Glycogen synthase kinase 3β (GSK3β) has gained interest regarding its involvement in psychiatric and neurodegenerative disorders. Recently GSK3 inhibitors were highlighted as promising rescuers of cognitive impairments for a gamut of CNS disorders. Growing evidence supports that fast-spiking parvalbumin (PV) interneurons are critical regulators of cortical computation. Albeit, how excitatory receptors on PV interneurons are regulated and how this affects cognitive function remains unknown. To address these questions, we have generated a novel triple-transgenic conditional mouse with GSK3β genetically deleted from PV interneurons. PV-GSK3β resulted in increased excitability and augmented excitatory synaptic strength in prefrontal PV interneurons. More importantly, these synaptic changes are correlated with accelerated learning with no changes in locomotion and sociability. Our study, for the first time, examined how GSK3β activity affects learning capability via regulation of PV interneurons. This study provides a novel insight into how GSK3β may contribute to disorders afflicted by cognitive deficits.
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http://dx.doi.org/10.1016/j.pnpbp.2020.109901 | DOI Listing |
ACS Appl Mater Interfaces
January 2025
School of Information Science and Technology, Fudan University, Shanghai 200433, China.
To date, various kinds of memristors have been proposed as artificial neurons and synapses for neuromorphic computing to overcome the so-called von Neumann bottleneck in conventional computing architectures. However, related working principles are mostly ascribed to randomly distributed conductive filaments or traps, which usually lead to high stochasticity and poor uniformity. In this work, a heterostructure with a two-dimensional WS monolayer and a ferroelectric PZT film were demonstrated for memristors and artificial synapses, triggered by in-plane ferroelectric polarization.
View Article and Find Full Text PDFCell Rep
January 2025
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea; Neuroscience Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South Korea; Transplantation Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South Korea. Electronic address:
Cd99 molecule-like 2 (Cd99l2) is a type I transmembrane protein that plays a role in the transmigration of leukocytes across vascular endothelial cells. Despite its high expression in the brain, the role of Cd99l2 remains elusive. We find that Cd99l2 is expressed primarily in neurons and positively regulates neurite outgrowth and the development of excitatory synapses.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.
The orbitofrontal cortex (OFC) is a large cortical structure, expansive across anterior-posterior axes. It is essential for flexibly updating learned behaviors, and paradoxically, also implicated in inflexible and compulsive-like behaviors. Here, we investigated mice bred to display inflexible reward-seeking behaviors that are insensitive to action consequences.
View Article and Find Full Text PDFPLoS Genet
January 2025
Department of Psychology, University of Texas at Austin, Austin, Texas, United States of America.
Social hierarchies are a common form of social organization across species. Although hierarchies are largely stable across time, animals may socially ascend or descend within hierarchies depending on environmental and social challenges. Here, we develop a novel paradigm to study social ascent and descent within male CD-1 mouse social hierarchies.
View Article and Find Full Text PDFBiological memory networks are thought to store information by experience-dependent changes in the synaptic connectivity between assemblies of neurons. Recent models suggest that these assemblies contain both excitatory and inhibitory neurons (E/I assemblies), resulting in co-tuning and precise balance of excitation and inhibition. To understand computational consequences of E/I assemblies under biologically realistic constraints we built a spiking network model based on experimental data from telencephalic area Dp of adult zebrafish, a precisely balanced recurrent network homologous to piriform cortex.
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