Geometry of abstract learned knowledge in the hippocampus.

Hippocampal neurons encode physical variables1-7 such as space1 or auditory frequency6 in cognitive maps8. In addition, functional magnetic resonance imaging studies in humans have shown that the hippocampus can also encode more abstract, learned variables9-11. However, their integration into existing neural representations of physical variables12,13 is unknown. Here, using two-photon calcium imaging, we show that individual neurons in the dorsal hippocampus jointly encode accumulated evidence with spatial position in mice performing a decision-making task in virtual reality14-16. Nonlinear dimensionality reduction13 showed that population activity was well-described by approximately four to six latent variables, which suggests that neural activity is constrained to a low-dimensional manifold. Within this low-dimensional space, both physical and abstract variables were jointly mapped in an orderly manner, creating a geometric representation that we show is similar across mice. The existence of conjoined cognitive maps suggests that the hippocampus performs a general computation-the creation of task-specific low-dimensional manifolds that contain a geometric representation of learned knowledge.

A quantitative description of macaque ganglion cell responses to natural scenes: the interplay of time and space.

KEY POINTS: Responses to natural scenes are the business of the retina. We find primate ganglion cell responses to such scenes consistent with those to simpler stimuli. A biophysical model confirmed this and predicted ganglion cell responses with close to retinal reliability. Primate ganglion cell responses to natural scenes were driven by temporal variations in colour and luminance over the receptive field centre caused by eye movements, and little influenced by interaction of centre and surround with structure in the scene. We discuss implications in the context of efficient coding of the visual environment. Much information in a higher spatiotemporal frequency band is concentrated in the magnocellular pathway. ABSTRACT: Responses of visual neurons to natural scenes provide a link between classical descriptions of receptive field structure and visual perception of the natural environment. A natural scene video with a movement pattern resembling that of primate eye movements was used to evoke responses from macaque ganglion cells. Cell responses were well described through known properties of cell receptive fields. Different analyses converge to show that responses primarily derive from the temporal pattern of stimulation derived from eye movements, rather than spatial receptive field structure beyond centre size and position. This was confirmed using a model that predicted ganglion cell responses close to retinal reliability, with only a small contribution of the surround relative to the centre. We also found that the spatiotemporal spectrum of the stimulus is modified in ganglion cell responses, and this can reduce redundancy in the retinal signal. This is more pronounced in the magnocellular pathway, which is much better suited to transmit the detailed structure of natural scenes than the parvocellular pathway. Whitening is less important for chromatic channels. Taken together, this shows how a complex interplay across space, time and spectral content sculpts ganglion cell responses.

Random Wiring, Ganglion Cell Mosaics, and the Functional Architecture of the Visual Cortex.

The architecture of iso-orientation domains in the primary visual cortex (V1) of placental carnivores and primates apparently follows species invariant quantitative laws. Dynamical optimization models assuming that neurons coordinate their stimulus preferences throughout cortical circuits linking millions of cells specifically predict these invariants. This might indicate that V1's intrinsic connectome and its functional architecture adhere to a single optimization principle with high precision and robustness. To validate this hypothesis, it is critical to closely examine the quantitative predictions of alternative candidate theories. Random feedforward wiring within the retino-cortical pathway represents a conceptually appealing alternative to dynamical circuit optimization because random dimension-expanding projections are believed to generically exhibit computationally favorable properties for stimulus representations. Here, we ask whether the quantitative invariants of V1 architecture can be explained as a generic emergent property of random wiring. We generalize and examine the stochastic wiring model proposed by Ringach and coworkers, in which iso-orientation domains in the visual cortex arise through random feedforward connections between semi-regular mosaics of retinal ganglion cells (RGCs) and visual cortical neurons. We derive closed-form expressions for cortical receptive fields and domain layouts predicted by the model for perfectly hexagonal RGC mosaics. Including spatial disorder in the RGC positions considerably changes the domain layout properties as a function of disorder parameters such as position scatter and its correlations across the retina. However, independent of parameter choice, we find that the model predictions substantially deviate from the layout laws of iso-orientation domains observed experimentally. Considering random wiring with the currently most realistic model of RGC mosaic layouts, a pairwise interacting point process, the predicted layouts remain distinct from experimental observations and resemble Gaussian random fields. We conclude that V1 layout invariants are specific quantitative signatures of visual cortical optimization, which cannot be explained by generic random feedforward-wiring models.

Data science and its future in large neuroscience collaborations.

The rise of large scientific collaborations in neuroscience requires systematic, scalable, and reliable data management. How this is best done in practice remains an open question. To address this, we conducted a data science survey among currently active U19 grants, funded through the NIH's BRAIN Initiative. The survey was answered by both data science liaisons and Principal Investigators, speaking for ~500 researchers across 21 nation-wide collaborations. We describe the tools, technologies, and methods currently in use, and identify several shortcomings of current data science practice. Building on this survey, we develop plans and propose policies to improve data collection, use, publication, reuse and training in the neuroscience community.

Data science and its future in large neuroscience collaborations.

Collaborative neuroscience requires systematic data management and analysis. How this is best done in practice remains unclear. Based on a survey across collaborative neuroscience projects, we document the current state of the art focusing on data integration, sharing, and researcher training. We propose best practices and list actions and policies to attain these goals.

TWINKLE: An open-source two-photon microscope for teaching and research.

Many laboratories use two-photon microscopy through commercial suppliers, or homemade designs of considerable complexity. The integrated nature of these systems complicates customization, troubleshooting as well as grasping the principles of two-photon microscopy. Here, we present "Twinkle": a microscope for Two-photon Imaging in Neuroscience, and Kit for Learning and Education. It is a fully open, high-performance and cost-effective research and teaching microscope without any custom parts beyond what can be fabricated in a university machine shop. The instrument features a large field of view, using a modern objective with a long working distance and large back aperture to maximize the fluorescence signal. We document our experiences using this system as a teaching tool in several two week long workshops, exemplify scientific use cases, and conclude with a broader note on the place of our work in the growing space of open-source scientific instrumentation.

Open Data In Neurophysiology: Advancements, Solutions & Challenges.

Across the life sciences, an ongoing effort over the last 50 years has made data and methods more reproducible and transparent. This openness has led to transformative insights and vastly accelerated scientific progress1,2. For example, structural biology3 and genomics4,5 have undertaken systematic collection and publication of protein sequences and structures over the past half-century, and these data have led to scientific breakthroughs that were unthinkable when data collection first began (e.g.6). We believe that neuroscience is poised to follow the same path, and that principles of open data and open science will transform our understanding of the nervous system in ways that are impossible to predict at the moment. To this end, new social structures along with active and open scientific communities are essential7 to facilitate and expand the still limited adoption of open science practices in our field8. Unified by shared values of openness, we set out to organize a symposium for Open Data in Neuroscience (ODIN) to strengthen our community and facilitate transformative neuroscience research at large. In this report, we share what we learned during this first ODIN event. We also lay out plans for how to grow this movement, document emerging conversations, and propose a path toward a better and more transparent science of tomorrow.

Neural circuit models for evidence accumulation through choice-selective sequences.

Decision making is traditionally thought to be mediated by populations of neurons whose firing rates persistently accumulate evidence across time. However, recent decision-making experiments in rodents have observed neurons across the brain that fire sequentially as a function of spatial position or time, rather than persistently, with the subset of neurons in the sequence depending on the animal's choice. We develop two new candidate circuit models, in which evidence is encoded either in the relative firing rates of two competing chains of neurons or in the network location of a stereotyped pattern ("bump") of neural activity. Encoded evidence is then faithfully transferred between neuronal populations representing different positions or times. Neural recordings from four different brain regions during a decision-making task showed that, during the evidence accumulation period, different brain regions displayed tuning curves consistent with different candidate models for evidence accumulation. This work provides mechanistic models and potential neural substrates for how graded-value information may be precisely accumulated within and transferred between neural populations, a set of computations fundamental to many cognitive operations.

PVP1-The People's Ventilator Project: A fully open, low-cost, pressure-controlled ventilator research platform compatible with adult and pediatric uses.

Mechanical ventilators are safety-critical devices that help patients breathe, commonly found in hospital intensive care units (ICUs)-yet, the high costs and proprietary nature of commercial ventilators inhibit their use as an educational and research platform. We present a fully open ventilator device-The People's Ventilator: PVP1-with complete hardware and software documentation including detailed build instructions and a DIY cost of $1,700 USD. We validate PVP1 against both key performance criteria specified in the U.S. Food and Drug Administration's Emergency Use Authorization for Ventilators, and in a pediatric context against a state-of-the-art commercial ventilator. Notably, PVP1 performs well over a wide range of test conditions and performance stability is demonstrated for a minimum of 75,000 breath cycles over three days with an adult mechanical test lung. As an open project, PVP1 can enable future educational, academic, and clinical developments in the ventilator space.

Orientation Preference Maps in Microcebus murinus Reveal Size-Invariant Design Principles in Primate Visual Cortex.

Orientation preference maps (OPMs) are a prominent feature of primary visual cortex (V1) organization in many primates and carnivores. In rodents, neurons are not organized in OPMs but are instead interspersed in a "salt and pepper" fashion, although clusters of orientation-selective neurons have been reported. Does this fundamental difference reflect the existence of a lower size limit for orientation columns (OCs) below which they cannot be scaled down with decreasing V1 size? To address this question, we examined V1 of one of the smallest living primates, the 60-g prosimian mouse lemur (Microcebus murinus). Using chronic intrinsic signal imaging, we found that mouse lemur V1 contains robust OCs, which are arranged in a pinwheel-like fashion. OC size in mouse lemurs was found to be only marginally smaller compared to the macaque, suggesting that these circuit elements are nearly incompressible. The spatial arrangement of pinwheels is well described by a common mathematical design of primate V1 circuit organization. In order to accommodate OPMs, we found that the mouse lemur V1 covers one-fifth of the cortical surface, which is one of the largest V1-to-cortex ratios found in primates. These results indicate that the primate-type visual cortical circuit organization is constrained by a size limitation and raises the possibility that its emergence might have evolved by disruptive innovation rather than gradual change.

The Synaptic Vesicle Priming Protein CAPS-1 Shapes the Adaptation of Sensory Evoked Responses in Mouse Visual Cortex.

Short-term plasticity gates information transfer across neuronal synapses and is thought to be involved in fundamental brain processes, such as cortical gain control and sensory adaptation. Neurons employ synaptic vesicle priming proteins of the CAPS and Munc13 families to shape short-term plasticity in vitro, but the relevance of this phenomenon for information processing in the intact brain is unknown. By combining sensory stimulation with in vivo patch-clamp recordings in anesthetized mice, we show that genetic deletion of CAPS-1 in thalamic neurons results in more rapid adaptation of sensory-evoked subthreshold responses in layer 4 neurons of the primary visual cortex. Optogenetic experiments in acute brain slices further reveal that the enhanced adaptation is caused by more pronounced short-term synaptic depression. Our data indicate that neurons engage CAPS-family priming proteins to shape short-term plasticity for optimal sensory information transfer between thalamic and cortical neurons in the intact brain in vivo.

Gender bias in scholarly peer review.

Peer review is the cornerstone of scholarly publishing and it is essential that peer reviewers are appointed on the basis of their expertise alone. However, it is difficult to check for any bias in the peer-review process because the identity of peer reviewers generally remains confidential. Here, using public information about the identities of 9000 editors and 43000 reviewers from the Frontiers series of journals, we show that women are underrepresented in the peer-review process, that editors of both genders operate with substantial same-gender preference (homophily), and that the mechanisms of this homophily are gender-dependent. We also show that homophily will persist even if numerical parity between genders is reached, highlighting the need for increased efforts to combat subtler forms of gender bias in scholarly publishing.

Growing neuronal islands on multi-electrode arrays using an accurate positioning-µCP device.

BACKGROUND: Multi-electrode arrays (MEAs) allow non-invasive multi-unit recording in-vitro from cultured neuronal networks. For sufficient neuronal growth and adhesion on such MEAs, substrate preparation is required. Plating of dissociated neurons on a uniformly prepared MEA's surface results in the formation of spatially extended random networks with substantial inter-sample variability. Such cultures are not optimally suited to study the relationship between defined structure and dynamics in neuronal networks. To overcome these shortcomings, neurons can be cultured with pre-defined topology by spatially structured surface modification. Spatially structuring a MEA surface accurately and reproducibly with the equipment of a typical cell-culture laboratory is challenging. NEW METHOD: In this paper, we present a novel approach utilizing micro-contact printing (µCP) combined with a custom-made device to accurately position patterns on MEAs with high precision. We call this technique AP-µCP (accurate positioning micro-contact printing). COMPARISON WITH EXISTING METHODS: Other approaches presented in the literature using µCP for patterning either relied on facilities or techniques not readily available in a standard cell culture laboratory, or they did not specify means of precise pattern positioning. CONCLUSION: Here we present a relatively simple device for reproducible and precise patterning in a standard cell-culture laboratory setting. The patterned neuronal islands on MEAs provide a basis for high throughput electrophysiology to study the dynamics of single neurons and neuronal networks.

Can retinal ganglion cell dipoles seed iso-orientation domains in the visual cortex?

It has been argued that the emergence of roughly periodic orientation preference maps (OPMs) in the primary visual cortex (V1) of carnivores and primates can be explained by a so-called statistical connectivity model. This model assumes that input to V1 neurons is dominated by feed-forward projections originating from a small set of retinal ganglion cells (RGCs). The typical spacing between adjacent cortical orientation columns preferring the same orientation then arises via Moiré-Interference between hexagonal ON/OFF RGC mosaics. While this Moiré-Interference critically depends on long-range hexagonal order within the RGC mosaics, a recent statistical analysis of RGC receptive field positions found no evidence for such long-range positional order. Hexagonal order may be only one of several ways to obtain spatially repetitive OPMs in the statistical connectivity model. Here, we investigate a more general requirement on the spatial structure of RGC mosaics that can seed the emergence of spatially repetitive cortical OPMs, namely that angular correlations between so-called RGC dipoles exhibit a spatial structure similar to that of OPM autocorrelation functions. Both in cat beta cell mosaics as well as primate parasol receptive field mosaics we find that RGC dipole angles are spatially uncorrelated. To help assess the level of these correlations, we introduce a novel point process that generates mosaics with realistic nearest neighbor statistics and a tunable degree of spatial correlations of dipole angles. Using this process, we show that given the size of available data sets, the presence of even weak angular correlations in the data is very unlikely. We conclude that the layout of ON/OFF ganglion cell mosaics lacks the spatial structure necessary to seed iso-orientation domains in the primary visual cortex.

Frequency-dependent signal transfer at the interface between electrogenic cells and nanocavity electrodes.

We present a model to describe the response of chip-based nanocavity sensors during extracellular recording of action potentials. These sensors feature microelectrodes which are embedded in liquid-filled cavities. They can be used for the highly localized detection of electrical signals on a chip. We calculate the sensor's impedance and simulate the propagation of action potentials. Subsequently we apply our findings to analyze cell-chip coupling properties. The results are compared to experimental data obtained from cardiomyocyte-like cells. We show that both the impedance and the modeled action potentials fit the experimental data well. Furthermore, we find evidence for a large seal resistance of cardiomyocytes on nanocavity sensors compared to conventional planar recording systems.

Nanocavity electrode array for recording from electrogenic cells.

We present a new nanocavity device for highly localized on-chip recordings of action potentials from individual cells in a network. Microelectrode recordings have become the method of choice for recording extracellular action potentials from high density cultures or slices. Nevertheless, interfacing individual cells of a network with high resolution still remains challenging due to an insufficient coupling of the signal to small electrodes, exhibiting diameters below 10 µm. We show that this problem can be overcome by a new type of sensor that features an electrode, which is accessed via a small aperture and a nanosized cavity. Thus, the properties of large electrodes are combined with a high local resolution and a good seal resistance at the interface. Fabrication of the device can be performed with state-of-the-art clean room technology and sacrificial layer etching allowing integration of the devices into sensor arrays. We demonstrate the capability of such an array by recording the propagation of action potentials in a network of cardiomyocyte-like cells.