Accumulating evidence indicates that non-neuronal cells play critical roles in healthy and aberrant brain function. As examples, microglia, astrocytes, and epithelial cells have been implicated in the etiology of psychiatric illness and considered as potential targets for therapeutics [1, 2]. Assimilation of this knowledge has been slow, especially in light of rapid advances in the development of tools that enable precision regulation of neuronal function, but this may reflect the burden of historic (and increasingly archaic) formulations of brain function. Classic conceptualizations of roles for glial cells, in particular, are derived from the knowledge that “glia” comes from the Greek word for “glue”; indeed, it is often assumed that they play passive roles, serving primarily to provide structure for the brain.

A more comprehensive understanding of how non-neuronal cell types regulate the function of neurons and circuits is needed, particularly in the context of improved use of animal models. There have been major technical advances in the use of approaches such as optogenetics, chemogenetics, and organoids to understand how gene-environment interactions affect brain function and as platforms for drug discovery. To date, these approaches focus predominantly on studies of neuronal function, with few examples where complementary approaches are used to investigate the function of non-neuronal cells. Focusing on neurons seems somewhat analogous to the so-called “streetlight effect”, where research often occurs under conditions that are most pragmatic, despite interpretational risks. If model systems are to fulfill their maximum potential in the study and treatment of neuropsychiatric illness, methods are needed to ensure that neurons and circuits exist within milieus where all other cell subtypes are present and functioning nominally—or at least remain part of the conversation.

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