Faculty Bibliography

In the mammalian visual system, early stages of visual form processing begin with orientation-selective neurons in primary visual cortex (V1). In many species (including humans, monkeys, tree shrews, cats, and ferrets), these neurons are organized in a beautifully arrayed pinwheel-like orientation columns, which shift in orientation preference across V1. However, to date, the relationship of orientation architecture to the encoding of multiple elemental aspects of visual contours is still unknown. Here, using a novel, highly accurate method of targeting electrode position, we report for the first time the presence of three subdomains within single orientation domains. We suggest that these zones subserve computation of distinct aspects of visual contours and propose a novel tripartite pinwheel-centered view of an orientation hypercolumn.

We have developed a way to map brain-wide networks using focal pulsed infrared neural stimulation in ultrahigh-field magnetic resonance imaging (MRI). The patterns of connections revealed are similar to those of connections previously mapped with anatomical tract tracing methods. These include connections between cortex and subcortical locations and long-range cortico-cortical connections. Studies of local cortical connections reveal columnar-sized laminar activation, consistent with feed-forward and feedback projection signatures. This method is broadly applicable and can be applied to multiple areas of the brain in different species and across different MRI platforms. Systematic point-by-point application of this method may lead to fundamental advances in our understanding of brain connectomes.

Functions of the cerebral cortex emerge via interactions of horizontally distributed neuronal populations within and across areas. However, the connectional underpinning of these interactions is not well understood. The present study explores the circuitry of column-size cortical domains within the hierarchically organized somatosensory cortical areas 3b and 1 using tract tracing and optical intrinsic signal imaging (OIS). The anatomical findings reveal that feedforward connections exhibit high topographic specificity, while intrinsic and feedback connections have a more widespread distribution. Both intrinsic and inter-areal connections are topographically oriented across the finger representations. Compared to area 3b, the low clustering of connections and small cortical magnification factor supports that the circuitry of area 1 scaffolds a sparse functional representation that integrates peripheral information from a large area that is fed back to area 3b. Fast information exchange between areas is ensured by thick axons forming a topographically organized, reciprocal pathway. Moreover, the highest density of projecting neurons and groups of axon arborization patches corresponds well with the size and locations of the functional population response reported by OIS. The findings establish connectional motifs at the mesoscopic level that underpin the functional organization of the cerebral cortex.

In primates, visual perception is mediated by brain circuits composed of submillimeter nodes linked together in specific networks that process different types of information, such as eye specificity and contour orientation. We hypothesized that optogenetic stimulation targeted to cortical nodes could selectively activate such cortical networks. We used viral transfection methods to confer light sensitivity to neurons in monkey primary visual cortex. Using intrinsic signal optical imaging and single-unit electrophysiology to assess effects of targeted optogenetic stimulation, we found that (i) optogenetic stimulation of single ocular dominance columns (eye-specific nodes) revealed preferential activation of nearby same-eye columns but not opposite-eye columns, and (ii) optogenetic stimulation of single orientation domains increased visual response of matching orientation domains and relatively suppressed nonmatching orientation selectivity. These findings demonstrate that optical stimulation of single nodes leads to modulation of functionally specific cortical networks related to underlying neural architecture.

Deep-tissue imaging is of great significance to biological applications. In this paper, a deep-red emissive luminogen 2,3-bis(4'-(diphenylamino)-[1,1'-biphenyl]-4-yl) fumaronitrile (TPATCN) with aggregation-induced emission (AIE) feature is prepared. TPATCN molecules were then encapsulated within a polymeric matrix of Pluronic F-127 to form nanoparticles (NPs). TPATCN NPs exhibit bright three-photon fluorescence (3PF) in deep-red region, together with high chemical stability, good photostability, and biocompatibility. They are further utilized for in vivo 3PF imaging of the brain vasculature of mice, under the excitation of a 1550 nm femtosecond laser. A vivid 3D reconstruction of the brain vasculature is then built with a penetration depth of 875 µm, which is the largest in ever reported 3PF imaging based on AIE NPs. After that, by collecting both of the 3PF and third-harmonic generation signals, multichannel nonlinear optical imaging of the brain blood vessels is further realized. These results will be helpful to study the structures and functions of the brain in the future.