Astrocytes are highly complex glial cells with numerous fine cellular processes which infiltrate the neuropil to interact with synapses. The mechanisms controlling the establishment of astrocytes’ remarkable morphology and how impairing astrocytic infiltration of the neuropil alters synaptic connectivity are largely unknown. Here we find that cortical astrocyte morphogenesis depends on direct contact with neuronal processes and occurs in tune with the growth and activity of synaptic circuits. Neuroligin (NL) family cell adhesion proteins, NL1, NL2, and NL3, which are expressed by cortical astrocytes, control astrocyte morphogenesis through interactions with neuronal neurexins. Furthermore, in the absence of astrocytic NL2, cortical excitatory synapse formation and function is diminished, whereas inhibitory synaptic function is enhanced. Our findings highlight a novel mechanism of action for NLs and link astrocyte morphogenesis to synaptogenesis. Because NL mutations are implicated in various neurological disorders, these findings also offer an astrocyte-based mechanism of neural pathology.

Leptomeningeal disease has become increasingly prevalent as novel therapeutic interventions extend the survival of cancer patients. Although a majority of leptomeningeal spread occurs secondary to breast cancer, lung cancer, and melanoma, a wide variety of malignancies have been reported as primary sources. Symptoms on presentation are equally diverse, often involving a combination of neurological deficits with the possibility of obstructive hydrocephalus. Diagnosis is definitively made via cerebrospinal fluid cytology for malignant cells, but neuro-imaging with high quality T1-weighted magnetic resonance imaging can aid diagnosis and localization. While leptomeningeal disease is still a terminal, late-stage complication, a variety of treatment modalities, such as intrathecal chemotherapeutics and radiation therapy, have improved median survival from 4–6 weeks to 3–6 months. Positive prognosticative factors for survival include younger age, high performance scores, and controlled systemic disease. In looking to the future, diagnostics that improve early detection and chemotherapeutics tailored to the primary malignancy will likely be the most significant advances in improving survival.