Synaptic communication mediates the assembly of a self-organizing circuit that controls reproduction

Migration of GnRH neurons, a critical step for vertebrate reproduction, depends on circuit-intrinsic synaptic communication.
Migration of gonadotropin-releasing hormone (GnRH) neurons from their birthplace in the nasal placode to their hypothalamic destination is critical for vertebrate reproduction and species persistence. While their migration mode as individual GnRH neurons has been extensively studied, the role of GnRH-GnRH cell communication during migration remains largely unexplored. Here, we show in awake zebrafish larvae that migrating GnRH neurons pause at the nasal-forebrain junction and form clusters that act as interhemisphere neuronal ensembles. Within the ensembles, GnRH neurons create an isolated, spontaneously active circuit that is internally wired through monosynaptic glutamatergic synapses into which newborn GnRH neurons integrate before entering the brain. This initial phase of integration drives a phenotypic switch, which is essential for GnRH neurons to properly migrate toward their hypothalamic destination. Together, these experiments reveal a critical step for reproduction, which depends on synaptic communication between migrating GnRH neurons.