Journal article
Conditional GSK3β deletion in parvalbumin-expressing interneurons potentiates excitatory synaptic function and learning in adult mice
Progress in neuro-psychopharmacology & biological psychiatry, v 100, 109901
08 Jun 2020
PMID: 32113851
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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.
•A triple transgenic mouse with conditional GSK3β deletion in PV interneurons.•GSK3β deletion increases in excitability and synaptic strength in PV interneurons.•GSK3β deletion enhances NMDA functioning in pyramidal neurons in the mPFC.•Physiological changes are associated with facilitated learning.•Novel insight into how GSK3β activity affects PV interneurons and learning.
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Details
- Title
- Conditional GSK3β deletion in parvalbumin-expressing interneurons potentiates excitatory synaptic function and learning in adult mice
- Creators
- Sarah A. Monaco - Drexel UniversityAndrew J. Matamoros - Children's Hospital of PhiladelphiaWen-Jun Gao - Drexel University
- Publication Details
- Progress in neuro-psychopharmacology & biological psychiatry, v 100, 109901
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000522807700005
- Scopus ID
- 2-s2.0-85080971918
- Other Identifier
- 991019167811304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Clinical Neurology
- Neurosciences
- Pharmacology & Pharmacy
- Psychiatry