2026-05-06T02:12:34Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/152262025-03-26T08:23:26Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Sánchez-Castillo, Carla author Cuartero, María I author Fernández-Rodrigo, Alba author Briz, Víctor author López-García, Sergio author Jiménez-Sánchez, Raquel author López, Juan A author Graupera, Mariona author Esteban, José A author Briz, Víctor author 2022-11-25 Neuronal connectivity and activity-dependent synaptic plasticity are fundamental properties that support brain function and cognitive performance. Phosphatidylinositol 3-kinase (PI3K) intracellular signaling controls multiple mechanisms mediating neuronal growth, synaptic structure, and plasticity. However, it is still unclear how these pleiotropic functions are integrated at molecular and cellular levels. To address this issue, we used neuron-specific virally delivered Cre expression to delete either p110α or p110β (the two major catalytic isoforms of type I PI3K) from the hippocampus of adult mice. We found that dendritic and postsynaptic structures are almost exclusively supported by p110α activity, whereas p110β controls neurotransmitter release and metabotropic glutamate receptor-dependent long-term depression at the presynaptic terminal. In addition to these separate functions, p110α and p110β jointly contribute to N-methyl-d-aspartate receptor-dependent postsynaptic long-term potentiation. This molecular and functional specialization is reflected in different proteomes controlled by each isoform and in distinct behavioral alterations for learning/memory and sociability in mice lacking p110α or p110β. Sci Adv. 2022 Nov 25;8(47):eabq8109. 10.1126/sciadv.abq8109 2375-2548 Science advances 36417513 http://hdl.handle.net/20.500.12105/15226 Functional specialization of different PI3K isoforms for the control of neuronal architecture, synaptic plasticity, and cognition.