Puzzled by the observation that rats could find shortcuts when navigating a maze, in 1948 Edward Tolman proposed that animals are able to create an internal representation of the environments they move in, and use this representation to implement sophisticated goal-directed behaviors, like finding shortcuts. He called this representation a “cognitive map” and speculated that such a map could be efficiently used for other psychological functions, such as decision making, learning, memory, reasoning, and imagination.In the 70 years that followed, neural correlates of the cognitive map were found in the entorhinal cortex and hippocampus of the mammalian brain, instantiated in single neurons whose activity is tuned to specific variables associated with space, like the animal’s location (place and grid cells), orientation (head-direction cells), or proximity to boundaries (border cells).The cognitive map is not hard-wired into an animal’s brain: infant animals are equipped with only a rudimentary representation of space, whose structural and functional correlates develop over an extended period of time after birth. During this time, spatially-tuned activity patterns like those of place and grid cells emerge and increase their stability and precision, while the animal progressively deploys more sophisticated navigational strategies to reach its goals. The mechanisms by which a developing brain acquires the ability to create an internal representation of space remain to be elucidated. How do you build a cognitive map during development? To answer this question, I propose to use a systems-neuroscience approach to study the development of the entorhinal-hippocampal network, in order to dissect the contribution of specific subpopulations of neurons to the assembly and function of the cognitive map.In my previous work, I discovered that an activity-dependent signal relayed by entorhinal stellate cells drives the step-wise maturation of the entorhinal-hippocampal network. Moreover, I revealed that entorhinal activity is temporally organized in stereotyped motifs like ensembles and sequences as would be expected in an “attractor network”, which might support the firing of grid and place cells. Here, I will build on this knowledge to answer three main questions: (1) What is the origin of the signals that drive the maturation of the entorhinal-hippocampal network? (2) Why is entorhinal activity temporally organized into stereotyped motifs like ensembles and sequences, and when and how do these motifs emerge during development? (3) What is the impact of early-life experience on the function of the cognitive map? My hypothesis are that (1) the instructive signals for the maturation of the entorhinal-hippocampal network originate cell-autonomously in stellate cells, and their propagation is modulated by the animal´s locomotion early during development; (2) the interplay between stellate cells and the hippocampus drives the progressive emergence of an attractor network in the medial entorhinal cortex, for the production of temporally organized activity motifs; (3) the integration of sensory and motor experience early during development drives the emergence and refinement of the cognitive map.To test these hypotheses, we will deploy cutting-edge technologies to study the structure and function of developing neuronal circuits. We will implement a viral strategy to visualize neurons with monosynaptic connections to stellate cells, and optogenetic and chemogenetic approaches to test the involvement of these neurons in the maturation of the entorhinal-hippocampal network. We will make use of 2-photon calcium imaging to simultaneously record the activity of hundreds of entorhinal neurons over consecutive developmental stages in behaving pups, and use dimensionality-reduction techniques to visualize stereotyped activity motifs in their population activity. We will use chronically-implanted electrodes to identify spatially-tuned activity patterns in the entorhinal cortex and hippocampus, and characterize their properties when animals are raised in sensory-poor conditions.The knowledge gathered with my projects will represent a breakthrough in our understanding of the development and function of the cognitive map, and it will provide unprecedented insight into the mechanisms driving the functional maturation of circuits located in high-end areas of cortex, where cognitive functions arise. But this proposal has the potential to go beyond basic research. Since psychological traumas and genetic dysfunctions targeting the development of higher-cognitive areas have been implicated in disorders like autism, depression, or intellectual disabilities, the experiments of this proposal will lay the foundation for a larger research vision aimed at identifying and correcting pathological deviations that have their origin in neurodevelopmental disorders.