Spatiotemporal analysis of gene expression in the human dentate gyrus reveals age-associated changes in cellular maturation and neuroinflammation.

The dentate gyrus of the hippocampus is important for many cognitive functions, including learning, memory, and mood. Here, we investigated age-associated changes in transcriptome-wide spatial gene expression in the human dentate gyrus across the lifespan. Genes associated with neurogenesis and the extracellular matrix were enriched in infants, while gene markers of inhibitory neurons and cell proliferation showed increases and decreases in post-infancy, respectively.

CB antagonism increases excitatory synaptogenesis in a cortical spheroid model of fetal brain development.

The endocannabinoid system (ECS) plays a complex role in the development of neural circuitry during fetal brain development. The cannabinoid receptor type 1 (CB) controls synaptic strength at both excitatory and inhibitory synapses and thus contributes to the balance of excitatory and inhibitory signaling. Imbalances in the ratio of excitatory to inhibitory synapses have been implicated in various neuropsychiatric disorders associated with dysregulated central nervous system development including autism spectrum disorder, epilepsy, and schizophrenia.

Human-Derived Brain Models: Windows into Neuropsychiatric Disorders and Drug Therapies.

Human-derived neurons and brain organoids have revolutionized our ability to model brain development in a dish. In this review, we discuss the potential for human brain models to advance drug discovery for complex neuropsychiatric disorders. First, we address the advantages of human brain models to screen for new drugs capable of altering CNS activity.