Maternal immune activation alters temporal precision of spike generation of CA1 pyramidal neurons by unbalancing GABAergic inhibition in the Offspring
16 de septiembre de 2024
Te invitamos a leer el artículo: "La activación inmune materna altera la precisión temporal de la generación de picos de las neuronas piramidales CA1 al desequilibrar la inhibición GABAérgica en la descendencia", realizado por el Dr. Emilio J. Galván, Investigador Sede Sur del Cinvestav.
Autores: Ernesto Griego, Camila Cerna, Isabel Sollozo Dupont, Marco Fuenzalida, Emilio J. Galván.
Abstract:
Infection during pregnancy represents a risk factor for neuropsychiatric disorders associated with neurodevelopmental alterations. A growing body of evidence from rodents and non-human primates shows that maternal inflammation induced by viral or bacterial infections results in several neurobiological alterations in the offspring. These changes may play an important role in the pathophysiology of psychiatric disorders like schizophrenia and autism spectrum disorders, whose clinical features include impairments in cognitive processing and social performance. Such alterations are causally associated with the maternal inflammatory response to infection rather than with the infection itself. Previously, we reported that CA1 pyramidal neurons of mice exposed to MIA exhibit increased excitability accompanied by a reduction in dendritic complexity. However, potential alterations in cellular and synaptic rules that shape the neuronal computational properties of the offspring remain to be determined. In this study, using mice as subjects, we identified a series of cellular and synaptic alterations endured by CA1 pyramidal neurons of the dorsal hippocampus in a lipopolysaccharideinduced maternal immune activation (MIA) model. Our data indicate that MIA reshapes the excitationinhibition balance by decreasing the perisomatic GABAergic inhibition predominantly mediated by cholecystokinin-expressing Interneurons but not parvalbumin-expressing interneurons impinging on CA1 pyramidal neurons. These alterations yield a dysregulated amplification of the temporal and spatial synaptic integration. In addition, MIA-exposed offspring displayed social and anxiety-like abnormalities. These findings collectively contribute to understanding the cellular and synaptic alterations underlying the behavioral symptoms present in neurodevelopmental disorders associated with MIA
Keywords:
Maternal immune activation, Hippocampus, CA1 pyramidal cells, Synaptic integration, GABAergic inhibition.