and enables seamless use of different atlas sources. High-quality visualizations can be used interactively and exported as high-resolution figures and animated videos. By facilitating the visualization of anatomically registered data, brainrender should accelerate the analysis, interpretation, and dissemination of brain-wide multidimensional data

Multisensory coding of angular head velocity in the retrosplenial cortex

To successfully navigate the environment, animals depend on their ability to continuously track their heading direction and speed. Neurons that encode angular head velocity (AHV) are fundamental to this process, yet the contribution of various motion signals to AHV coding in the cortex remains elusive. By performing chronic single-unit recordings in the retrosplenial cortex (RSP) of the mouse and tracking the activity of individual AHV cells between freely moving and head-restrained conditions, we find that vestibular inputs dominate AHV signaling. Moreover, the addition of visual inputs onto these neurons increases the gain and signal-to-noise ratio of their tuning during active exploration. Psychophysical experiments and neural decoding further reveal that vestibular-visual integration increases the perceptual accuracy of angular self-motion and the fidelity of its representation by RSP ensembles. We conclude that while cortical AHV coding requires vestibular input, where possible, it also uses vision to optimize heading estimation during navigation

Accurate determination of marker location within whole-brain microscopy images

High-resolution whole-brain microscopy provides a means for post hoc determination of the location of implanted devices and labelled cell populations that are necessary to interpret in vivo experiments designed to understand brain function. Here we have developed two plugins (brainreg and brainreg-segment) for the Python-based image viewer napari, to accurately map any object in a common coordinate space. We analysed the position of dye-labelled electrode tracks and two-photon imaged cell populations expressing fluorescent proteins. The precise location of probes and cells were physiologically interrogated and revealed accurate segmentation with near-cellular resolution

Neuronal Oscillations Enhance Stimulus Discrimination by Ensuring Action Potential Precision

Although oscillations in membrane potential are a prominent feature of sensory, motor, and cognitive function, their precise role in signal processing remains elusive. Here we show, using a combination of in vivo, in vitro, and theoretical approaches, that both synaptically and intrinsically generated membrane potential oscillations dramatically improve action potential (AP) precision by removing the membrane potential variance associated with jitter-accumulating trains of APs. This increased AP precision occurred irrespective of cell type and—at oscillation frequencies ranging from 3 to 65 Hz—permitted accurate discernment of up to 1,000 different stimuli. At low oscillation frequencies, stimulus discrimination showed a clear phase dependence whereby inputs arriving during the trough and the early rising phase of an oscillation cycle were most robustly discriminated. Thus, by ensuring AP precision, membrane potential oscillations dramatically enhance the discriminatory capabilities of individual neurons and networks of cells and provide one attractive explanation for their abundance in neurophysiological systems

Population diversity and function of hyperpolarization-activated current in olfactory bulb mitral cells

Although neurons are known to exhibit a broad array of intrinsic properties that impact critically on the computations they perform, very few studies have quantified such biophysical diversity and its functional consequences. Using in vivo and in vitro whole-cell recordings here we show that mitral cells are extremely heterogeneous in their expression of a rebound depolarization (sag) at hyperpolarized potentials that is mediated by a ZD7288-sensitive current with properties typical of hyperpolarization-activated cyclic nucleotide gated (HCN) channels. The variability in sag expression reflects a functionally diverse population of mitral cells. For example, those cells with large amplitude sag exhibit more membrane noise, a lower rheobase and fire action potentials more regularly than cells where sag is absent. Thus, cell-to-cell variability in sag potential amplitude reflects diversity in the integrative properties of mitral cells that ensures a broad dynamic range for odor representation across these principal neurons

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

Understanding the function of biological tissues requires a coordinated study of physiology and structure, exploring volumes that contain complete functional units at a detail that resolves the relevant features. Here, we introduce an approach to address this challenge: Mouse brain tissue sections containing a region where function was recorded using in vivo 2-photon calcium imaging were stained, dehydrated, resin-embedded and imaged with synchrotron X-ray computed tomography with propagation-based phase contrast (SXRT). SXRT provided context at subcellular detail, and could be followed by targeted acquisition of multiple volumes using serial block-face electron microscopy (SBEM). In the olfactory bulb, combining SXRT and SBEM enabled disambiguation of in vivo-assigned regions of interest. In the hippocampus, we found that superficial pyramidal neurons in CA1a displayed a larger density of spine apparati than deeper ones. Altogether, this approach can enable a functional and structural investigation of subcellular features in the context of cells and tissues