Functional recruitment of astrocyte-derived neurons into the mouse visual cortex

Abstract Inducing neurogenesis from glia could permit circuit remodeling and neuron replacement in the brain. Indirect evidence suggests that glia-to-neuron reprogramming is feasible, but the dynamics of conversion have not been directly observed, and it remains unclear whether glia-derived cortical neurons can functionally integrate into brain circuits. Here, we use two-photon imaging to visualize the reprogramming of astroglia into induced neurons in the mouse cortex in vivo. We track the emergence of spontaneous neuron-like calcium transients in astrocyte-derived induced neurons, demonstrating their functional activity in vivo. Importantly, these induced neurons exhibit orientation tuned, visually evoked calcium responses, demonstrating their functional integration into cortical circuitry - a prerequisite for their utility in circuit repair. Thus, astrocytes can be recruited to generate functional neurons in the postnatal cortex, enabling circuit remodeling in perinatal injury or neurodevelopmental disorders without relying on external cellular sources. Competing Interest Statement The authors have declared no competing interest. Data and materials availability All data used in this work are presented in the manuscript, the Supplementary Materials, or can be downloaded from 10.18742/30920522. Plasmids/viruses and other materials generated specifically for use in this work will be provided by BB upon reasonable request. We do not report custom computation, models or simulations that go beyond common routines or analysis as described in the text or cited but code used for analysis is available on request to the lead contact(s).