We aim at deciphering the role of Vangl2, a main component of the planar cell polarity (PCP) signaling, in hippocampal network function which is to compute information involving object location, spatial contexts and events relevant for every day memory function. PCP signaling is necessary for proper coordination of development and growth of many tissues, by controlling notably intercellular and intracellular communication, and integrating signaling cues leading to a reorganization of the cytoskeleton. In the brain, growing evidence suggests that PCP signaling is fundamental for neuronal development, including neuronal migration, neuronal polarity and maturation, axonal guidance, but also dendrite morphogenesis, synaptogenesis and synaptic plasticity. But a fundamental and yet unresolved question is why PCP proteins are also expressed at the adult stage in the hippocampus and neuronal circuits critical for cognition and memory. Recent work from our lab (Montcouquiol/Sans) revealed specific behavioral consequences of brain-specific disruptions of the PCP-signaling scrib gene, using mainly deletion or mutation models in mice (Moreau et al, J. Neurosci. 2010; Hilal et al, Cerebral Cortex, 2017; Ezan et al., in preparation). Preliminary results from our lab suggest that early or late deletion of vangl2, restricted to the brain, lead to altered hippocampus-dependent memory functions (Moreau et al., in preparation; Robert et al., SFN 2016 poster #356.09; in preparation). This suggests that unexpectedly, PCP proteins may be essential component of the adult central nervous system and required for proper function of memory-related brain structures such as the hippocampus. Our project is to combine molecular, behavioral and electrophysiological approaches to assess hippocampal function in the adult mouse after manipulating the expression of Vangl2 in specific hippocampal neuronal populations. Here, we will use well-established and new molecular, cellular and genetic tools to manipulate PCP signaling (Montcouquiol-Sans lab), combined with in vivo recording associated with behavioral paradigms (Leinekugel lab) to evaluate the consequences in terms of cellular communication and circuit function. A strong innovative aspect of this proposal is to develop new AAV or lentivirus construction driving the cre-recombinase or other specific activating genes or dominant negative constructs into specific neuronal population. Using these tools, it will be possible to achieve spatial and temporal activation or inhibition of the vangl2-dependent pathway in adult mice. Combined with high-end electrophysiological recordings and opto- and pharmaco-genetic manipulation of the activity of hilar mossy cells, we will also have the very timely opportunity to address the respective roles of dentate mossy and granule cells in hippocampal circuit function. This project will provide novel conceptual insights into the role of Vangl2-dependent signaling and function in the hippocampal circuit, and more generally pave the way for a better understanding of the importance of PCPs in adult neuronal microcircuits.