Kavli NDI serves as a central hub to initiate and foster collaborations within the three 'Pillars of Innovation'—NeuroExperiments, NeuroEngineering, and NeuroData—to catalyze discoveries that deepen our understanding of the brain's structure and function.
This beautiful image that resembles a flower is a structure called retina that lines the inner wall of the eye. Specialized cells called photoreceptors, transmit light that enters the eyes to the optic nerve. Retina is richly innervated by blood vessels (purple). Learn more about the role of retina in the visual processing here. This beautiful image that resembles a flower is a structure called retina that lines the inner wall of the eye. Specialized cells called photoreceptors, transmit light that enters the eyes to the optic nerve. Retina is richly innervated by blood vessels (purple). Learn more about the role of retina in the visual processing here. Image Curtsey: Alex Kolodkin Image Curtsey: Alex Kolodkin
Axonal innervation of the retinal ganglion cell to the superior colliculus and their postsynaptic targets, labeled via a wheat germ agglutinin virus
The somatosensory cortex is organized into distinct cortical layers. Layer II/III neurons extend collateral axon branches mainly in layers II/III and V. In this image, newly developed sparse (red) and bulk (green) labeling techniques were used to evaluate the branching patterns of single layer II/III neurons amongst the greater population of cortical projection neurons. Visualizing individual collateral branches is crucial for understanding the molecular mechanisms that drive their patterning in healthy and disease states. See the manuscript by Dorskind et al. (J. Neurosci., 2023) for more information (Image: Joelle Dorskind).
Kavli NDI PI, Alex Kolodkin is interested in understanding how neuronal connections are established during development. The lab investigates the role of extrinsic cues in axon guidance, determination of dendritic morphology and in the establishment and maintenance of neuronal connectivity. In a study reported in Elife the team has recently shown that signaling mediated by Semaphorins and their receptors Nrp1 and Nrp2 is crucial for regulating the morphology of dendritic spines and dendritic arborization during development.
A crucial factor for the establishment of cortical circuitry is laminar-specific axon targeting. In a separate study, the group,using custom molecular tools, hasshown that the cytoskeletal protein drebrin (Dbn1) regulates excitatory Layer II/III cortical projection neuron (CPN) collateral axon branching, thereby identifying the molecular underpinnings of laminar specific innervation of axons terminals.
The lab is specifically interested in the wiring diagram of the visual system, the connections between theretinal ganglion cell (RGC) axons and their central targets in the brain. The team has recently demonstrated the role played by a protein Tenm3 in the establishment of retinal circuitry.
Kavli NDI PI Dingchang Lin leverages multidisciplinary expertise in chemistry, materials synthesis, protein engineering, and micro/nanofabrication, toaddress existing technological challenges in neuroscience research. The research emphasisencompasses molecular, device, and systems levels, allowing us to develop comprehensive solutions across scales. At the molecular level, the Lin Lab combines protein design and evolutionary methods to create intracellular memory devices that record brain-wide neuronal dynamics with cellular resolution. Specifically, the team focuses on engineering intracellular recorders that capture the histories of neural activity within individual cells, enabling retrospective readout of neural events. At the device level,the Lin Lab develops tissue-mimeticultraflexible neural probes that seamlessly interface with the brain. These probes are mechanicallysimilar tothe soft brain tissue, minimizing gliosis and facilitating chronic recording from the same neuronal population over extended periods. On the systems level, the Lin lab drives innovation in modalities and surgical apparatuses for the precise and minimally invasive delivery of drugs, genetic materials, and electronic devices to the brain. The ultimate goal of the Lin lab is to empower researchers with transformative tools and methodologies that enable deeper insights into the central nervous system, fostering advancements in both basic and applied neuroscience.
Reconstructed geometry of the hippocampus from postmortem high-field MRI aligned to Mai Paxinos Atlas coordinates with 2D digital pathology sections mapped to corresponding position in 3D geometry.
Alignment of BARseq-detected cells at micrometer scale in 2D coronal sections to Allen CCFv3 tissue scale atlas using image-varifold based LDDMM to achieve layer-by-layer alignment across the modalities within the six layers of cortex.
Neglecting the action of a nonlinear mapping on a curve's derivatives can introduce errors. a-b Different samplings of a curve can lead to different results under nonlinear deformations, such as only sampling the endpoints (a) versus sampling several times along the curve (b). c-d Large distances between trace points can contribute to mapping inaccuracies. The green line segment following cortical layers 2/3 in a synthetic mouse brain image (c) is defined only by its endpoints. Transforming only the positions of the endpoints (zeroth order mapping, (d), is less accurate than incorporating the action on the derivatives as well (first order mapping, d). e-f Quantitative descriptions of the mapping from target to atlas via the logarithm of the Jacobian determinant, which quantifies expansion and compression (e), and the spectral norm of the displacement field, which plays a role in an error bound of zeroth order mapping (f).
Recent engineering advancements have ushered in an era of unprecedented capability for acquiring vast amounts of neuroscience data. Kavli NDI is dedicated fostering research in mathematical and computational sciences, computing machinery, algorithms, and hardware architecture to translate extensive datasets into monumental breakthroughs and discoveries to understand the intricate structure and function of the nervous system.
Kavli NDI PI, Michael Miller is a biomedical engineer specializing in data science. Miller lab deploys next generation computational technologies to identifyneurodegenerative diseases including Huntington’s and Alzheimer’s disease. In a recent study, KavliNDI fellow Kaitlin Stouffer from the Miller Lab, highlighted a possible role for an emotion-related brain region called the amygdala in the progression of Alzheimer's disease (Link the interview and Brain MS). Image and legend. The lab also develops computational methodologies to map data across scales. The group recently developed a technique to link molecular measurements at micrometer scales to dense MRI measurements at tissue scale and is expanding their technologies now to map even higher dimensional data at submicrometer scales emerging in areas of spatial transcriptomics These techniques will have transformative impact, amongst other areas, on biomarker discoveries associated with neurodegenerative disease pathology. The group also develops computational algorithms to map axonal morphologies within the brain volume to construct high resolution, 3D atlases at the cellular level.