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Early life stress negatively impacts brain development and affects structure and function of parvalbumin immunopositive (PV+) inhibitory neurons. Main regulators of PV+ interneurons activity and plasticity are perineuronal nets (PNNs), an extracellular matrix formation that enwraps PV+ interneurons mainly in the neocortex and hippocampus. To experimentally address the impact of early life stress on the PNNs and PV+ interneurons in the medial prefrontal cortex and dorsal hippocampus in rats, we employed a 24 h maternal deprivation protocol. We show that maternal deprivation in the medial prefrontal cortex of adult rats caused a decrease in density of overall PNNs and PNNs that enwrap PV+ interneurons in the rostral cingulate cortex. Furthermore, a staining intensity decrease of overall PNNs and PNN+/PV+ cells was found in the prelimbic cortex. Finally, a decrease in both intensity and density of overall PNNs and PNNs surrounding PV+ cells was observed in the infralimbic cortex, together with increase in the intensity of VGAT inhibitory puncta. Surprisingly, maternal deprivation did not cause any changes in the density of PV+ interneurons in the mPFC, neither had it affected PNNs and PV+ interneurons in the hippocampus. Taken together, our findings indicate that PNNs, specifically the ones enwrapping PV+ interneurons in the medial prefrontal cortex, are affected by early life stress.
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http://dx.doi.org/10.3389/fcell.2022.982663 | DOI Listing |
Acta Pharmacol Sin
September 2025
Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Bas
Recent investigations into the rapid antidepressant effects of ketamine, along with studies on schizophrenia-related susceptibility genes, have highlighted the GluN2A subunit as a critical regulator of both emotion and cognition. However, the specific impacts of acute pharmacological inhibition of GluN2A-containing NMDA receptors on brain microcircuits and the subsequent behavioral consequences remain poorly understood. In this study, we first examined the effects of MPX-004, a selective GluN2A NMDA receptor inhibitor, on behavior within the dorsomedial prefrontal cortex (dmPFC).
View Article and Find Full Text PDFPLoS Comput Biol
September 2025
Faculty of Science, Cognitive and Systems Neuroscience Group, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands.
Predictive coding (PC) proposes that our brains work as an inference machine, generating an internal model of the world and minimizing predictions errors (i.e., differences between external sensory evidence and internal prediction signals).
View Article and Find Full Text PDFMol Psychiatry
September 2025
Department of Pharmacology, School of Basic Medicine and Department of Pharmacy, Tongji Hospital, Tongji Medical College; and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. chenjg@hu
Dysfunction of parvalbumin-expressing interneurons (PV-INs) in the cerebral cortex has been implicated in major depressive disorder. Perineuronal nets (PNNs), which encapsulate PV-INs, are considered to influence the structural and functional properties of PV-INs. Semaphorin 3A (Sema3A) is a secreted protein constituent of PNNs, but the specific roles of Sema3A in modulating PV-INs during stress remain unknown.
View Article and Find Full Text PDFMol Psychiatry
September 2025
Department of Pharmacological and Biomolecular Sciences "Rodolfo Paoletti", Università degli Studi di Milano, Milan, Italy.
Early-life experiences shape neural networks, with heightened plasticity during the so-called "sensitive periods" (SP). SP are regulated by the maturation of GABAergic parvalbumin-positive (PV+) interneurons, which become enwrapped by perineuronal nets (PNNs) over time, modulating SP closure. Additionally, the opening and closing of SP are orchestrated by two distinct gene clusters known as "trigger" and "brake".
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Institut de Biologie de l'Ecole Normale Supérieure, Ecole Normale Supérieure, Université Paris Sciences et Lettres, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Paris 75005, France.
Excitatory glycine receptors (eGlyRs), composed of the glycine-binding NMDA receptor subunits GluN1 and GluN3A, have recently emerged as a novel neuronal signaling modality that challenges the traditional view of glycine as an inhibitory neurotransmitter. Unlike conventional GluN1/GluN2 NMDARs, the distribution and role of eGlyRs remain poorly understood. Here, we show that eGlyRs are highly enriched in the ventral hippocampus (VH) and confer distinct properties on this brain region.
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