Layers II/III of Prefrontal Cortex in Df(h22q11)/+ Mouse Model of the 22q11.2 Deletion Display Loss of Parvalbumin Inter
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ORIGINAL ARTICLE
Layers II/III of Prefrontal Cortex in Df(h22q11)/+ Mouse Model of the 22q11.2 Deletion Display Loss of Parvalbumin Interneurons and Modulation of Neuronal Morphology and Excitability Abdel-Rahman Al-Absi 1 & Per Qvist 2,3,4,5 & Samora Okujeni 6 & Ahmad Raza Khan 7,8 & Simon Glerup 2 & Connie Sanchez 9 & Jens R. Nyengaard 1 Received: 19 May 2020 / Accepted: 9 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The 22q11.2 deletion has been identified as a risk factor for multiple neurodevelopmental disorders. Behavioral and cognitive impairments are common among carriers of the 22q11.2 deletion. Parvalbumin expressing (PV+) interneurons provide perisomatic inhibition of excitatory neuronal circuits through GABAA receptors, and a deficit of PV+ inhibitory circuits may underlie a multitude of the behavioral and functional deficits in the 22q11.2 deletion syndrome. We investigated putative deficits of PV+ inhibitory circuits and the associated molecular, morphological, and functional alterations in the prefrontal cortex (PFC) of the Df(h22q11)/+ mouse model of the 22q11.2 hemizygous deletion. We detected a significant decrease in the number of PV+ interneurons in layers II/III of PFC in Df(h22q11)/+ mice together with a reduction in the mRNA and protein levels of GABAA (α3), a PV+ putative postsynaptic receptor subunit. Pyramidal neurons from the same layers further experienced morphological reorganizations of spines and dendrites. Accordingly, a decrease in the levels of the postsynaptic density protein 95 (PSD95) and a higher neuronal activity in response to the GABAA antagonist bicuculline were measured in these layers in PFC of Df(h22q11)/+ mice compared with their wild-type littermates. Our study shows that a hemizygotic deletion of the 22q11.2 locus leads to deficit in the GABAergic control of network activity and involves molecular and morphological changes in both the inhibitory and excitatory synapses of parvalbumin interneurons and pyramidal neurons specifically in layers II/III PFC. Keywords Df(h22q11)/+ mouse model . Prefrontal cortex . Parvalbumin interneurons . GABAA (α3)receptorsubunit . Pyramidal neurons
Introduction The 22q11.2 deletion is a genetic condition that involves 1.5– 3 M bases encompassing 30–50 genes and has an approximate
prevalence of 1 in 3000–4000 live births [1]. This deletion represents the highest known individual genetic risk factor for the emergence of schizophrenia [2], and it confers high risk for other neurodevelopmental disorders [3]. Carriers of
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12035-020-02067-1) contains supplementary material, which is available to authorized users. * Abdel-Rahman Al-Absi [email protected] Per Qvist [email protected] Samora Okujeni [email protected] Ahmad Raza Khan [email protected]
Simon Glerup [email protected] Connie Sanchez [email protected] Jens R. Nyengaard [email protected] Extended a
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