Past events

Brain is often viewed as large neuronal connectome where the information is encoded in the patterns of action potentials and stored in the changes of synaptic strength or appearance of new wiring routes. However, recent studies have demonstrated that astrocytes also possess complex patterns of calcium signals influenced by neuronal activity. Astrocytic calcium signals regulate various functions of these cells including release of gliotransmitters and morphological changes in the astrocytic processes (Tanaka et al., 2013). It has been tempting to suggest that information in astrocytes is encoded in the frequency of calcium events, similar to patters of neuronal action potentials. Synaptically released neurotransmitters thought to trigger new calcium events in perisynaptic astrocytic processes (PAPs) though activation of metabotropic glutamate receptors (mGluRs). In contrast, our recent findings suggest that PAPs are devoid of calcium stores that are required for mGluR-mediated calcium signaling (Patrushev et al., 2013). This makes unlikely any significant role of mGluRs in triggering calcium events in PAPs. Instead, we show that activation of ‘extrasynaptic’ astrocytic mGluRs increases proportion of spatially extended calcium events in the power-law based distribution of calcium event sizes (Wu et al., 2014). This effect takes place without any significant increase in the frequency of calcium events. These findings suggest that astrocytic response to surrounding neuronal activity is rather encoded in spatial characteristics of their calcium events and fundamentally different from temporal information coding in neurons (e.g. coincidence detection, action potentials sequences etc). Nevertheless, we cannot exclude local ionic changes in PAPs in response to synaptic activity. For example, potassium ions accumulate in the synaptic cleft of glutamatergic synapses during repetitive activity. We have demonstrated that the bulk of these ions is contributed by potassium efflux through postsynaptic NMDA receptors (Shih et al., 2013). Potassium mediated depolarization of presynaptic terminal increases glutamate release probability. Now we have found that accumulation of intracleft potassium during repetitive synaptic activity could also inhibit astrocytic glutamate uptake by depolarizing PAPs. This extends glutamate dwell-time in the synaptic cleft and boosts glutamate spillover effects.

Homeostatic synaptic scaling is thought to occur cell-wide, but recent evidence suggests this form of stabilizing plasticity can be implemented more locally in reduced preparations. To investigate the spatial scales of plasticity in vivo, we used repeated two-photon imaging in mouse visual cortex after sensory deprivation to measure TNF-α dependent increases in spine size as a proxy for synaptic scaling in vivo in both excitatory and inhibitory neurons. We found that after sensory deprivation, increases in spine size are restricted to a subset of dendritic branches, which we confirmed using immunohistochemistry. We found that the dendritic branches that had individual spines that increased in size following deprivation, also underwent a decrease in spine density. Within a given dendritic branch, the degree of spine size increases is proportional to recent spine loss within that branch. Using computational simulations, we show that this compartmentalized form of synaptic scaling better retained the previously established input-output relationship in the cell, while restoring activity levels. We then investigated the relationship between new spines that form after this spine loss and strengthening and find that their spatial positioning facilitates strengthening of maintained synapses.

Some animals, especially those living under water use mirrors rather than lenses to form images. Two general strategies exist in nature for forming images using mirrors, exemplified by the concave mirrored eyes of the scallop1 and the reflecting compound eyes of crustaceans2. Here we discuss these two remarkable visual systems and show how the whole hierarchical organization of the mirrors are exquisitely controlled for image-formation from the structure and morphology of the substituent reflecting crystals at the nanoscale to the overall shape of the mirrors at the millimeter scale. Based on our understanding of the optics and structure we can predict what the animal should be seeing. Whether the neural system can integrate all this information, has yet to be determined. From a materials science perspective, understanding how organisms exert such extraord! inary control over the formation and organization of organic crystals provides inspiration for the development of new organic crystalline materials with rationally designed morphologies and properties. 1B.A. Palmer*, G.J. Taylor, V. Brumfeld, D. Gur, M. Shemesh, N. Elad, A. Osherov, D. Oron, S. Weiner, L. Addadi, Science 2017, 358, 1172. 2B.A. Palmer*, A. Hirsch, V. Brumfeld, N. Elad, D. Oron, L. Kronik, L. Leiserowitz, S. Weiner, L. Addadi,* PNAS, 2018, 115, 2299.

Current state of the art ultra-high field MRI scanners have already achieved submillimeter resolution in 3D imaging of the human brain. Studies of the functional activity in the brain - by Blood Oxygen Level Dependent (BOLD) technique - have utilized this capability to observe mesoscopic (200-300µm) structures in humans. However, does BOLD tell us the full story? With current state of the art in mind, we are looking for the next step forward to better understand the brain physiology. I will share an on-going research on the mapping of electrical properties, aimed at studying functional activity in the human brain and offering a more direct probe of neuronal activity. The research includes a new computational technique for estimating electrical properties from an MR experiment, as well as the implementation of fast acquisition techniques. I will also show a correlation between changes in the electrical conductivity and basic activation paradigms (visual or motor) demonstrating faster response versus BOLD signal.