Studies suggest that abnormalities in glutamate and GABA signaling contribute to deficits in schizophrenia and related conditions and that these neurochemical abnormalities produce changes in electroencephalographic (EEG) indices, including event-related potentials and event-related power within specific frequency ranges. Furthermore, clinical studies suggest that a subset of EEG biomarkers is associated with symptoms. This review addresses the relationship between EEG and behavior in preclinical models of N-methyl-d-aspartate (NMDA)-receptor hypofunction, as well as how these models can be used to screen therapies. Data from schizophrenia patients are juxtaposed with data from animal models, and EEG and behavioral data from mice with disruption of NMDA receptors in excitatory and/or inhibitory neurons are then compared to the pattern observed in schizophrenia. Also discussed are results following exposure to potential therapeutic agents, including GABAB agonists. Furthermore, evidence demonstrates that elevated resting gamma power is associated with deficits in social interactions. Consistent with elevated baseline noise, excitatory neurons from transgenic mice show increased intrinsic excitability in in vitro-slice patch-clamp studies across model systems. GABAB receptor agonists reduce this excitability, improve gamma-band responses, and reverse behavioral deficits in mice. Data suggest that baseline gamma power is associated with social function and GABAB agonists may be useful for schizophrenia. Translational EEG biomarkers reflect target engagement and can contribute to the design of more efficient drug trials, likely accelerating the development of new therapeutics for central nervous system disorders.

The activity and survival of retinal photoreceptors depend on support functions performed by the retinal pigment epithelium (RPE) and on oxygen and nutrients delivered by blood vessels in the underlying choroid. By combining single-cell and bulk RNA sequencing, we categorized mouse RPE/choroid cell types and characterized the tissue-specific transcriptomic features of choroidal endothelial cells. We found that choroidal endothelium adjacent to the RPE expresses high levels of Indian Hedgehog and identified its downstream target as stromal GLI1+ mesenchymal stem cell–like cells. In vivo genetic impairment of Hedgehog signaling induced significant loss of choroidal mast cells, as well as an altered inflammatory response and exacerbated visual function defects after retinal damage. Our studies reveal the cellular and molecular landscape of adult RPE/choroid and uncover a Hedgehog-regulated choroidal immunomodulatory signaling circuit. These results open new avenues for the study and treatment of retinal vascular diseases and choroid-related inflammatory blinding disorders.