CTBP1 SHAPES CELL-TO-CELL COMMUNICATION AT THE NEURON-GLIA INTERFACE IN THE ADULT BRAIN

CTBP1 is a dual-function protein expressed throughout the body, acting as both a nuclear transcriptional co-repressor and a cytosolic regulator of membrane trafficking. Rare de novo mutations in CTBP1 can lead to a condition known as hypotonia, ataxia, developmental delay and tooth enamel syndrome (HADDTS). This condition is characterised by neurological and neurodevelopmental deficits, which indicates the important role of CTBP1 in the nervous system. To date, the function of CTBP1 has primarily been studied in neuronal cells. In neurons, CTBP1 regulates synaptogenesis and the efficiency of neurotransmission by controlling the expression of activity-regulated genes. Additionally, CTBP1 controls the activity of lipid-modifying enzymes in presynaptic terminals, which are required for the efficient retrieval of synaptic vesicles. Our recent data showed that CTBP1 is also abundant in glial cells in the adult brain, including astrocytes, oligodendrocytes and microglia. Furthermore, deleting CTBP1 specifically in glial cells affected the structural and functional properties of neocortical circuits in the adult brain. In this study, we examined the specific functions of CTBP1 in neuronal and non-neuronal cells by using cell-type-specific deletion in mice and primary cultures. Our focus was on neurotransmission, cell-type-specific expression, and metabolic regulation. Together, these results indicate that glial CTBP1 contributes to the structural and functional maintenance of neocortical circuits in the adult brain by shaping electrochemical and metabolic communication at the neuron–glia interface.