Biology subjects

Jasanoff, A.

Publications and source records attributed to Jasanoff, A..

7 recordsLinked to original sources

bioRxiv2026

High-throughput light-sheet 3D microscopy of whole rodent brain microstructure for integration with MRI

Whole-brain cellular mapping is essential for understanding how differences in cellular architecture shape brain organisation and function. Magnetic Resonance Imaging (MRI) provides whole-brain coverage in humans and animal models but is only indirectly sensitive to cellular features. Integrating MRI with whole-brain microscopy is therefore critical for interpreting existing microstructural MRI metrics and developing new, more specific ones. Here, we present a scalable cross-resolution framework that integrates 3D light-sheet microscopy (LSM) of intact rodent brains with diffusion MRI (dMRI) to bridge cellular and macroscopic brain imaging. By combining active electrotransport-based tissue clearing and immunolabelling with accelerated LSM acquisitions, we achieve whole-brain multiplexed mapping of neuronal and glial populations in intact rodent brains on timescales comparable to conventional histology and 2D microscopy. This throughput enables LSM and MRI integration at scale, linking macroscopic MRI contrasts to microscopic cellular features within the same tissue. We apply this framework across eight genetically diverse mouse strains to develop predictive models of 3D microscopy-derived cellular features from multi-shell dMRI-derived contrasts. We demonstrate that data-driven combinations of state-of-the-art dMRI contrasts predict neuronal and astrocytic features better than individual contrasts, across all animals. Our novel approach enables 3D microscopy to guide the development and interpretation of microstructural MRI measures that are ultimately translatable to the living human brain.

neuroscience↗

bioRxiv2026

Transformation and recombination of neural information in a brain network

Mammalian brain function relies on integrated interactions among interconnected neural structures. The principles by which regional activity is transformed into projection-specific signals and then recombined at targets elsewhere in the brain are fundamental to brain processing, but remain poorly understood. Here we study these phenomena using a genetically encoded probe that provides neurophysiological readouts from virally labeled projections on a brain-wide scale via functional magnetic resonance imaging (fMRI). By analyzing outputs from thalamic and cortical somatosensory processing regions in rats, we find that projection-specific neural population activity undergoes shifts in tuning and temporal characteristics as it emanates from source regions. Patterns of neural information flow to targeted brain structures reconfigure under different conditions of stimulation and rest, contrasting with intrinsic fMRI functional connectivity profiles, which remain constant. Excitatory and inhibitory projections are coactivated during stimulation, but their relative response amplitudes change dynamically between stimulus conditions and across repeated stimuli, suggesting mechanistic roles for network-wide shifts in excitation/inhibition balance. Our results thus reveal how information flow throughout a neural system reshapes to promote stimulus selectivity and provide underpinnings of large-scale brain phenomena.

neuroscience↗

bioRxiv2024

Fiber-based Probes for Electrophysiology, Photometry, Optical and Electrical Stimulation, Drug Delivery, and Fast-Scan Cyclic Voltammetry In Vivo

Recording and modulation of neuronal activity enables the study of brain function in health and disease. While translational neuroscience relies on electrical recording and modulation techniques, mechanistic studies in rodent models leverage genetic precision of optical methods, such as optogenetics and imaging of fluorescent indicators. In addition to electrical signal transduction, neurons produce and receive diverse chemical signals which motivate tools to probe and modulate neurochemistry. Although the past decade has delivered a wealth of technologies for electrophysiology, optogenetics, chemical sensing, and optical recording, combining these modalities within a single platform remains challenging. This work leverages materials selection and convergence fiber drawing to permit neural recording, electrical stimulation, optogenetics, fiber photometry, drug and gene delivery, and voltammetric recording of neurotransmitters within individual fibers. Composed of polymers and non-magnetic carbon-based conductors, these fibers are compatible with magnetic resonance imaging, enabling concurrent stimulation and whole-brain monitoring. Their utility is demonstrated in studies of the mesolimbic reward pathway by simultaneously interfacing with the ventral tegmental area and nucleus accumbens in mice and characterizing the neurophysiological effects of a stimulant drug. This study highlights the potential of these fibers to probe electrical, optical, and chemical signaling across multiple brain regions in both mechanistic and translational studies.

neuroscience↗

bioRxiv2021

Customizing Multifunctional Neural Interfaces through Thermal Drawing Process

Fiber drawing enables scalable fabrication of multifunctional flexible fibers that integrate electrical, optical and microfluidic modalities to record and modulate neural activity. Constraints on thermomechanical properties of materials, however, have prevented integrated drawing of metal electrodes with low-loss polymer waveguides for concurrent electrical recording and optical neuromodulation. Here we introduce two fabrication approaches: (1) an iterative thermal drawing with a soft, low melting temperature (Tm) metal indium, and (2) a metal convergence drawing with traditionally non-drawable high Tm metal tungsten. Both approaches deliver multifunctional flexible neural interfaces with low-impedance metallic electrodes and low-loss waveguides, capable of recording optically-evoked and spontaneous neural activity in mice over several weeks. We couple these fibers with a light-weight mechanical microdrive (1g) that enables depth-specific interrogation of neural circuits in mice following chronic implantation. Finally, we demonstrate the compatibility of these fibers with magnetic resonance imaging (MRI) and apply them to visualize the delivery of chemical payloads through the integrated channels in real time. Together, these advances expand the domains of application of the fiber-based neural probes in neuroscience and neuroengineering.

neuroscience↗

bioRxiv2021

Hemodynamic molecular imaging of tumor-associated enzyme activity in the living brain.

Molecular imaging could have great utility for detecting, classifying, and guiding treatment of brain disorders, but existing probes offer limited capability for assessing relevant physiological parameters. Here we describe a potent approach for noninvasive mapping of cancer-associated enzyme activity using a molecular sensor that acts on the vasculature, providing a diagnostic readout via local changes in hemodynamic image contrast. The sensor is targeted at the fibroblast activation protein (FAP), an extracellular dipeptidase and clinically relevant biomarker of brain tumor biology. Optimal FAP sensor variants were identified by screening a series of prototypes for responsiveness in a cell-based bioassay. The best variant was then applied for quantitative neuroimaging of FAP activity in rats, where it reveals nanomolar-scale FAP expression by xeno-grafted tumor cells. The activated probe also induces robust hemodynamic contrast in nonhuman primate brain. This work thus demonstrates a translatable strategy for ultrasensitive functional imaging of molecular targets in neuromedicine.

bioengineering↗

bioRxiv2019

Target-responsive vasoactive probes for ultrasensitive molecular imaging

The ability to monitor molecules volumetrically throughout the body could provide valuable biomarkers for studies of healthy function and disease, but noninvasive detection of molecular targets in living subjects often suffers from poor sensitivity or selectivity. Here we describe a family of potent imaging probes that can be activated by molecules of interest in deep tissue, providing a basis for mapping nanomolar-scale analytes without the radiation or heavy metal content associated with traditional molecular imaging agents. The probes are reversibly-caged vasodilators that induce responses detectable by hemodynamic imaging; they are constructed by combining vasoactive peptides with synthetic chemical appendages and protein blocking domains. We use this architecture to create ultrasensitive biotin-responsive imaging agents, which we apply for wide-field mapping of targets in rat brains using functional magnetic resonance imaging. We also adapt the sensor design for detecting the neurotransmitter dopamine, illustrating versatility of this approach for addressing biologically important molecules.

bioengineering↗

bioRxiv2017

Eukaryotically expressed encapsulins as orthogonal compartments for multiscale molecular imaging

We have genetically controlled compartmentalization in eukaryotic cells by heterologous expression of bacterial encapsulin shell and cargo proteins to engineer enclosed enzymatic reactions and size-controlled metal biomineralization. The orthogonal shell protein (EncA) from M. xanthus efficiently auto-assembled inside mammalian cells into nanocompartments to which sets of native (EncB,C,D) and engineered cargo proteins self-targeted. This enabled localized bimolecular fluorescence and enzyme complementation with selective access to substrates via the pores in the nanoshell. Encapsulation of the enzyme tyrosinase lead to the confinement of toxic melanin production for robust detection via multispectral optoacoustic tomography (MSOT). Co-expression of ferritin-like native cargo (EncB or EncC) resulted in efficient iron sequestration that produced substantial contrast by magnetic resonance imaging (MRI) and enabled magnetic cell sorting. The monodisperse, spherical, and iron-loading nanoshells also proved to be excellent genetically encoded markers for cryo-electron tomography (cryo-ET). In general, eukaryotically expressed encapsulins enable cellular engineering of spatially confined multicomponent processes with versatile applications in multiscale molecular imaging, as well as intriguing implications for metabolic engineering and cellular therapy.

synthetic biology↗