INVESTIGADORES
BELFORTE Juan Emilio
artículos
Título:
Interneuron NMDA receptor ablation induces hippocampus-prefrontal cortex functional hypoconnectivity after adolescence in a mouse model of schizophrenia.
Autor/es:
ALVAREZ, RODRIGO JAVIER; PAFUNDO, DIEGO ESTEBAN; ZOLD, CAMILA; BELFORTE, JUAN EMILIO
Revista:
JOURNAL OF NEUROSCIENCE
Editorial:
SOC NEUROSCIENCE
Referencias:
Lugar: Washington; Año: 2020
ISSN:
0270-6474
Resumen:
Even though the etiology of schizophrenia is still unknown, it is accepted to be a neurodevelopmental25 disorder that results from the interaction of genetic vulnerabilities and environmental insults. Although26 schizophrenia´s pathophysiology is still unclear, postmortem studies point toward a dysfunction of cortical27 interneurons as a central element. It has been suggested that alterations in parvalbumin positive interneurons28 in schizophrenia are the consequence of a deficient signaling through N-methyl-D-aspartate receptors (NMDAr).29 Animal studies demonstrated that early postnatal ablation of the NMDAr in corticolimbic interneurons induces30 neurobiochemical, physiological, behavioral, and epidemiological phenotypes related to schizophrenia. Notably,31 the behavioral abnormalities emerge only after animals complete their maturation during adolescence and are32 absent if the NMDAr is deleted during adulthood. This suggests that interneuron dysfunction must interact with33 development to impact on behavior. Here, we assess in vivo how an early NMDAr ablation in corticolimbic34 interneurons impacts on medial prefrontal cortex (mPFC) and ventral hippocampus (vHP) functional connectivity35 before and after adolescence. In juvenile male mice, NMDAr ablation results in several pathophysiological traits36 including increased cortical activity and decreased entrainment to local gamma and distal hippocampal theta37 rhythms. In addition, adult male KO mice showed reduced vHP-mPFC evoked potentials and an augmented low38 frequency stimulation long-term depression of the pathway suggesting that there is a functional disconnection39 between both structures in adult KO mice. Our results demonstrate that early genetic abnormalities in40 interneurons can interact with postnatal development during adolescence, triggering pathophysiological41 mechanisms related to schizophrenia that exceed those caused by NMDAr interneuron hypofunction alone.