לוח שנה משולב

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.

Decision-making requires a consideration of both costs and benefits. Although mesolimbic dopamine (DA) plays an established role in reward-related decisions, there has been longstanding controversy over its sensitivity to costs vs benefits. Manipulations of DA function imply a primary role in mediating cost calculations, while DA recordings suggest a preference for encoding benefit. These studies often confound cost and benefit by varying both simultaneously, and rarely combine correlational and causal tools to explore how encoding relates to behavior. Here we independently varied costs and benefits, studying DA's role using both recording and manipulation. We found that DA release reflects changes in both cost and benefit, although the precise relationship depended on the time within a trial and the site of DA release. Then we used behavioral economics to probe how these patterns of DA release relate to two important behavioral parameters: a mouse's preferred level of reward consumption and the amount of work it is willing to expend to maintain that consumption. We found that DA release in the nucleus accumbens core and dorsolateral striatum does not predict an animal's preferred level of consumption. It does, however, strongly reflect an animal's willingness to work for reward. Surprisingly, the more DA released for each reward, the less demand for that reward. The inverse relationship between DA release and demand held true both for natural rewards and optogenetic stimulation of DA release in both striatal targets. Our findings support an inverted-U model of dopamine and reinforcement, where a minimal level of DA release is critical to motivate behavior, but increments above that level actually reduce demand.
Link to join:
https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09

Meeting ID: 954 0689 3197
Password: 750421

While our world is three-dimensional (3D), spatial perception is most often studied in animals and humans navigating across 2D surfaces. I will present two cases in which the consideration of the 3D nature of the world has led us to surprising results. The first case regards the neural recording of mammalian grid cells. Grid cells that are recorded over 2D surfaces create a hexagonal-shaped repetitive lattice, which inspired many theoretical studies to investigate the pattern’s mechanism and function. Upon recording in bats flying through 3D space, we found that grid cells did not exhibit a hexagonal global lattice, but rather showed a local order – with grid-fields exhibiting fixed local distances. Our results in 3D strongly argue against most of the prevailing models of grid-cell function, and we suggest a unified model that explains the results in both 2D and 3D.  The second case regards the perception of 3D space in humans. Different behavioral studies have shown contradicting evidence of human perception of 3D space being either isotropic or vertically compressed. We addressed this question using human experts in 3D motion and navigation – fighter pilots – studied in a flight simulator. We considered two aspects of the perception of 3D space: surrounding space and travelled space. We show that different aspects of the perception of space are shaped differently with experience: whereas the perception of the 3D surrounding space was vertically compressed in both expert and non-expert subjects, fighter pilots exhibited isotropic perception of travelled space, whereas non-expert subjects retained a distorted perception.  Together, our research sheds light on the differences and similarities between the coding of 3D versus 2D space, in both animals and humans.