Latrophilin-3 disruption: Effects on brain and behavior.

• Latrophilins are adhesion G-protein-coupled receptors. • Latrophilin-3 (Lphn3) is a trans-synaptic regulator of synaptic function. • 21 gene variants of LPHN3 are linked to ADHD. • Lphn3 disruption in Drosophila , zebrafish, mice, and rats result in hyperactivity. • Lphn3 KO rats show selective cognitive deficits and dopamine abnormalities. Latrophilin-3 (LPHN3), a G-protein-coupled receptor belonging to the adhesion subfamily, is a regulator of synaptic function and maintenance in brain regions that mediate locomotor activity, attention, and memory for location and path. Variants of LPHN3 are associated with increased risk for attention deficit hyperactivity disorder (ADHD) in some patients. Here we review the role of LPHN3 in the central nervous system (CNS). We describe synaptic localization of LPHN3, its trans-synaptic binding partners, links to neurodevelopmental disorders, animal models of Lphn3 disruption in different species, and evidence that LPHN3 is involved in cognition as well as activity and attention. The evidence shows that LPHN3 plays a more significant role in neuroplasticity than previously appreciated. [ABSTRACT FROM AUTHOR]