Brain information processing is commonly thought to be a neuronal performance. However recent data point to a key role of astrocytes in brain development, activity and pathology. Indeed astrocytes are now viewed as crucial elements of the brain circuitry that control synapse formation, maturation, activity and elimination. How do astrocytes exert such control is matter of intense research, as they are now known to participate in critical developmental periods as well as in psychiatric disorders involving synapse alterations. Thus unraveling how astrocytes control synaptic circuit formation and maturation is crucial, not only for our understanding of brain development, but also for identifying novel therapeutic targets. We recently found that connexin 30 (Cx30), an astroglial gap junction subunit expressed postnatally, tunes synaptic activity via an unprecedented non-channel function setting the proximity of glial processes to synaptic clefts, essential for synaptic glutamate clearance efficacy. Our work not only reveals Cx30 as a key determinant of glial synapse coverage, but also extends the classical model of neuroglial interactions in which astrocytes are generally considered as extrasynaptic elements indirectly regulating neurotransmission. Yet the molecular mechanisms involved in such control, its dynamic regulation by activity and impact in a native developmental context are unknown. We will now address these important questions, focusing on the involvement of this novel astroglial function in wiring developing synaptic circuits. Thus using a multidisciplinary approach we will investigate: 1) the molecular and cellular mechanisms underlying Cx30 regulation of synaptic function 2) the activity-dependent dynamics of Cx30 function at synapses 3) a role for Cx30 in wiring synaptic circuits during critical developmental periods This ambitious project will provide essential knowledge on the molecular mechanisms underlying astroglial control of synaptic circuits.

This project is about the representation of particular objects in language and thought, a topic which has been at the forefront of philosophical attention for more than a century. About fifty years ago, ‘descriptivism’ was demoted from its dominant position in philosophy in favour of the theory of ‘direct reference’. A similar shift away from descriptivism has been a noticeable feature of work on the representation of objects in cognitive science, where the notion of an ‘object file’ has made it possible to unify research on perception and on infant cognition. The object file construct is in many respects similar to the philosophical idea of direct (non-descriptive) grounding for thoughts about particulars, and this has given rise to a new research program: the generalization of the file idea from perception to thought. Thus the last decade has seen the development of the mental file framework, according to which nondescriptive thoughts about particulars (so-called ‘singular thoughts’), whether or not they are based on perception, involve mental files whose 'reference' does not depend on category information to be found in the file but on certain relations to the object the obtaining of which triggers the opening of the file. The mental file framework has attracted considerable attention not only in philosophy, but also in psychology (Perner) and linguistics (Kamp). It has also inspired work in aesthetics and the philosophy of fiction. Successful though it is, the mental file framework currently faces what may be described as a foundational crisis. According to a recurrent piece of criticism, it fails to provide appropriate identity and persistence conditions for mental files. This threatens the credibility of the framework, reduced to a convenient metaphor, and puts it at risk despite its high promises and considerable appeal. The aim of this philosophical project is to end the crisis by entirely rethinking the foundations of the framework.

Redox chemistry provides the fundamental basis for numerous energy-related electrochemical devices, among which Li-ion batteries (LIB) have become the premier energy storage technology for portable electronics and vehicle electrification. Throughout its history, LIB technology has relied on cationic redox reactions as the sole source of energy storage capacity. This is no longer true. In 2013 we demonstrated that Li-driven reversible formation of (O2)n peroxo-groups in new layered oxides led to extraordinary increases in energy storage capacity. This finding, which is receiving worldwide attention, represents a transformational approach for creating advanced energy materials for not only energy storage, but also water splitting applications as both involve peroxo species. However, as is often the case with new discoveries, the fundamental science at work needs to be rationalized and understood. Specifically, what are the mechanisms for ion and electron transport in these Li-driven anionic redox reactions? To address these seminal questions and to widen the spectrum of materials (transition metal and anion) showing anionic redox chemistry, we propose a comprehensive research program that combines experimental and computational methods. The experimental methods include structural and electrochemical analyses (both ex-situ and in-situ), and computational modeling will be based on first-principles DFT for identifying the fundamental processes that enable anionic redox activity. The knowledge gained from these studies, in combination with our expertise in inorganic synthesis, will enable us to design a new generation of Li-ion battery materials that exhibit substantial increases (20 -30%) in energy storage capacity, with additional impacts on the development of Na-ion batteries and the design of water splitting catalysts, with the feasibility to surpass current water splitting efficiencies via novel (O2)n-based electrocatalysts.