Conserved transcriptional regulation by BRN1 and BRN2 in neocortical progenitors drives mammalian neural specification and neocortical expansion.

The neocortex varies in size and complexity among mammals due to the tremendous variability in the number and diversity of neuronal subtypes across species. The increased cellular diversity is paralleled by the expansion of the pool of neocortical progenitors and the emergence of indirect neurogenesis during brain evolution. The molecular pathways that control these biological processes and are disrupted in neurological disorders remain largely unknown.

The Cousa objective: a long-working distance air objective for multiphoton imaging in vivo.

Multiphoton microscopy can resolve fluorescent structures and dynamics deep in scattering tissue and has transformed neural imaging, but applying this technique in vivo can be limited by the mechanical and optical constraints of conventional objectives. Short working distance objectives can collide with compact surgical windows or other instrumentation and preclude imaging. Here we present an ultra-long working distance (20 mm) air objective called the Cousa objective.

Object representation in a gravitational reference frame.

When your head tilts laterally, as in sports, reaching, and resting, your eyes counterrotate less than 20%, and thus eye images rotate, over a total range of about 180°. Yet, the world appears stable and vision remains normal. We discovered a neural strategy for rotational stability in anterior inferotemporal cortex (IT), the final stage of object vision in primates.

Cell-specific regulation of gene expression using splicing-dependent frameshifting.

Precise and reliable cell-specific gene delivery remains technically challenging. Here we report a splicing-based approach for controlling gene expression whereby separate translational reading frames are coupled to the inclusion or exclusion of mutated, frameshifting cell-specific alternative exons. Candidate exons are identified by analyzing thousands of publicly available RNA sequencing datasets and filtering by cell specificity, conservation, and local intron length.

Development of visual motion integration involves coordination of multiple cortical stages.

A central feature of cortical function is hierarchical processing of information. Little is currently known about how cortical processing cascades develop. Here, we investigate the joint development of two nodes of the ferret's visual motion pathway, primary visual cortex (V1), and higher-level area PSS.

Early Emergence of Solid Shape Coding in Natural and Deep Network Vision.

Area V4 is the first object-specific processing stage in the ventral visual pathway, just as area MT is the first motion-specific processing stage in the dorsal pathway. For almost 50 years, coding of object shape in V4 has been studied and conceived in terms of flat pattern processing, given its early position in the transformation of 2D visual images. Here, however, in awake monkey recording experiments, we found that roughly half of V4 neurons are more tuned and responsive to solid, 3D shape-in-depth, as conveyed by shading, specularity, reflection, refraction, or disparity cues in images.

Advanced Circuit and Cellular Imaging Methods in Nonhuman Primates.

Novel genetically encoded tools and advanced microscopy methods have revolutionized neural circuit analyses in insects and rodents over the last two decades. Whereas numerous technical hurdles originally barred these methodologies from success in nonhuman primates (NHPs), current research has started to overcome those barriers. In some cases, methodological advances developed with NHPs have even surpassed their precursors.

Visual Motion and Form Integration in the Behaving Ferret.

Ferrets have become a standard animal model for the development of early visual stages. Less is known about higher-level vision in ferrets, both during development and in adulthood. Here, as a step towards establishing higher-level vision research in ferrets, we used behavioral experiments to test the motion and form integration capacity of adult ferrets.

Ferrets as a Model for Higher-Level Visual Motion Processing.

Ferrets are a major developmental animal model due to their early parturition. Here we show for the first time that ferrets could be used to study development of higher-level visual processes previously identified in primates. In primates, complex motion processing involves primary visual cortex (V1), which generates local motion signals, and higher-level visual area MT, which integrates these signals over more global spatial regions.

Efficient Receptive Field Tiling in Primate V1.

The primary visual cortex (V1) encodes a diverse set of visual features, including orientation, ocular dominance (OD), and spatial frequency (SF), whose joint organization must be precisely structured to optimize coverage within the retinotopic map. Prior experiments have only identified efficient coverage based on orthogonal maps. Here we used two-photon calcium imaging to reveal an alternative arrangement for OD and SF maps in macaque V1; their gradients run parallel but with unique spatial periods, whereby low-SF regions coincide with monocular regions.

Building maps from maps in primary visual cortex.

Neurons in the visual system respond to more complex and holistic features at each new stage of processing. Often, these features are organized into continuous maps. Could there be a fundamental link between continuous maps and functional hierarchies? Here, we review recent studies regarding V1 maps providing some of the most noteworthy advances in our understanding of how and why maps exist.

Orthogonal micro-organization of orientation and spatial frequency in primate primary visual cortex.

Orientation and spatial frequency tuning are highly salient properties of neurons in primary visual cortex (V1). The combined organization of these particular tuning properties in the cortical space will strongly shape the V1 population response to different visual inputs, yet it is poorly understood. In this study, we used two-photon imaging in macaque monkey V1 to demonstrate the three-dimensional cell-by-cell layout of both spatial frequency and orientation tuning.

Viral vector-based reversible neuronal inactivation and behavioral manipulation in the macaque monkey.

Viral vectors are promising tools for the dissection of neural circuits. In principle, they can manipulate neurons at a level of specificity not otherwise achievable. While many studies have used viral vector-based approaches in the rodent brain, only a few have employed this technique in the non-human primate, despite the importance of this animal model for neuroscience research.

Nonlinearity of two-photon Ca2+ imaging yields distorted measurements of tuning for V1 neuronal populations.

We studied the relative accuracy of drifting gratings and noise stimuli for functionally characterizing neural populations using two-photon calcium imaging. Calcium imaging has the potential to distort measurements due to nonlinearity in the conversion from spikes to observed fluorescence. We demonstrate a dramatic impact of fluorescence saturation on functional measurements in ferret V1 by showing that responses to drifting gratings strongly violate contrast invariance of orientation tuning, a fundamental property of the spike rates.

Targeting single neuronal networks for gene expression and cell labeling in vivo.

To understand fine-scale structure and function of single mammalian neuronal networks, we developed and validated a strategy to genetically target and trace monosynaptic inputs to a single neuron in vitro and in vivo. The strategy independently targets a neuron and its presynaptic network for specific gene expression and fine-scale labeling, using single-cell electroporation of DNA to target infection and monosynaptic retrograde spread of a genetically modifiable rabies virus. The technique is highly reliable, with transsynaptic labeling occurring in every electroporated neuron infected by the virus.

Object features used by humans and monkeys to identify rotated shapes.

Humans and rhesus monkeys can identify shapes that have been rotated in the picture plane. Recognition of rotated shapes can be as efficient as recognition of upright shapes. Here we investigate whether subjects showing view-invariant performance use the same object features to identify upright and rotated versions of a shape.

More than a feeling: sensation from cortical stimulation.

Changes in neuronal firing underlie sensation, but how many neurons are needed to perceive these activity shifts? Two new studies in Nature suggest that the experimental modulation of only a few neurons can influence perception.

Object recognition: similar visual strategies of birds and mammals.

Behavioral testing has revealed that pigeons may use the same visual information sources as humans to discriminate between three-dimensional shapes.

Dissociation between local field potentials and spiking activity in macaque inferior temporal cortex reveals diagnosticity-based encoding of complex objects.

Neurons in the inferior temporal (IT) cortex respond selectively to complex objects, and maintain their selectivity despite partial occlusion. However, relatively little is known about how the occlusion of different shape parts influences responses in the IT cortex. Here, we determine experimentally which parts of complex objects monkeys are relying on in a discrimination task.

Discrimination strategies of humans and rhesus monkeys for complex visual displays.

By learning to discriminate among visual stimuli, human observers can become experts at specific visual tasks. The same is true for Rhesus monkeys, the major animal model of human visual perception. Here, we systematically compare how humans and monkeys solve a simple visual task.

Fixations in natural scenes: interaction of image structure and image content.

Explorative eye movements specifically target some parts of a scene while ignoring others. Here, we investigate how local image structure--defined by spatial frequency contrast--and informative image content--defined by higher order image statistics-are weighted for the selection of fixation points. We measured eye movements of macaque monkeys freely viewing a set of natural and manipulated images outside a particular task.