The COLORI proposal is devoted to the theoretical description, the numerical modeling, and the experimental study of cold and ultracold molecular collisions driven by long-range forces in the presence of strongly confining external potentials. The project brings together one theoretical and one experimental team. The coordinator IPR-Rennes has a strong theoretical background in the molecular dynamics field, the LENS-Florence partner is internationally recognized for its experimental contribution to the study of atomic and molecular gases in the ultracold domain. Experimental groups worldwide have developed the capability to cool and manipulate a large variety of atomic, molecular, and ionic species, forming the extremely active quantum gases community. Binary collisions occupy a pivotal position in the ultracold gas realm. It suffices to mention that the efficacity of cooling schemes and the quantum phases of an ultracold gas are controlled by two-body elastic and inelastic scattering amplitudes. The quantitative understanding of cold collisions is therefore essential to interpret ongoing experiments on quantum gases. Fortunately, cold collisions can not only be accurately understood, but even accurately controlled. External fields are the tool of choice, capable of influencing the outcome of a collision either by directly modifying the translational motion or by manipulating the internal structure of the colliding partners. Two main research topics can be identified in our proposal. The first one is a joint theoretical and experimental study of confinement effects on collisions of polar KRb bosonic molecules. The experimental developments ongoing at LENS include the set-up of an extremely stable laser system for two-photon transfer of weakly bound molecules to the absolute ground state. This study should allow us to shed light on the long-range interplay between dipolar, electric and optical forces, an extremely interesting topic in view of controlling unwanted reactive chemical processes expected to limit the gas lifetime. Confinement effects will be studied in particular in optical lattices of different dimensionality and crystal symmetry. We expect a wealth of geometric resonance phenomena and lattice-induced scattering events to be accurately described using the numerical tools developed during the project. Novel methodological and computational approaches will have to be proposed to this aim. Inclusion of hyperfine couplings in molecular collisions should allow novel resonance patterns and quantum interference phenomena to be studied. The second part of the COLORI proposal will consider atom-ion collisions in the presence of hyperfine and dynamical ion trap effects. Novel routes to collision control will be investigated by taking into account the interplay of resonances due to internal hyperfine couplings with Landau quantization of motional ion states in a magnetic field. Yet unexplored micromotion effects will be studied in collisions of atoms with ions trapped in Paul traps using both time-independent and time-dependent wavepacket methods. The realization of atom-ion quantum gates and sympathetic cooling of ions by ultracold atoms are only few examples for which a quantitative modeling of collisions is strongly needed. Finally, the numerical codes we propose to develop are expected to set a benchmark for theories based on effective and perturbative approaches to scattering in confined environments. COLORI presents a good equilibrium of scientific tasks between the IPR and LENS partners in the proposal, and between senior and young researchers. Periodic informal meetings are foreseen for coordination purposes. Publications in peer-reviewed journals and presentations in international meetings should help disseminating the main results of the present cooperative project.

Optical microscopy imaging is one of the most powerful approaches for probing the organization of brain tissue at a (sub)cellular level. Several distinct microscopy techniques are available, each with their own advantages and disadvantages in terms of spatial resolution, field-of-view, molecular specificity, and invasiveness of sample preparation. The SMART BRAIN project seeks to advance the complementary measurement of neuronal tissue by different optical imaging technologies, and to develop the in silico integration of images collected by different methods by means of data-driven multimodal image fusion. This process will combine advantages from different source modalities into a single predictive imaging modality. Specifically, we will integrate 3-D multiphoton microscopy (MPM) data with 3-D light-sheet microscopy (LSM) measurements, to deliver a single ‘fused’ predictive imaging modality that combines the molecular specificity of LSM with the non-invasive sample preparation of MPM. The fused modality will deliver LSM-grade information while avoiding LSM’s invasive clearing procedure, in case tissue needs to be safeguarded for other analyses or for broad LSM-based molecular targeting post-MPM. Furthermore, we will explore fusion of MPM with super-resolution microscopy (STED), to predict 2-D multiphoton tissue observations at up to 10 times the diffraction limit. This project’s unique multidisciplinary approach has the potential to provide an organizational description of brain tissue that surpasses what any single imaging technique can provide. The proposed approach is based on advanced machine learning algorithms originally developed for integration between 2-D imaging mass spectrometry and standard 2-D stained microscopy, with proof-of-concepts demonstrated in murine brain tissue. The SMART BRAIN project will extend these methods for fusion of multiphoton, light-sheet, and STED microscopy. The goal is to discover relationships between observations in the different modalities, to mathematically model them, and then to use them for prediction of morphological information at spatial resolutions beyond instrumental limitations or in tissue areas where not all data types are measured. Fusion of different datasets will be initiated on murine brain tissue, and subsequently extended to human brain samples. Specimens, provided by the neurosurgery partners in the consortium will be obtained from patients showing temporal lobe epilepsy and block of hippocampus and amygdala, as well as from autopsy of healthy subjects, yielding precious information on human brain morphology. The SMART BRAIN project will (i) provide a new multi-modal approach exceeding the state of the art in single-modality optical microscopy, (ii) support the HBP consortium with a previously unavailable fused data type and with unprecedented information on human brain morphology, and (iii) provide a novel methodology for combination with clinical imaging for advanced diagnostics.

Memory determines the uniqueness of our personal history, and is decisive for each individual to survive and prosper. It is a multistate process that includes consolidation and retrieval. Impairment of memory processing may result in intrusive ideation, triggering maladaptive responses that are key symptoms of psychiatric disorders such as generalized anxiety, obsessive-compulsive disorders, post-traumatic stress disorder and phobias. Insights leading to better treatments of these diseases can be gained by understanding the neurobiology of emotional memory. Several neurotransmitters contribute to memory formation and in particular, the integrity of the hypothalamic histamine (HA) system is necessary for the different phases of emotional memory formation and retrieval. HA neurons are organized into functionally distinct circuits, display selective control mechanisms and impinge on different brain regions involved in memory, including amygdala, prefrontal cortex and hippocampus. HA neurotransmission is critical to provide the brain with the plasticity necessary to store and retrieve memories through recruitment of alternative circuits. Despite the extensive literature reporting the importance of brain HA in learning and memory, a detailed map of HA pathways that are activated at different time points during memory formation and retrieval is currently not available. HA-CTion aims at elucidating how brain HA networks and selected ligands of HA receptors modulate emotional memory formation. The project poses particular emphasis on H1 receptor (H1R) ligands, as antagonists of this receptor are among the most used drugs worldwide, and on new H3R compounds. These ligands have memory impairing or memory enhancing effects that could be exploited to modulate emotional memory processing. In this respect, animals are crucial to bridge the translational gap between preclinical and clinical research, as the basic architecture of emotional memory and its mechanisms are conserved across species. HA-CTion will use a validated preclinical model, the inhibitory avoidance test, to establish a strong emotional memory in mice. HA-CTion will analyse the architecture and function of circuits that link hypothalamic HA neurons to its target neurons (e.g., in the cortex, hippocampus or amygdala) implicated in the processing of emotional memory consolidation and retrieval. The proposal is built on close cooperative actions of 4 partners from 3 EU countries. The combined use of new neuroanatomical, chemogenetic and photo-pharmacological tools will uncover previously unidentified HA brain circuitries and mechanisms involved in emotional memory consolidation and retrieval with unprecedented temporal and spatial resolution. HA-Ction will provide experimentally testable hypotheses to guide future research in humans, offering possible targets for a novel pharmacotherapy to treat dysfunctional aversive memories and increase the efficacy of exposure psychotherapies.