Frederick Federer

Four projection streams from primate V1 to the cytochrome oxidase stripes of V2

In the primate visual system, areas V1 and V2 distribute information they receive from the retina to all higher cortical areas, sorting this information into dorsal and ventral streams. Therefore, knowledge of the organization of projections between V1 and V2 is crucial to understand how the cortex processes visual information. In primates, parallel output pathways from V1 project to distinct V2 stripes. The traditional tripartite division of V1-to-V2 projections was recently replaced by a bipartite scheme, in which thin stripes receive V1 inputs from blob columns, and thick and pale stripes receive common input from interblob columns. Here, we demonstrate that thick and pale stripes, instead, receive spatially segregated V1 inputs and that the interblob is partitioned into two compartments: the middle of the interblob projecting to pale stripes and the blob/interblob border region projecting to thick stripes. Double-labeling experiments further demonstrate that V1 cells project to either thick or pale stripes, but rarely to both. We also find laminar specialization of V1 outputs, with layer 4B contributing projections mainly to thick stripes, and no projections to one set of pale stripes. These laminar differences suggest different contribution of magno, parvo, and konio inputs to each V1 output pathway. These results provide a new foundation for parallel processing models of the visual system by demonstrating four V1-to-V2 pathways: blob columns-to-thin stripes, blob/interblob border columns-to-thick stripes, interblob columns-to-palelateral stripes, layer 2/3–4A interblobs-to-palemedial stripes.

Circuits and Mechanisms for Surround Modulation in Visual Cortex

Surround modulation (SM) is a fundamental property of sensory neurons in many species and sensory modalities. SM is the ability of stimuli in the surround of a neurons receptive field (RF) to modulate (typically suppress) the neurons response to stimuli simultaneously presented inside the RF, a property thought to underlie optimal coding of sensory information and important perceptual functions. Understanding the circuit and mechanisms for SM can reveal fundamental principles of computations in sensory cortices, from mouse to human. Current debate is centered over whether feedforward or intracortical circuits generate SM, and whether this results from increased inhibition or reduced excitation. Here we present a working hypothesis, based on theoretical and experimental evidence, that SM results from feedforward, horizontal, and feedback interactions with local recurrent connections, via synaptic mechanisms involving both increased inhibition and reduced recurrent excitation. In particular, strong and balanced recurrent excitatory and inhibitory circuits play a crucial role in the computation of SM.

Two projection streams from macaque V1 to the pale cytochrome oxidase stripes of V2

In the primate visual cortex, areas V1 and V2 distribute information they receive from the retina to virtually all extrastriate cortex, parsing this information into dorsal and ventral streams. Therefore, understanding the connectivity between V1 and V2 is crucial to understand visual cortical processing. Cytochrome oxidase staining in V2 reveals a repeating pattern of pale–thick–pale–thin stripes. V1 sends parallel output pathways to distinct V2 stripes. Previous models proposed either three or two parallel V1-to-V2 pathways in macaque, but both models viewed the two pale stripes within a single stripe cycle as a single compartment. However, recent studies have suggested that the two pale stripes may be functionally distinct, and in marmosets they also differ anatomically in the laminar origin of projections they receive from V1. Here we have asked whether the two pale stripes are also anatomically distinct in macaque. We made small retrograde tracer injections in different pale stripe types. We found that while both pale stripes receive a predominant V1 input from layers 2/3, only one set of pale stripes (pale lateral) receives significant projections from layer 4B, while the other set (pale medial) receives few or no layer 4B projections. Moreover, different tracer injections in nearby pale stripe types revealed that 97–99% of layer 2/3 cells only project to a single pale stripe type. These results demonstrate that in macaque, the two pale stripes are anatomically distinct compartments, and support the notion of two distinct projection streams from V1 to the two pale stripes of V2.

A Virtual Reality Visualization Tool for Neuron Tracing

Tracing neurons in large-scale microscopy data is crucial to establishing a wiring diagram of the brain, which is needed to understand how neural circuits in the brain process information and generate behavior. Automatic techniques often fail for large and complex datasets, and connectomics researchers may spend weeks or months manually tracing neurons using 2D image stacks. We present a design study of a new virtual reality (VR) system, developed in collaboration with trained neuroanatomists, to trace neurons in microscope scans of the visual cortex of primates. We hypothesize that using consumer-grade VR technology to interact with neurons directly in 3D will help neuroscientists better resolve complex cases and enable them to trace neurons faster and with less physical and mental strain. We discuss both the design process and technical challenges in developing an interactive system to navigate and manipulate terabyte-sized image volumes in VR. Using a number of different datasets, we demonstrate that, compared to widely used commercial software, consumer-grade VR presents a promising alternative for scientists.

Top-down feedback controls spatial summation and response amplitude in primate visual cortex

Sensory information travels along feedforward connections through a hierarchy of cortical areas, which, in turn, send feedback connections to lower-order areas. Feedback has been implicated in attention, expectation, and sensory context, but the mechanisms underlying these diverse feedback functions are unknown. Using specific optogenetic inactivation of feedback connections from the secondary visual area (V2), we show how feedback affects neural responses in the primate primary visual cortex (V1). Reducing feedback activity increases V1 cells’ receptive field (RF) size, decreases their responses to stimuli confined to the RF, and increases their responses to stimuli extending into the proximal surround, therefore reducing surround suppression. Moreover, stronger reduction of V2 feedback activity leads to progressive increase in RF size and decrease in response amplitude, an effect predicted by a recurrent network model. Our results indicate that feedback modulates RF size, surround suppression and response amplitude, similar to the modulatory effects of visual spatial attention.Feedback modulation of V1 is implicated in functions such as attention yet the precise neural mechanisms are not known. Here the authors report that optogenetic inactivation of V2 projections leads to modulation of V1 receptive field properties such as size, surround suppression and response amplitude.

Corticocortical connection patterns reveal two distinct visual cortical areas bordering dorsal V2 in marmoset monkey

The organization of the cortex located immediately anterior to the second visual area (V2), i.e., the third tier visual cortex, remains controversial, especially in New World primates. In particular, there is lack of consensus regarding the exact location and extent of the lower visual quadrant representation of the third visual area V3 (or ventrolateral posterior –VLP – of a different nomenclature). Microelectrode and connectional mapping studies have revealed the existence of an upper visual quadrant representation abutting dorsal V2 anteriorly, and bordered medially and laterally by representations of the lower visual quadrant. It remains unclear whether these lower field regions are both part of a single area V3, which is split into two patches by an interposed region of upper field representation, or whether they are the lower field representations of two different areas, the dorsomedial area (DM) and area V3/VLP, respectively. To address this question, we quantitatively analyzed the patterns of corticocortical afferent connections labeled by tracer injections targeted to these two lower field regions in the dorsal aspect of the third tier cortex. We found different inter-areal connectivity patterns arising from these two regions, strongly suggesting that they belong to two different visual areas. In particular, our results indicate that the dorsal aspect of the third tier cortex consists of two distinct areas: a full area DM, representing the lower quadrant medially, and the upper quadrant laterally, and the lower quadrant representation of V3/VLP, located laterally to upper field DM. DM is predominantly connected with areas of the dorsal visual stream, and V3/VLP with areas of the ventral stream. These results prompt further functional investigations of the third tier cortex, as previous studies of this cortical territory may have pooled response properties of two very different areas into a single area V3.

ISAVS: interactive scalable analysis and visualization system

Modern science is inundated with ever increasing data sizes as computational capabilities and image acquisition techniques continue to improve. For example, simulations are tackling ever larger domains with higher fidelity, and high-throughput microscopy techniques generate larger data that are fundamental to gather biologically and medically relevant insights. As the image sizes exceed memory, and even sometimes local disk space, each step in a scientific workflow is impacted. Current software solutions enable data exploration with limited interactivity for visualization and analytic tasks. Furthermore analysis on HPC systems often require complex hand-written parallel implementations of algorithms that suffer from poor portability and maintainability. We present a software infrastructure that simplifies end-to-end visualization and analysis of massive data. First, a hierarchical streaming data access layer enables interactive exploration of remote data, with fast data fetching to test analytics on subsets of the data. Second, a library simplifies the process of developing new analytics algorithms, allowing users to rapidly prototype new approaches and deploy them in an HPC setting. Third, a scalable runtime system automates mapping analysis algorithms to whatever computational hardware is available, reducing the complexity of developing scaling algorithms. We demonstrate the usability and performance of our system using a use case from neuroscience: filtering, registration, and visualization of tera-scale microscopy data. We evaluate the performance of our system using a leadership-class supercomputer, Shaheen II.

CORTICO-CORTICAL FEEDBACK CONTROLS SPATIAL SUMMATION IN PRIMATE VISUAL CORTEX

Our visual perception of the external world relies on neural activity across a hierarchy of visual cortical areas, communicating via complex feedforward-feedback pathways. While feedforward pathways have been a focus of study, the role of the feedback pathway has remained poorly understood. Here we have developed a novel viral vector combination allowing for selective optogenetic inactivation of feedback pathways in the non-human primate brain. We show that even the most fundamental response properties of visual neurons, such as the receptive field size, are regulated by feedback signals from other regions of the visual cortex. Depending on its activity regime, cortico-cortical feedback can regulate receptive field size and contextual modulation of visual responses or the overall response gain of neurons.In the cerebral cortex, sensory information travels along feedforward connections through a hierarchy of areas processing increasingly complex stimulus features1. Hierarchical processing, based solely on feedforward connections, has dominated most theories of sensory processing in neuroscience and computer vision over the past 50 years2,3. These theories, however, have disregarded the existence of anatomically more prominent feedback connections from higher- to lower-order cortical areas1, whose function remains hypothetical. Feedback has been implicated in attention4,5, expectation6, and sensory context7,8, but the cellular mechanisms underlying these diverse feedback functions are unknown. Moreover, it is controversial whether feedback modulates response gain9-12 or surround suppression13-15 (the modulatory influence of sensory context on neuronal responses16-19) in lower-order areas. Here we have performed the first specific inactivation of cortical feedback at millisecond-time resolution, by optogenetically inactivating feedback connections from the secondary (V2) to the primary visual cortex (V1) in primates. Moderate reduction of V2 feedback activity increased RF size and reduced surround suppression in V1, while strongly reducing feedback activity decreased response gain. Our study has identified a small set of fundamental operations as the cellular-level mechanisms of feedback-mediated top down modulations of early sensory processing. These operations allow the visual system to dynamically regulate spatial resolution, by changing RF size, its sensitivity to image features, by changing response gain, and efficiency of coding natural images, by providing surround suppression.

A scalable cyberinfrastructure for interactive visualization of terascale microscopy data

The goal of the recently emerged field of connectomics is to generate a wiring diagram of the brain at different scales. To identify brain circuitry, neuroscientists use specialized microscopes to perform multichannel imaging of labeled neurons at a very high resolution. CLARITY tissue clearing allows imaging labeled circuits through entire tissue blocks, without the need for tissue sectioning and section-to-section alignment. Imaging the large and complex non-human primate brain with sufficient resolution to identify and disambiguate between axons, in particular, produces massive data, creating great computational challenges to the study of neural circuits. Researchers require novel software capabilities for compiling, stitching, and visualizing large imagery. In this work, we detail the image acquisition process and a hierarchical streaming platform, ViSUS, that enables interactive visualization of these massive multi-volume datasets using a standard desktop computer. The ViSUS visualization framework has previously been shown to be suitable for 3D combustion simulation, climate simulation and visualization of large scale panoramic images. The platform is organized around a hierarchical cache oblivious data layout, called the IDX file format, which enables interactive visualization and exploration in ViSUS, scaling to the largest 3D images. In this paper we showcase the VISUS framework used in an interactive setting with the microscopy data.