Transcranial magnetic stimulation and deep brain stimulation have emerged as therapeutic modalities for treatment refractory depression; however, little remains known regarding the circuitry that mediates the therapeutic effect of these approaches. Here we show that direct optogenetic stimulation of prefrontal cortex (PFC) descending projection neurons in mice engineered to express Chr2 in layer V pyramidal neurons (Thy1–Chr2 mice) models an antidepressant-like effect in mice subjected to a forced-swim test. Furthermore, we show that this PFC stimulation induces a long-lasting suppression of anxiety-like behavior (but not conditioned social avoidance) in socially stressed Thy1–Chr2 mice: an effect that is observed >10 d after the last stimulation. Finally, we use optogenetic stimulation and multicircuit recording techniques concurrently in Thy1–Chr2 mice to demonstrate that activation of cortical projection neurons entrains neural oscillatory activity and drives synchrony across limbic brain areas that regulate affect. Importantly, these neural oscillatory changes directly correlate with the temporally precise activation and suppression of limbic unit activity. Together, our findings show that the direct activation of cortical projection systems is sufficient to modulate activity across networks underlying affective regulation. They also suggest that optogenetic stimulation of cortical projection systems may serve as a viable therapeutic strategy for treating affective disorders.

Précis: Intravitreal anti-vascular endothelial growth factor (VEGF) injections may accelerate glaucomatous change in patients with preexisting glaucoma or ocular hypertension (OHT). The safety of long-term injections in this specific population may be reflected in the need for additional glaucoma interventions. Purpose: The purpose of this study was to investigate whether repeated anti-VEGF injections accelerate structural and functional glaucomatous change in eyes with preexisting glaucoma or OHT. Materials and Methods: This is a retrospective, observational study of injected and noninjected fellow eyes. A total of 28 patients with preexisting glaucoma or OHT, who received ≥6 unilateral anti-VEGF injections for concurrent neovascular retinal disease, were selected for chart review. Primary outcome measures were rate of visual field loss in dB/year, rate of change in retinal nerve fiber layer (RNFL) thickness in microns/year, and need for additional glaucoma medications, surgery, or laser. Results: The number of eyes requiring additional glaucoma surgery or laser was 8 of 28 (28.6%) for the injected group and 2 of 28 (7.1%) for the noninjected group. A significantly greater proportion of injected eyes required invasive glaucoma intervention (P=0.034). Average rate of decline in mean deviation and change in pattern standard deviation were both significantly greater in injected eyes (P=0.029; P=0.019). Estimated mean rate of global retinal nerve fiber layer change was −4.27 µm/y for the injected group and −1.17 µm/y for the noninjected group and was significant only for injected eyes (P=0.014). Only the superior quadrant exhibited thinning that was significantly different between groups (P=0.030). Conclusions: Intravitreal injections were associated with accelerated functional and structural glaucoma-like change in susceptible eyes. Clinicians should assess the need for glaucoma medications or other interventions over the course of anti-VEGF therapy.

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History of rhegmatogenous retinal detachment repaired by pars plana vitrectomy with gas tamponade was associated with an increased incidence of pseudophakic after uneventful cataract surgery.