Local circuit architecture facilitates the emergence of feature selectivity in the cerebral cortex 1 . In the hippocampus, it remains unknown whether local computations supported by specific connectivity motifs 2 regulate the spatial receptive fields of pyramidal cells 3 . Here, we developed an in vivo electroporation method for monosynaptic retrograde tracing 4 and optogenetics manipulation at single-cell resolution to interrogate the dynamic interaction of place cells with their microcircuitry during navigation. We found a previously unrecognized local circuit mechanism in CA1 whereby the spatial tuning of an individual place cell can propagate to a functionally recurrent subnetwork 5 to which it belongs. The emergence of place fields in individual neurons led to the development of inverse selectivity in a subset of their presynaptic interneurons, and recruited functionally coupled place cells at that location. Thus, the spatial selectivity of single CA1 neurons is amplified through local circuit plasticity to enable effective multi-neuronal representations that can flexibly scale environmental features locally without degrading the feedforward input structure.

The developmental transition between axon guidance and synapse formation is critical for circuit assembly but still poorly understood at the molecular level. We hypothesized that this key transition could be regulated by axon guidance cues switching their function to regulate synaptogenesis with subcellular specificity. Here, we report evidence for such a functional switch, describing a novel role for the axon guidance molecule Robo2 in excitatory synapse formation onto dendrites of CA1 pyramidal neurons (PNs) in the mouse hippocampus. Cell-autonomous deletion of Robo2 from CA1 PNs leads to a drastic reduction of the number of excitatory synapses specifically in proximal dendritic compartments. At the molecular level, we show that this novel postsynaptic function of Robo2 depends on both its canonical ligand Slit and a novel interaction with presynaptic Neurexins. Biophysical analysis reveals that Robo2 binds directly to Neurexins via itsIg4-5 domains. In vivo 2-photon Ca 2+ imaging of CA1 PNs during spatial navigation in mice shows that sparse deletion of Robo2 during development drastically reduces the likelihood of place cell emergence and alters spatial coding properties of the remaining place cells. Our results identify Robo2 as a novel molecular effector linking synaptic specificity to the acquisition of spatial coding properties characterizing hippocampal circuits.Proper circuit function relies on the establishment of synaptic connections characterized by a high degree of cell type and subcellular specificity. How this striking degree of synaptic specificity is achieved during development remains poorly understood, especially in the complex brains of mammals. Many cell surface molecules that mediate molecular recognition between axons and dendrites during circuit development have been identified 1-4 . These trans-synaptic adhesion molecules are often expressed in a cell-type specific manner 5 thereby determining the pool of a cell's possible synaptic partners. Some classes of these molecules have synaptic organizing properties evidenced by their direct or indirect ability to recruit key pre-and postsynaptic proteins. When axons reach their target areas, a cellular switch from a phase of growth and branching to synaptogenesis is observed. This switch is characterized by dynamic instability of adhesion progressively leading to more stable patterns of synaptic connectivity characterizing adult circuits. One of the foremost outstanding questions in neuroscience is how synapse formation is mechanistically integrated with earlier developmental steps such as axon guidance 3 and branching. One potential mechanism for coordinating this transition relies on the possibility that axon guidance cues acquire synaptogenic functions during circuit wiring. Indeed, evidence for such dual use of developmental molecules has been reported 6 . However, it remains unclear what prompts molecules to switch their function from axon guidance to synaptogenesis.Here we report that the well-studied axon guidance ligand-receptor pair Sl...

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