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Abstract: Research in quantum computing has offered many new physical insights and a potential to exponentially increase the computational power that can be harnessed to solve important problems in science and technology. The largest fundamental barrier to building a scalable quantum computer is errors caused by decoherence. Topological quantum computing overcomes this barrier by exploiting topological materials which, by their nature, limit errors. In this colloquium, I will discuss how to engineer topological superconductors supporting Majorana zero-energy modes at the interface of a conventional superconductor and a semiconductor with spin-orbit interaction. I will present recent results by the Microsoft Quantum team consistent with the emergence of topological superconductivity in proximitized semiconductor nanowires. Finally, I will present a proposal for scalable quantum computing involving topological qubits which comprise of superconducting islands in a Coulomb blockade regime hosting aggregates of four or more Majorana zero modes.

Dahlia Kushinsky- Daily normalization of E/I-ratio by light-driven transcription maintains visual processing

Abstract: Consistent and reliable encoding of sensory information is essential for an animal’s survival. However, sensory input in an animal’s environment is constantly changing, likely resulting in changes in the brain at the level of molecules, synapses, and cellular circuitry. It is therefore unclear which elements of the system are stable or dynamic, and what mechanisms allow for overall stability of the brain throughout an animal’s life. To address this question, we focused on the visual cortex of adult mice and took advantage of the daily sensory transitions from the dark of night to daylight and back to darkness during a single day. By using RNA-seq, patch clamp slice electrophysiology, and in vivo longitudinal calcium imaging in awake mice, we monitor the light driven changes in molecules, synapses, and cells across a single day. At each of these levels (molecular, synaptic, and cellular), we find rapid sensory-driven increases shortly after transition from darkness to light which is then normalized later in the day. Based on these findings, we suggest that sensory-driven genetic changes maintain functional stability of neural circuits by regulating E/I ratio in excitatory neurons every day.

Michael Sokoletsy-
Isolated correlates of perception in the posterior cortex

Abstract: To uncover the neural mechanisms of stimulus perception, experimenters commonly use tasks in which subjects are repeatedly presented with a weak stimulus and instructed to report, via movement, if they perceived the stimulus. The difference in neural activity between reported stimulus (hit) and unreported stimulus (miss) trials is then seen as potentially perception-related. However, recent studies found that activity related to the report spreads throughout the brain, calling into question to what extent such tasks may be conflating activity that is perception-related with activity that is report-related. To isolate perception-related activity, we developed a paradigm in which the same mice were trained to report either the presence or absence of a whisker stimulus. We found that isolated perception-related activity appeared within a posterio-parietal network of cortical regions contralateral to the stimulus, was on average an order of magnitude lower than the hit versus miss difference, and began just after the low-level stimulus response. In addition, we performed controls to check that it is specifically associated with performance and is not the result of differences in time or uninstructed movements across the tasks. In summary, we revealed for the first time in mice the cortical areas that are associated specifically with the perception of a sensory stimulus and independently of the report.

Advanced methods now allow fast, cellular-level recording of neural activity across the mammalian brain, enabling exploration of how brain-wide dynamical patterns might give rise to complex behavioral states, such as the clinically important state of dissociation. We established a dissociation-like state in mice, induced by administration of ketamine or phencyclidine. Large-scale neural recording revealed that these dissociative agents elicited a 1–3-Hz rhythm in layer 5 neurons of retrosplenial cortex, uncoupled from most other brain regions except thalamus. Additionally, using brain-wide intracranial electrical recording in a patient with focal epilepsy, the human experience of dissociation was linked to a similar ~3 Hz rhythm in posteromedial cortex (homologous to mouse retrosplenial cortex), and stimulation of this area induced dissociation. 
 

Rats (if trained appropriately) can apply to some set of tactile stimuli a multitude of different perceptual and memory capacities. For instance, they can express working memory, where the most recent stimulus has to be stored and retrieved to support a comparison to the ongoing stimulus. They can express reference memory, where the ongoing stimulus has to be compared to some stable, internal boundary. They can change that internal boundary as a function of stimulus statistics. They can learn to ignore stimuli of the same sensory modality, if untagged by an acoustic cue. While it might seem easiest to draw up computational/functional frameworks tailor-made to each behavior, we are trying to explain several different behaviors by common algorithms. This informal discussion will mainly present ongoing psychophysical studies, with a few preliminary physiological added here and there.
 

Luminescent materials with their rich color palettes have revolutionized both science and technology through the ability to distinguish between spectrally resolved colors for a wide range of applications from sensing to molecular steganography through high-end electronics and biomedical imaging. Yet, light-based colors suffer from limitations, such as strong scattering and absorbance in opaque media, restricted spectral resolution, photo-bleaching, intolerance for color-palette extendibility and more. Amongst the diverse capabilities and many advantages of Nuclear Magnetic Resonance (spectroscopy and imaging) several are unique, e.g., the sensitivity of the chemical shifts to the chemical environment, the penetrateability of MR signals across opaque objects and the ability to produce three dimensional images of studied subjects. Here, I discuss our recent developments of molecular probes that are capable to generate artificial MR-based colors. To this end, we use synthetic chemistry, nanofabrication, and protein engineering approaches to generate novel molecular formulations (small molecules, nanocrystals (NCs), supramolecular assemblies and proteins) as MRI sensors with unique, advantageous properties (sensitivity, specificity, orthogonality, etc.). I will also discuss how the very same molecular probes can be used to better understand fundamental scientific questions in supramolecular chemistry (e.g., kinetic features of dynamically exchanging molecular systems) and materials science (e.g., understanding and controlling NCs’ formation pathways).

SARM1 is a central executor of neurodegeneration. Remarkably, neurons from SARM1 knock-out mice (which appear to be normal in many respects) show prolonged resistance for neuronal degeneration after mechanical damage, oxidative stress, and chemotherapy treatments. Mechanistically, SARM1 contains NADase activity, which, in response to nerve injury, depletes the key cellular metabolite, NAD+. To gain structural knowledge of SARM1 we use X-ray crystallography of isolated SARM1 domains and single particle EM 3D reconstruction of the intact protein. We discovered that SARM1, like other apoptotic complexes, assembles into an oligomeric ring. Structure analysis and additional experiments in cultured cells points at a surprising molecular mechanism by which SARM1 is kept inactive during homeostasis and how it becomes activated in response to metabolic and oxidative stress conditions 1,2,3.

1 Sporny, M. et al. Structural Evidence for an Octameric Ring Arrangement of SARM1. J Mol Biol
431, 3591-3605, doi:10.1016/j.jmb.2019.06.030 (2019).

2 Sporny, M. et al. Structural basis for SARM1 inhibition and activation under energetic stress. Elife 9, doi:10.7554/eLife.62021 (2020).

3.Khazma T. et al. A Duplex Structure of SARM1 Octamers Induced by a New Inhibitor. bioRxiv doi.org/10.1101/2022.03.02.482641 (2022).

Self-assembly and self-organization are two big challenges in the natural sciences. What are the rules governing the emergence of greater structures from unassuming elements? Does statistical-mechanics restrict their complexity? Biochemical processes can shape highly specific structures and function on the macro-scale using only molecular information. Although stereochemistry has been a central focus of molecular sciences since Pasteur, its synthetic province has been restricted to the nanometric scale. In my talk, I will describe how to propagate molecular information to self-assemble free-form architectures on the micron-scale and beyond. These architectures are a thousand times greater than their constituent molecules yet have a preprogrammed geometry and chirality. I will then show how to animate such synthetic microstructures into bacteria-like micro-swimmers. Previous artificial microswimmers relied on an external chemical fuel to drive their propulsion which restricted their operational concentration as they competed locally over fuel. I will demonstrate how to use material science and physical chemistry to self-assemble fuel-free micro-swimmers that are driven solely by light. The fuel independence allows the swimmers to stay active even at high densities, where they form turbulent flow structures (previously seen in living fluids), and cooperate to perform a greater task.